Brief Summary
This phase II trial studies how well radiation therapy, paclitaxel, and carboplatin work in treating patients with high-risk endometrial cancer. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Giving radiation therapy with chemotherapy may kill more tumor cells.
Brief Title
Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With High-Risk Endometrial Cancer
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate progression-free survival. II. To assess and document location of disease recurrence (distant vs local vs both) using this treatment regimen.
II. To evaluate the toxicity of radiation therapy "sandwiched" between cycles of paclitaxel/carboplatin chemotherapy in patients with high-risk endometrial cancer.
III. To evaluate the associations of cancer recurrence with tumor tissue expression levels of insulin-like growth factor-I (IGF-I), IGF-II, insulin-like growth factor binding protein 1 (IGFBP-1) and -3, insulin receptor, IGF-I receptor, estrogen receptor, and progesterone receptor.
OUTLINE:
CHEMOTHERAPY (weeks 1-9, 13-21): Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 courses during weeks 1-9 and 3 courses during weeks 13-21.
RADIATION THERAPY (weeks 8-13 or 8-15): Patients with stage I disease undergo high dose rate (HDR) brachytherapy once weekly for a total of 5 fractions during weeks 8-13. All other patients undergo external beam radiation therapy (EBRT) once daily (QD) 5 days a week for a total of 25 fractions during weeks 8-12 and HDR brachytherapy once weekly for a total of 3 fractions during weeks 13-15.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
I. To evaluate progression-free survival. II. To assess and document location of disease recurrence (distant vs local vs both) using this treatment regimen.
II. To evaluate the toxicity of radiation therapy "sandwiched" between cycles of paclitaxel/carboplatin chemotherapy in patients with high-risk endometrial cancer.
III. To evaluate the associations of cancer recurrence with tumor tissue expression levels of insulin-like growth factor-I (IGF-I), IGF-II, insulin-like growth factor binding protein 1 (IGFBP-1) and -3, insulin receptor, IGF-I receptor, estrogen receptor, and progesterone receptor.
OUTLINE:
CHEMOTHERAPY (weeks 1-9, 13-21): Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 courses during weeks 1-9 and 3 courses during weeks 13-21.
RADIATION THERAPY (weeks 8-13 or 8-15): Patients with stage I disease undergo high dose rate (HDR) brachytherapy once weekly for a total of 5 fractions during weeks 8-13. All other patients undergo external beam radiation therapy (EBRT) once daily (QD) 5 days a week for a total of 25 fractions during weeks 8-12 and HDR brachytherapy once weekly for a total of 3 fractions during weeks 13-15.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Completion Date
Completion Date Type
Actual
Conditions
Endometrial Adenocarcinoma
Stage IA Uterine Corpus Cancer
Stage IB Uterine Corpus Cancer
Stage II Uterine Corpus Cancer
Stage IIIA Uterine Corpus Cancer
Stage IIIB Uterine Corpus Cancer
Stage IIIC Uterine Corpus Cancer
Stage IVA Uterine Corpus Cancer
Stage IVB Uterine Corpus Cancer
Eligibility Criteria
Inclusion Criteria:
* Histologically-documented high-risk endometrioid adenocarcinoma with no visible residual disease, defined by the following criteria:
* Surgical stage I disease with \< 50 myometrial invasion and grade 3 tumor (IAG3) with lymphovascular space involvement;
* Surgical stage I disease with \>= 50% myometrial invasion and grade 2 or 3 tumor (IBG2, IBG3);
* Any surgical stage II disease (II);
* Any surgical stage III disease (IIIA, IIIB, IIIC); and
* Any surgical stage IV disease with no residual macroscopic tumor
* Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node samplings as per standard Gynecologic Oncology Group (GOG) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of \< 2
* Written voluntary informed consent
Exclusion Criteria:
* Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) \> 2.5 times the institutional upper limit of normal
* Total serum bilirubin \> 1.5 mg/dl
* History of chronic or active hepatitis
* Serum creatinine \> 2.0 mg/dl
* Platelets \< 100,000/mm\^3
* Absolute neutrophil count (ANC) \< 1500/mm\^3
* Hemoglobin \< 8.0 g/dl (the patient may be transfused prior to study entry)
* Patient has severe or uncontrolled concurrent medical disease (e.g. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)
* Patient with any prior chemotherapy or radiotherapy for pelvic malignancy
* Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at the time of study entry
* Patients with any history of cancer with the exception of non-melanoma skin cancer are excluded if there is any evidence of other malignancy being present within the past five years
* Histologically-documented high-risk endometrioid adenocarcinoma with no visible residual disease, defined by the following criteria:
* Surgical stage I disease with \< 50 myometrial invasion and grade 3 tumor (IAG3) with lymphovascular space involvement;
* Surgical stage I disease with \>= 50% myometrial invasion and grade 2 or 3 tumor (IBG2, IBG3);
* Any surgical stage II disease (II);
* Any surgical stage III disease (IIIA, IIIB, IIIC); and
* Any surgical stage IV disease with no residual macroscopic tumor
* Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node samplings as per standard Gynecologic Oncology Group (GOG) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of \< 2
* Written voluntary informed consent
