Brief Summary
This is a multi-center, open-label Phase 0 Master Protocol designed to study the localized pharmacodynamics (PD) of anti-cancer therapies within the tumor microenvironment (TME) when administered intratumorally in microdose quantities via the CIVO device in patients with surface accessible solid tumors for which there is a scheduled surgical intervention. CIVO stands for Comparative In Vivo Oncology. Multiple substudies will include specified investigational agents and combinations to be evaluated.
Brief Title
Phase 0 Master Protocol for CIVO Intratumoral Microdosing of Anti-Cancer Therapies
Detailed Description
CIVO is a research tool composed of a hand-held single-use sterile injector coupled with fluorescent tracking microspheres called CIVO GLO that mark the sites of drug microdose injection, enabling rapid assessment of multiple oncology drugs or drug combinations simultaneously within a patient's tumor. Tumor responses to cancer treatments are highly context-specific and often involve complex interactions between the anti-cancer therapy, genetically diverse tumor cells, and a heterogeneous TME. This complexity is rarely modeled accurately in preclinical translational models of cancer. By utilizing intratumoral microdose injections with CIVO in advance of scheduled surgical intervention, this study will evaluate anti-cancer therapies directly in patients each with their own unique tumor genomic profile, intact TME, and immune system functional status. Because the platform delivers microdose amounts of each test agent or combination directly into the patient's tumor tissue, hypotheses can be tested earlier in the drug development process, consistent with the goals of the 2006 FDA Exploratory IND Guidance for Industry.
The CIVO device penetrates solid tumors and simultaneously delivers subtherapeutic microdoses of up to eight anti-cancer agents or combinations of anti-cancer agents co-injected with CIVO GLO into discrete regions of the tumor as drug columns. At the time of the planned surgical intervention (at least four hours to up to seven days after the CIVO microdose injection), the injected tumor tissue is then excised and tumor responses are assessed via histological staining of tumor cross-sections sampled perpendicular to each injection column. Co-injection with CIVO GLO enables identification of each injection site during resection as well as in tissues stained for analysis. This Phase 0 Master Protocol is aimed at distinguishing promising candidates earlier in the drug development process while also avoiding systemic toxicities associated with typical clinical exposures to these therapies.
The CIVO device penetrates solid tumors and simultaneously delivers subtherapeutic microdoses of up to eight anti-cancer agents or combinations of anti-cancer agents co-injected with CIVO GLO into discrete regions of the tumor as drug columns. At the time of the planned surgical intervention (at least four hours to up to seven days after the CIVO microdose injection), the injected tumor tissue is then excised and tumor responses are assessed via histological staining of tumor cross-sections sampled perpendicular to each injection column. Co-injection with CIVO GLO enables identification of each injection site during resection as well as in tissues stained for analysis. This Phase 0 Master Protocol is aimed at distinguishing promising candidates earlier in the drug development process while also avoiding systemic toxicities associated with typical clinical exposures to these therapies.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
800-530-5404
Central Contact Email
clinops@presagebio.com
Completion Date
Completion Date Type
Estimated
Conditions
Solid Tumor
Eligibility Criteria
\*This list is representative of study inclusion/exclusion criteria. Each substudy may include variations on these criteria.
Inclusion Criteria:
1. Ability and willingness to comply with the study's visit and assessment schedule.
2. Male or female ≥ 18 years of age at Visit 1 (Screening).
3. Pathologic diagnosis of \[solid tumors\] indicated in the relevant substudy(ies).
4. Ability and willingness to provide written informed consent. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
5. At least one lesion (primary tumor, recurrent tumor, or metastatic lymph node) that is surface accessible for CIVO injection that contains viable minimum tumor tissue volume and characteristics (e.g., based on clinical evaluation, available pre-operative imaging, pre-injection ultrasound imaging, or pathology reports indicating lesion with appropriate viable tumor volume without excessive cysts or necrosis) and for which there is a planned surgical intervention. The patient's presentation, surgical and pathology plan may determine whether a lesion is eligible with respect to a given CIVO MID needle configuration.
6. Female patients who:
* Are postmenopausal for at least one year before the screening visit, OR
* Are surgically sterile, OR
* Are of childbearing potential who agree to practice a highly effective method of contraception from the time of signing the Informed Consent Form (ICF) and during study participation OR agree to completely abstain from heterosexual intercourse.
* Agree to refrain from donating ova during study participation.
Male patients, even if surgically sterile (i.e., status post-vasectomy), who:
* Agree to practice effective barrier contraception from the time of signing the ICF and during study participation OR agree to completely abstain from heterosexual intercourse.
