Brief Summary
Adavosertib in combination with carboplatin, paclitaxel, gemcitabine, or PLD.
Brief Title
Adavosertib Plus Chemotherapy in Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Detailed Description
This is an open-label, four-arm lead-in safety and efficacy study in which adavosertib will be combined in four separate treatment arms as follows: adavosertib plus gemcitabine (Arm A); adavosertib plus weekly paclitaxel (Arm B); adavosertib plus carboplatin (Arm C); and adavosertib plus PLD (Arm D). A subset of patients will be evaluated for the safety assessment of each treatment arm.
The adavosertib plus paclitaxel arm (Arm B) will enrol approximately 30 additional patients at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.
In addition, the adavosertib plus carboplatin arm (Arm C) will enrol approximately 23 patients overall at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.
To further optimise the dosing schedule of adavosertib in Arm C, a safety expansion arm (referred to as Arm C2) of approximately 12 additional patients will be enrolled at selected sites to explore emerging pre-clinical and clinical data that suggest that prolonged adavosertib exposure may increase the clinical activity.
The adavosertib plus paclitaxel arm (Arm B) will enrol approximately 30 additional patients at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.
In addition, the adavosertib plus carboplatin arm (Arm C) will enrol approximately 23 patients overall at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.
To further optimise the dosing schedule of adavosertib in Arm C, a safety expansion arm (referred to as Arm C2) of approximately 12 additional patients will be enrolled at selected sites to explore emerging pre-clinical and clinical data that suggest that prolonged adavosertib exposure may increase the clinical activity.
Completion Date
Completion Date Type
Actual
Conditions
Ovarian, Fallopian Tube, Peritoneal Cancer, P53 Mutation
Eligibility Criteria
Inclusion
* Has read and understands the informed consent form (ICF) and has given written IC prior to any study specific procedures.
* Histologic or cytologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer.
* Progressed within 6 months of completing at least 4 cycles of a first-line platinum-containing regimen for Stage III/IV disease. Patients with refractory disease (progression during platinum-containing therapy) are ineligible.
* No more than 2-4 prior treatment regimens for Stage III/IV disease, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy.
* Prior doxorubicin (or other anthracycline) at a cumulative dose of ≤ 360 mg/m² or cumulative epirubicin dose of ≤ 720 mg/m² (calculated using doxorubicin equivalent doses: 1 mg of doxorubicin = 1 mg PLD = 0.3 mg mitoxantrone = 0.25 mg idarubicin). Subjects without any prior anthracycline exposure can also be included. Applies to Arm D only.
* At least 1 measurable lesion according to RECIST v1.1.
* Any prior palliative radiation therapy must be completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects prior to start of study treatment.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 - 1.
* Baseline Laboratory Values:
1. ANC ≥1500/μL
2. HgB ≥ 9 g/dL with no blood transfusions in the past 28 days
3. Platelets ≥ 100,000/μL
4. ALT \& AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases
5. Serum bilirubin within normal limits (WNL) or ≤1.5 x the ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
6. Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method.
* Left ventricular ejection fraction (LVEF) WNL of the institution as determined by multiple uptake gated acquisition (MUGA) or echocardiography (ECHO) (applies to Arm D only).
* Female patients, ≥18, (not of childbearing potential and fertile female patients of childbearing potential) who agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after study treatment discontinuation, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start.
* Predicted life expectancy ≥ 12 weeks
Exclusion
* Use of a study drug (approved or investigational drug therapy) ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required.
* Major surgical procedures ≤ 28 days of beginning study, or minor surgical procedures ≤ 7 days. No waiting period following port-a-cath placement, or any other central venous access placement.
* Grade \>1 toxicity from prior therapy (except alopecia or anorexia).
* Known malignant CNS disease other than neurologically stable, treated brain metastases, defined as metastasis having no evidence of progression or haemorrhage after treatment for at least 2 weeks (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment.