Exclusion Criteria:
* Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) \> 2.5 times the institutional upper limit of normal
* Total serum bilirubin \> 1.5 mg/dl
* History of chronic or active hepatitis
* Serum creatinine \> 2.0 mg/dl
* Platelets \< 100,000/mm\^3
* Absolute neutrophil count (ANC) \< 1500/mm\^3
* Hemoglobin \< 8.0 g/dl (the patient may be transfused prior to study entry)
* Patient has severe or uncontrolled concurrent medical disease (e.g. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)
* Patient with any prior chemotherapy or radiotherapy for pelvic malignancy
* Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at the time of study entry
* Patients with any history of cancer with the exception of non-melanoma skin cancer are excluded if there is any evidence of other malignancy being present within the past five years
Inclusion Criteria
Inclusion Criteria:
* Histologically-documented high-risk endometrioid adenocarcinoma with no visible residual disease, defined by the following criteria:
* Surgical stage I disease with \< 50 myometrial invasion and grade 3 tumor (IAG3) with lymphovascular space involvement;
* Surgical stage I disease with \>= 50% myometrial invasion and grade 2 or 3 tumor (IBG2, IBG3);
* Any surgical stage II disease (II);
* Any surgical stage III disease (IIIA, IIIB, IIIC); and
* Any surgical stage IV disease with no residual macroscopic tumor
* Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node samplings as per standard Gynecologic Oncology Group (GOG) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of \< 2
* Written voluntary informed consent
* Histologically-documented high-risk endometrioid adenocarcinoma with no visible residual disease, defined by the following criteria:
* Surgical stage I disease with \< 50 myometrial invasion and grade 3 tumor (IAG3) with lymphovascular space involvement;
* Surgical stage I disease with \>= 50% myometrial invasion and grade 2 or 3 tumor (IBG2, IBG3);
* Any surgical stage II disease (II);
* Any surgical stage III disease (IIIA, IIIB, IIIC); and
* Any surgical stage IV disease with no residual macroscopic tumor
* Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node samplings as per standard Gynecologic Oncology Group (GOG) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of \< 2
* Written voluntary informed consent
Gender
Female
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01041027
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
08-03-060
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Pilot Phase II Trial of Radiation Therapy "Sandwiched" Between Paclitaxel and Carboplatin in Patients With High-Risk Endometrial Cancer After Standard Surgical Staging
Primary Outcomes
Outcome Description
PFS will be analyzed using standard survival analytic methods, including the Kaplan-Meier approach for estimating the survival distribution. Median time to progression and 95% confidence intervals will be estimated from the Kaplan-Meier curves.
Outcome Measure
Progression-free Survival (PFS)
Outcome Time Frame
From randomization until documented tumor recurrence or death from any cause, assessed up to 5 years
Secondary Ids
Secondary Id
NCI-2013-01224
Secondary Id
07-062
Secondary Id
NCI-2012-00458
Secondary Id
08-03-060
Secondary Id
P30CA013330
Secondary Outcomes
Outcome Description
Associations of PFS with tumor tissue expression levels of IGF-1 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Outcome Time Frame
Up to 5 years
Outcome Measure
Expression Levels of IGF-1
Outcome Description
Associations of PFS with tumor tissue expression levels of IGF-2 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Outcome Time Frame
Up to 5 years
Outcome Measure
Expression Levels of IGF-2
Outcome Description
Associations of PFS with tumor tissue expression levels of IGFBP-1 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Outcome Time Frame
Up to 5 years
Outcome Measure
Expression Levels of IGFBP-1
Outcome Description
Associations of PFS with tumor tissue expression levels of IGFBP-3 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Outcome Time Frame
Up to 5 years
Outcome Measure
Expression Levels of IGFBP-3
Outcome Description
Associations of PFS with tumor tissue expression levels of insulin receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Outcome Time Frame
Up to 5 years
Outcome Measure
Expression Levels of Insulin Receptor
Outcome Description
Associations of PFS with tumor tissue expression levels of IGF-1 receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Outcome Time Frame
Up to 5 years
Outcome Measure
Expression Levels of IGF-1 Receptor
Outcome Description
Associations of PFS with tumor tissue expression levels of estrogen receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Outcome Time Frame
Up to 5 years
Outcome Measure
Expression Levels of Estrogen Receptor
Outcome Description
Associations of PFS with tumor tissue expression levels of progesterone receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Outcome Time Frame
Up to 5 years
Outcome Measure
Expression Levels of Progesterone Receptor
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)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Dennis Yi-Shin Kuo
Investigator Email
DYKUO@montefiore.org
Investigator Phone
718-405-8086
MeSH Terms
PACLITAXEL
TAXES
CARBOPLATIN
BRACHYTHERAPY
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
DITERPENES
TERPENES
ECONOMICS
HEALTH CARE ECONOMICS AND ORGANIZATIONS
COORDINATION COMPLEXES
RADIOTHERAPY
THERAPEUTICS