* Agree to refrain from donating sperm during study participation.
Exclusion Criteria:
1. Tumors near or involving critical structures for which, in the opinion of the treating clinician, injection would pose undue risk to the patient.
2. Female patients who are:
* Both lactating and breastfeeding, OR
* Have a positive β-subunit human chorionic gonadotropin (β-hCG) pregnancy test at screening verified by the Investigator.
3. Any uncontrolled intercurrent illness, condition, serious medical or psychiatric illness, or circumstance that, in the opinion of the Investigator, could interfere with adherence to the study's procedures or requirements, or otherwise compromise the study's objectives.
Inclusion Criteria:
1. Ability and willingness to comply with the study's visit and assessment schedule.
2. Male or female ≥ 18 years of age at Visit 1 (Screening).
3. Pathologic diagnosis of \[solid tumors\] indicated in the relevant substudy(ies).
4. Ability and willingness to provide written informed consent. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
5. At least one lesion (primary tumor, recurrent tumor, or metastatic lymph node) that is surface accessible for CIVO injection that contains viable minimum tumor tissue volume and characteristics (e.g., based on clinical evaluation, available pre-operative imaging, pre-injection ultrasound imaging, or pathology reports indicating lesion with appropriate viable tumor volume without excessive cysts or necrosis) and for which there is a planned surgical intervention. The patient's presentation, surgical and pathology plan may determine whether a lesion is eligible with respect to a given CIVO MID needle configuration.
6. Female patients who:
* Are postmenopausal for at least one year before the screening visit, OR
* Are surgically sterile, OR
* Are of childbearing potential who agree to practice a highly effective method of contraception from the time of signing the Informed Consent Form (ICF) and during study participation OR agree to completely abstain from heterosexual intercourse.
* Agree to refrain from donating ova during study participation.
Male patients, even if surgically sterile (i.e., status post-vasectomy), who:
* Agree to practice effective barrier contraception from the time of signing the ICF and during study participation OR agree to completely abstain from heterosexual intercourse.
* Agree to refrain from donating sperm during study participation.
Exclusion Criteria:
1. Tumors near or involving critical structures for which, in the opinion of the treating clinician, injection would pose undue risk to the patient.
2. Female patients who are:
* Both lactating and breastfeeding, OR
* Have a positive β-subunit human chorionic gonadotropin (β-hCG) pregnancy test at screening verified by the Investigator.
3. Any uncontrolled intercurrent illness, condition, serious medical or psychiatric illness, or circumstance that, in the opinion of the Investigator, could interfere with adherence to the study's procedures or requirements, or otherwise compromise the study's objectives.
Inclusion Criteria
inclusion/ Inclusion Criteria:
1. Ability and willingness to comply with the study's visit and assessment schedule.
2. Male or female ≥ 18 years of age at Visit 1 (Screening).
3. Pathologic diagnosis of \[solid tumors\] indicated in the relevant substudy(ies).
4. Ability and willingness to provide written informed consent. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
5. At least one lesion (primary tumor, recurrent tumor, or metastatic lymph node) that is surface accessible for CIVO injection that contains viable minimum tumor tissue volume and characteristics (e.g., based on clinical evaluation, available pre-operative imaging, pre-injection ultrasound imaging, or pathology reports indicating lesion with appropriate viable tumor volume without excessive cysts or necrosis) and for which there is a planned surgical intervention. The patient's presentation, surgical and pathology plan may determine whether a lesion is eligible with respect to a given CIVO MID needle configuration.
6. Female patients who:
* Are postmenopausal for at least one year before the screening visit, OR
* Are surgically sterile, OR
* Are of childbearing potential who agree to practice a highly effective method of contraception from the time of signing the Informed Consent Form (ICF) and during study participation OR agree to completely abstain from heterosexual intercourse.
* Agree to refrain from donating ova during study participation.
Male patients, even if surgically sterile (i.e., status post-vasectomy), who:
* Agree to practice effective barrier contraception from the time of signing the ICF and during study participation OR agree to completely abstain from heterosexual intercourse.
* Agree to refrain from donating sperm during study participation.
1. Ability and willingness to comply with the study's visit and assessment schedule.
2. Male or female ≥ 18 years of age at Visit 1 (Screening).
3. Pathologic diagnosis of \[solid tumors\] indicated in the relevant substudy(ies).
4. Ability and willingness to provide written informed consent. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
5. At least one lesion (primary tumor, recurrent tumor, or metastatic lymph node) that is surface accessible for CIVO injection that contains viable minimum tumor tissue volume and characteristics (e.g., based on clinical evaluation, available pre-operative imaging, pre-injection ultrasound imaging, or pathology reports indicating lesion with appropriate viable tumor volume without excessive cysts or necrosis) and for which there is a planned surgical intervention. The patient's presentation, surgical and pathology plan may determine whether a lesion is eligible with respect to a given CIVO MID needle configuration.