* Patient has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after last dose of study drug.
* Caution should be exercised when inhibitors or substrates of P-gP, substrates of CYP1A2 with a narrow therapeutic range, sensitive substrates of CYP2C19 or CYP2C19 substrates with a narrow therapeutic range are administered with adavosertib.
* Herbal medications should be discontinued 7 days prior to the first dose of study treatment.
* Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2:
1. Unstable angina pectoris
2. Congestive heart failure
3. Acute myocardial infarction
4. Conduction abnormality not controlled with pacemaker or medication
5. Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
* Adavosertib should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. Adavosertib has not been studied in patients with ventricular arrhythmias or recent myocardial infarction.
* Corrected QT interval (QTc) \>470 msec at study entry or congenital long QT syndrome.
* Pregnant or lactating.
* Serious active infection at the time of enrolment, or another serious underlying medical condition that would impair the patient's ability to receive study treatment.
* Presence of other active cancers, or history of treatment for invasive cancer within 3 years. Patients with Stage I cancer who have received definitive local treatment within 3 years, and whom are considered unlikely to recur, are eligible. Patients with previously treated in-situ carcinoma (i.e., non-invasive) are eligible, as are patients with prior non-melanoma skin cancers.
* Has read and understands the informed consent form (ICF) and has given written IC prior to any study specific procedures.
* Histologic or cytologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer.
* Progressed within 6 months of completing at least 4 cycles of a first-line platinum-containing regimen for Stage III/IV disease. Patients with refractory disease (progression during platinum-containing therapy) are ineligible.
* No more than 2-4 prior treatment regimens for Stage III/IV disease, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy.
* Prior doxorubicin (or other anthracycline) at a cumulative dose of ≤ 360 mg/m² or cumulative epirubicin dose of ≤ 720 mg/m² (calculated using doxorubicin equivalent doses: 1 mg of doxorubicin = 1 mg PLD = 0.3 mg mitoxantrone = 0.25 mg idarubicin). Subjects without any prior anthracycline exposure can also be included. Applies to Arm D only.
* At least 1 measurable lesion according to RECIST v1.1.
* Any prior palliative radiation therapy must be completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects prior to start of study treatment.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 - 1.
* Baseline Laboratory Values:
1. ANC ≥1500/μL
2. HgB ≥ 9 g/dL with no blood transfusions in the past 28 days
3. Platelets ≥ 100,000/μL
4. ALT \& AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases
5. Serum bilirubin within normal limits (WNL) or ≤1.5 x the ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
6. Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method.
* Left ventricular ejection fraction (LVEF) WNL of the institution as determined by multiple uptake gated acquisition (MUGA) or echocardiography (ECHO) (applies to Arm D only).
* Female patients, ≥18, (not of childbearing potential and fertile female patients of childbearing potential) who agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after study treatment discontinuation, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start.
* Predicted life expectancy ≥ 12 weeks
Exclusion
* Use of a study drug (approved or investigational drug therapy) ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required.
* Major surgical procedures ≤ 28 days of beginning study, or minor surgical procedures ≤ 7 days. No waiting period following port-a-cath placement, or any other central venous access placement.
* Grade \>1 toxicity from prior therapy (except alopecia or anorexia).
* Known malignant CNS disease other than neurologically stable, treated brain metastases, defined as metastasis having no evidence of progression or haemorrhage after treatment for at least 2 weeks (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment.
* Patient has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after last dose of study drug.
* Caution should be exercised when inhibitors or substrates of P-gP, substrates of CYP1A2 with a narrow therapeutic range, sensitive substrates of CYP2C19 or CYP2C19 substrates with a narrow therapeutic range are administered with adavosertib.
* Herbal medications should be discontinued 7 days prior to the first dose of study treatment.
* Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2:
1. Unstable angina pectoris
2. Congestive heart failure
3. Acute myocardial infarction
4. Conduction abnormality not controlled with pacemaker or medication
5. Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
* Adavosertib should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. Adavosertib has not been studied in patients with ventricular arrhythmias or recent myocardial infarction.
