Sacituzumab Govitecan for Relapsed Ovarian, Endometrial, and Cervical Carcinomas
- Conditions
- Recurrent Platinum Resistant Epithelial Ovarian CarcinomaRecurrent Epithelial Endometrial CarcinomaRecurrent Epithelial Cervical Carcinoma
- Interventions
- Registration Number
- NCT06865677
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Background:
Cancers of the female reproductive organs often come back after treatment. A drug called sacituzumab govitecan (SG) has been approved for use in other types of cancers. Researchers want to see if SG can also help people with ovarian, endometrial, or cervical cancers.
Objective:
To test SG in people with ovarian, endometrial, or cervical cancers.
Eligibility:
People aged 18 years and older with ovarian, endometrial, or cervical cancer. Their cancers must have returned after at least 2 rounds of standard treatments.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and a test of their heart function. They also will have biopsies to get new tissues samples taken from their tumors.
SG is infused through a tube attached to a needle inserted into a vein in the arm. Treatment will be given in 21-day cycles. Participants will receive SG on days 1 and 8 of each cycle. Each infusion takes 1 to 3 hours.
Participants may receive SG for up to 5 years. They can continue as long as the drug is helping them. Imaging scans and other tests will be repeated throughout the study period.
Participants will have an end-of-treatment visit within 2 weeks and a safety visit about 30 days after they stop treatment. Physical exams, blood tests, and imaging scans may be repeated.
Participants will then be contacted by phone every 6 months for up to 10 years after their first dose of SG.
Sponsoring Institution:
National Cancer Institute
- Detailed Description
Background:
* Human trophoblast cell-surface marker (TROP2) is a surface glycoprotein originally identified in human placental tissue and highly expressed in gynecologic malignancies. TROP2 overexpression in ovarian, endometrial, and cervical cancers is linked to tumorigenicity and poor overall survival.
* Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) of an IgG(kappa)1 monoclonal antibody targeting TROP2 with a chemotherapeutic payload of SN-38. SN-38 is an active metabolite of irinotecan and acts as a topoisomerase I inhibitor.
* Preclinical data suggest that SG induces DNA damage, replication stress, and tumor shrinkage in drug-resistant ovarian, endometrial, and cervical cancer in vitro and in vivo preclinical models.
* Further clinical and translational studies are needed to better understand SG s clinical activity and biology in relapsed gynecologic cancer patients.
Objective:
-To determine the objective response rate (ORR) of sacituzumab govitecan (SG) in participants with recurrent gynecological malignancies, calculated for each individual tumor histology by RECIST v1.1.
Eligibility:
* Age \>= 18 years
* ECOG performance status \<= 1
* Histologically documented, recurrent platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer (referred to as ovarian cancer); recurrent endometrioid or serous endometrial cancer; or recurrent epithelial cervical cancer
* At least two prior systemic therapeutic regimens
* Measurable disease by RECIST v1.1 criteria with lesions that can be safely biopsied
* No prior TROP2-targeting ADC
Design:
* This is an open label, non-randomized Phase II pilot study with one Arm.
* SG will be administered intravenously (IV) at 10 mg/kg on Days 1 and 8 each 21-day cycle.
* Tumor assessments will be time-based: every 9 weeks (+/- 1 week) for the first year and every 12 weeks (+/- 1 week) thereafter until disease progression. Pre-treatment biopsies and serial blood samples will be collected for the correlative studies.
* Treatment will be given for a maximum of 5 years or until disease progression or unacceptable toxicities.
* Up to 66 evaluable participants will be enrolled.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- Female
- Target Recruitment
- 95
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1 Sacituzumab govitecan Treatment with sacituzumab govitecan (SG)
- Primary Outcome Measures
Name Time Method Determine the ORR of SG in participants with recurrent gynecological malignancies, calculated for each individual tumor histology by RECIST v1.1 CT/MRI every 9 weeks (+/- 1 week) for the first year and then every 12 weeks (+/-1 week) until progressive disease or up to 5 years and at end of treatment which occurs within 14 days after the end of therapy. ORR (the fraction of PR or CR) will be calculated along with a 95% confidence interval for each cohort. The proportion of participants who achieve a response will be reported separately for each cohort, along with 95% confidence intervals (Clopper-Pearson).
- Secondary Outcome Measures
Name Time Method Determine the median DoR of SG Every 9 weeks for the first year and then every 12 weeks until progressive disease or up to 5 years and at end of treatment which occurs within 14 days after the end of therapy. DOR will be calculated by the Kaplan-Meier method, starting at date response was identified until progression or the response is declared to have ended, if the participants have a PR or CR. The median DOR will be reported along with a 95% confidence interval by cohort.
Determine the Overall Survival of participants receiving SG Days 1, 8, and 15 of each cycle for up to 5 years, at end of treatment (within 14 days after the end of therapy), 30-day safety visit and every 6 months during follow up OS will be calculated from on-study date until date of 10-year follow-up, using the Kaplan-Meier method by cohort. The ten-year OS rate, which is the percentage of people in a study or treatment group who are alive ten years after their initiation of the study treatment. The median OS will be reported along with a 95% confidence interval by cohort.
Determine the PFS of participants receiving SG Every 9 weeks for the first year and then every 12 weeks until PD or up to 5 years and at EOT which occurs within 14 days after the end of therapy. PFS will be calculated from on-study date until date of progression or death without progression, using the Kaplan-Meier method by cohort. The median PFS will be reported along with a 95% confidence interval by cohort.
Determine the safety of SG Days 1, 8, and 15 of each cycle, at end of treatment (within 14 days after), and 30 days after the end of treatment. Beyond 30 days after the last intervention only adverse events which are serious and related to the study intervention will be assessed. Safety will be reported by describing AE per CTCAE v5.0, by type and grade of toxicity.
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Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
National Institutes of Health Clinical Center🇺🇸Bethesda, Maryland, United States