6. Female patients who:
* Are postmenopausal for at least one year before the screening visit, OR
* Are surgically sterile, OR
* Are of childbearing potential who agree to practice a highly effective method of contraception from the time of signing the Informed Consent Form (ICF) and during study participation OR agree to completely abstain from heterosexual intercourse.
* Agree to refrain from donating ova during study participation.
Male patients, even if surgically sterile (i.e., status post-vasectomy), who:
* Agree to practice effective barrier contraception from the time of signing the ICF and during study participation OR agree to completely abstain from heterosexual intercourse.
* Agree to refrain from donating sperm during study participation.
Gender
All
Gender Based
false
Keywords
HNSCC
SCCHN
lymphoma
sarcoma
breast adenocarcinoma
melanoma
intratumoral microdosing
microdose injection
microdosing
in vivo oncology
in vivo drug sensitivity
tumor microenvironment
multiplexed immunohistochemistry
head and neck cancer
pharmacodynamic biomarkers
CIVO
master protocol
precision oncology
soft tissue sarcoma
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04541108
Org Class
Industry
Org Full Name
Presage Biosciences
Org Study Id
PBI-MST-01
Overall Status
Recruiting
Phases
Early Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 0 Master Protocol Using the CIVO® Platform to Evaluate Intratumoral Microdoses of Anti-Cancer Therapies in Patients With Solid Tumors
Primary Outcomes
Outcome Description
Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumor microenvironment around each of the injection sites in each resected patient sample by IHC, ISH, or spatial biology platforms. An aggregate analysis of this quantification may be done across patient samples in each substudy to evaluate trends in tumor response. The biomarkers evaluated may include, but are not limited to biomarkers for cell death (e.g. cleaved caspase 3), T-cells (e.g. CD3, CD8/Granzyme B, CD4), natural killer (NK)/myeloid cells (e.g. CD56/Granzyme B, CD86, CD68, CD163), and proinflammatory cytokines (e.g., interferon gamma, tumor necrosis factor alpha, interferon gamma-induced protein 10).
Outcome Measure
Quantification of Selected Pharmacodynamic Biomarkers as Specified in Substudies by IHC, ISH, and/or Spatial Biology Platforms
Outcome Time Frame
4 hours-7 days after microdose injection
Secondary Ids
Secondary Id
MST01-TAK-02 (NCT06062602)
Secondary Id
MST01-MSD-03
Secondary Id
MST01-AZN-05 (NCT06366451)
Secondary Outcomes
Outcome Description
Relationship of AE to study drug(s) or CIVO device will be determined using an AE Relatedness Grading System.
Outcome Time Frame
Up to 28 days after microdose injection
Outcome Measure
Number of Patients with Adverse Events
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
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
Vikas Mehta
Investigator Email
vikameht@montefiore.org
Investigator Department
Otorhinolaryngology - Head & Neck Surgery
Investigator Sponsor Organization
External
Study Department
Otorhinolaryngology - Head & Neck Surgery
Study Division
Head and Neck Oncology
Categories Mesh Debug
Cancer --- SARCOMA
Sarcomas --- SARCOMA
Skin Cancer --- MELANOMA
Endocrine System Cancers --- HEAD AND NECK NEOPLASMS
Cancer --- CARCINOMA
Lung & Chest Cancers --- NEOPLASMS, GLANDULAR AND EPITHELIAL
Cancer --- NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- NEOPLASMS, CONNECTIVE AND SOFT TISSUE
Skin Cancer --- NEUROECTODERMAL TUMORS
Skin Cancer --- SKIN NEOPLASMS
MeSH Terms
SQUAMOUS CELL CARCINOMA OF HEAD AND NECK
LYMPHOMA
SARCOMA
MELANOMA
HEAD AND NECK NEOPLASMS
CARCINOMA, SQUAMOUS CELL
CARCINOMA
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
NEOPLASMS BY SITE
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
HEMIC AND LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
NEOPLASMS, CONNECTIVE AND SOFT TISSUE
NEUROENDOCRINE TUMORS
NEUROECTODERMAL TUMORS
NEOPLASMS, GERM CELL AND EMBRYONAL
NEOPLASMS, NERVE TISSUE
NEVI AND MELANOMAS
SKIN NEOPLASMS
SKIN DISEASES
SKIN AND CONNECTIVE TISSUE DISEASES
PEMBROLIZUMAB