* Corrected QT interval (QTc) \>470 msec at study entry or congenital long QT syndrome.
* Pregnant or lactating.
* Serious active infection at the time of enrolment, or another serious underlying medical condition that would impair the patient's ability to receive study treatment.
* Presence of other active cancers, or history of treatment for invasive cancer within 3 years. Patients with Stage I cancer who have received definitive local treatment within 3 years, and whom are considered unlikely to recur, are eligible. Patients with previously treated in-situ carcinoma (i.e., non-invasive) are eligible, as are patients with prior non-melanoma skin cancers.
Inclusion Criteria
Inclusion
* Has read and understands the informed consent form (ICF) and has given written IC prior to any study specific procedures.
* Histologic or cytologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer.
* Progressed within 6 months of completing at least 4 cycles of a first-line platinum-containing regimen for Stage III/IV disease. Patients with refractory disease (progression during platinum-containing therapy) are ineligible.
* No more than 2-4 prior treatment regimens for Stage III/IV disease, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy.
* Prior doxorubicin (or other anthracycline) at a cumulative dose of ≤ 360 mg/m² or cumulative epirubicin dose of ≤ 720 mg/m² (calculated using doxorubicin equivalent doses: 1 mg of doxorubicin = 1 mg PLD = 0.3 mg mitoxantrone = 0.25 mg idarubicin). Subjects without any prior anthracycline exposure can also be included. Applies to Arm D only.
* At least 1 measurable lesion according to RECIST v1.1.
* Any prior palliative radiation therapy must be completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects prior to start of study treatment.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 - 1.
* Baseline Laboratory Values:
1. ANC ≥1500/μL
2. HgB ≥ 9 g/dL with no blood transfusions in the past 28 days
3. Platelets ≥ 100,000/μL
4. ALT \& AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases
5. Serum bilirubin within normal limits (WNL) or ≤1.5 x the ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
6. Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method.
* Left ventricular ejection fraction (LVEF) WNL of the institution as determined by multiple uptake gated acquisition (MUGA) or echocardiography (ECHO) (applies to Arm D only).
* Female patients, ≥18, (not of childbearing potential and fertile female patients of childbearing potential) who agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after study treatment discontinuation, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start.
* Predicted life expectancy ≥ 12 weeks
Exclusion
* Use of a study drug (approved or investigational drug therapy) ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required.
* Major surgical procedures ≤ 28 days of beginning study, or minor surgical procedures ≤ 7 days. No waiting period following port-a-cath placement, or any other central venous access placement.
* Grade \>1 toxicity from prior therapy (except alopecia or anorexia).
* Known malignant CNS disease other than neurologically stable, treated brain metastases, defined as metastasis having no evidence of progression or haemorrhage after treatment for at least 2 weeks (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment.
* Patient has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after last dose of study drug.
* Caution should be exercised when inhibitors or substrates of P-gP, substrates of CYP1A2 with a narrow therapeutic range, sensitive substrates of CYP2C19 or CYP2C19 substrates with a narrow therapeutic range are administered with adavosertib.
* Herbal medications should be discontinued 7 days prior to the first dose of study treatment.
* Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2:
1. Unstable angina pectoris
2. Congestive heart failure
3. Acute myocardial infarction
4. Conduction abnormality not controlled with pacemaker or medication
5. Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
* Adavosertib should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. Adavosertib has not been studied in patients with ventricular arrhythmias or recent myocardial infarction.
* Corrected QT interval (QTc) \>470 msec at study entry or congenital long QT syndrome.
* Pregnant or lactating.
* Serious active infection at the time of enrolment, or another serious underlying medical condition that would impair the patient's ability to receive study treatment.
* Presence of other active cancers, or history of treatment for invasive cancer within 3 years. Patients with Stage I cancer who have received definitive local treatment within 3 years, and whom are considered unlikely to recur, are eligible. Patients with previously treated in-situ carcinoma (i.e., non-invasive) are eligible, as are patients with prior non-melanoma skin cancers.
* Has read and understands the informed consent form (ICF) and has given written IC prior to any study specific procedures.
* Histologic or cytologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer.
* Progressed within 6 months of completing at least 4 cycles of a first-line platinum-containing regimen for Stage III/IV disease. Patients with refractory disease (progression during platinum-containing therapy) are ineligible.
* No more than 2-4 prior treatment regimens for Stage III/IV disease, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy.
* Prior doxorubicin (or other anthracycline) at a cumulative dose of ≤ 360 mg/m² or cumulative epirubicin dose of ≤ 720 mg/m² (calculated using doxorubicin equivalent doses: 1 mg of doxorubicin = 1 mg PLD = 0.3 mg mitoxantrone = 0.25 mg idarubicin). Subjects without any prior anthracycline exposure can also be included. Applies to Arm D only.
* At least 1 measurable lesion according to RECIST v1.1.
* Any prior palliative radiation therapy must be completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects prior to start of study treatment.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 - 1.
* Baseline Laboratory Values:
1. ANC ≥1500/μL
2. HgB ≥ 9 g/dL with no blood transfusions in the past 28 days
3. Platelets ≥ 100,000/μL
4. ALT \& AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases
5. Serum bilirubin within normal limits (WNL) or ≤1.5 x the ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
6. Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method.
* Left ventricular ejection fraction (LVEF) WNL of the institution as determined by multiple uptake gated acquisition (MUGA) or echocardiography (ECHO) (applies to Arm D only).
* Female patients, ≥18, (not of childbearing potential and fertile female patients of childbearing potential) who agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after study treatment discontinuation, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start.
* Predicted life expectancy ≥ 12 weeks
Exclusion
* Use of a study drug (approved or investigational drug therapy) ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required.
* Major surgical procedures ≤ 28 days of beginning study, or minor surgical procedures ≤ 7 days. No waiting period following port-a-cath placement, or any other central venous access placement.
* Grade \>1 toxicity from prior therapy (except alopecia or anorexia).
* Known malignant CNS disease other than neurologically stable, treated brain metastases, defined as metastasis having no evidence of progression or haemorrhage after treatment for at least 2 weeks (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment.
* Patient has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after last dose of study drug.
* Caution should be exercised when inhibitors or substrates of P-gP, substrates of CYP1A2 with a narrow therapeutic range, sensitive substrates of CYP2C19 or CYP2C19 substrates with a narrow therapeutic range are administered with adavosertib.
* Herbal medications should be discontinued 7 days prior to the first dose of study treatment.
* Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2:
1. Unstable angina pectoris
2. Congestive heart failure
3. Acute myocardial infarction
4. Conduction abnormality not controlled with pacemaker or medication
5. Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
* Adavosertib should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. Adavosertib has not been studied in patients with ventricular arrhythmias or recent myocardial infarction.
* Corrected QT interval (QTc) \>470 msec at study entry or congenital long QT syndrome.
* Pregnant or lactating.
* Serious active infection at the time of enrolment, or another serious underlying medical condition that would impair the patient's ability to receive study treatment.
* Presence of other active cancers, or history of treatment for invasive cancer within 3 years. Patients with Stage I cancer who have received definitive local treatment within 3 years, and whom are considered unlikely to recur, are eligible. Patients with previously treated in-situ carcinoma (i.e., non-invasive) are eligible, as are patients with prior non-melanoma skin cancers.
Gender
Female
Gender Based
false
Keywords
Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
130 Years
Minimum Age
18 Years
NCT Id
NCT02272790
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D6010C00004
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Multicentre Phase II Study of Adavosertib Plus Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Primary Outcomes
Outcome Description
Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria.
Outcome Measure
Objective Response Rate (ORR)
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Secondary Ids
Secondary Id
GYN 49
Secondary Id
2015-000886-30
Secondary Outcomes
Outcome Description
The Disease Control Rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria.
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
Disease Control Rate (DCR)
Outcome Description
Duration of Response (DoR) is defined as the time from first documented tumour response until the date of documented progression or death from any cause.
Outcome Time Frame
Throughout the duration of the study, approximately 19 months.
Outcome Measure
Duration of Response (DoR)
Outcome Description
Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.
Progression-free survival was derived based on scan/assessment dates, not visit dates.
Progression-free survival was derived based on scan/assessment dates, not visit dates.
Outcome Time Frame
Throughout the Study, Approximately 4 years
Outcome Measure
Progression Free Survival (Median, 80% CI)
Outcome Description
Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.
Progression-free survival was derived based on scan/assessment dates, not visit dates.
Progression-free survival was derived based on scan/assessment dates, not visit dates.
Outcome Time Frame
Throughout the Study, Approximately 4 years
Outcome Measure
Progression Free Survival (Median, 95% CI)
Outcome Description
Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.
Outcome Time Frame
Throughout the Study, Approximately 4 years
Outcome Measure
Overall Survival (Median, 80% CI)
Outcome Description
Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.
Outcome Time Frame
Throughout the Study, Approximately 4 years
Outcome Measure
Overall Survival (Median, 95% CI)
Outcome Description
The GCIG CA-125 response is defined as the proportion of patients achieving a 50% reduction in CA-125 levels from baseline, if baseline level is ≥2 x the upper limit of normal (ULN) within 2 weeks prior to starting treatment. Response must be confirmed and maintained for at least 28 days.
Outcome Time Frame
Throughout the study, approximately 4 years
Outcome Measure
Gynecologic Cancer Intergroup (GCIG) CA-125 Response
Outcome Description
The number of patients experiencing at least one treatment-related adverse event (TEAE) by maximum CTCAE grade.
Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.
Outcome Description
The number and proportion of patients experiencing at least one treatment-related adverse event (TEAE) related to adavosertib by maximum CTCAE grade
Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade
Outcome Description
The number of patients experiencing at least one treatment-related adverse event (TEAE) related to chemotherapy by maximum CTCAE grade.
Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade
Outcome Description
The number of patients experiencing at least one serious adverse event (SAE).
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
Serious Adverse Events
Outcome Description
The number of patients experiencing at least one serious adverse event (SAE) leading to death.
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
Serious Adverse Events Leading to Death
Outcome Description
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment discontinuation.
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation
Outcome Description
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to dose reduction.
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction
Outcome Description
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment interruption.
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption
Outcome Description
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment discontinuation.
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation
Outcome Description
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to dose reduction.
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction
Outcome Description
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment interruption.
Outcome Time Frame
Throughout the duration of the study (up to 19 months)
Outcome Measure
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption
Outcome Description
Maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.
Outcome Time Frame
Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Outcome Measure
Single Dose Adavosertib Cmax
Outcome Description
Maximum plasma concentration of adavosertib after a multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.
Outcome Time Frame
Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Outcome Measure
Multiple Dose Adavosertib Cmax
Outcome Description
The time to reach maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.
Outcome Time Frame
Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Outcome Measure
Single Dose Adavosertib Tmax
Outcome Description
The time to reach maximum plasma concentration of adavosertib after multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.
Outcome Time Frame
Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Outcome Measure
Multiple Dose Adavosertib Tmax
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
130
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Gloria Huang
Investigator Email
ghuang@montefiore.org
Investigator Phone
718-405-8082
MeSH Terms
ADAVOSERTIB
PACLITAXEL
CARBOPLATIN
GEMCITABINE
1-DODECYLPYRIDOXAL
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
DITERPENES
TERPENES
COORDINATION COMPLEXES
HETEROCYCLIC COMPOUNDS
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING