Belzutifan in Recurrent Clear Cell Carcinoma of Gynecologic Origin
A Phase II Trial of Belzutifan in Patients With Recurrent or Persistent Clear Cell Carcinoma of the Ovary or Clear Cell Carcinoma of Other Gynecologic Origin
1 other identifier
interventional
32
1 country
2
Brief Summary
The purpose of this research study is to see if the study drug Belzutifan is effective and safe for participants with clear cell gynecologic malignancy, including but not limited to, ovarian cancer, endometrial cancer, cervical cancer, vaginal cancer, vulvar cancer, or endometriosis-related cancer. The name of the study drug involved in this study is: \- Belzutifan (a type of Hypoxia-Inducible Factor-2 alpha (HIF-2a) inhibitor)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2 ovarian-cancer
Started Dec 2024
Typical duration for phase_2 ovarian-cancer
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 5, 2024
CompletedFirst Posted
Study publicly available on registry
November 6, 2024
CompletedStudy Start
First participant enrolled
December 20, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2029
November 5, 2025
November 1, 2025
2 years
November 5, 2024
November 3, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Objective Response Rate (ORR)
ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete
ORR expected to be observed up to 3 years.
Progression Free Survival at 6 months (PFS6)
Progression-Free Survival at 6 Months (PFS6) is defined as the proportion of participants who are alive without disease progression for at least 6 months after initiating study treatment.
Disease will be evaluated at baseline and every 2 cycles on treatment, where each cycle is 4 weeks. Relevant to this endpoint is the 6 month timepoint.
Secondary Outcomes (4)
Grade 4 Treatment-Related Toxicity Rate
AEs expected to be observed up to 3 years.
Median Progression Free Survival (PFS)
Disease is evaluated at baseline, every 2 cycles on treatment (each cycle is 4 weeks), and in follow-up every 3 months (if off not due to PD), up to 3 years.
Median Overall Survival (OS)
Survival is evaluated in follow-up every 6 months (off due to PD) or every 3 months (off not due to PD), up to 3 years.
Clinical Benefit Rate (CBR)
Disease will be evaluated every 2 cycles on treatment (each cycle is 4 weeks); Treatment continues until disease progression or unacceptable toxicity. Treatment duration is expected to be up to 3 years.
Study Arms (1)
Belzutifan
EXPERIMENTAL15 participants will be enrolled for Stage 1 and will complete: * Baseline in-clinic visit * Imaging every 2 cycles * ECG on Day 1 of each cycle * Cycle 1 through End of Treatment: * Day 1 through 28 of 28 day cycle: Predetermined dose of Belzutifan 1x daily. * Day 15 of 28 day cycle: in-clinic visit * Cycle 2 Day 15 of 28 day cycle: in-clinic visit * End of treatment visit with ECG, blood tests, and imaging. * 30 Day post-treatment visit * Long-term follow up: every 6 months for 3 years * If 3 or more participants have objective response OR 2 or more participants are progression-free at 6 months, the study will enroll an additional 14 participants for Stage 2. Otherwise, enrollment will stop if there are less than 3 participants with objective response AND less than 2 participants are progression-free at 6 months.
Interventions
A Hypoxia-Inducible Factor-2 alpha inhibitor, 40 mg immediate-release tablet, taken orally per protocol.
Eligibility Criteria
You may qualify if:
- Participants must have histologically or cytologically confirmed recurrent or persistent clear cell carcinoma of the ovary (CCOC) or clear cell carcinoma of other gynecologic origin (e.g., endometrial, cervical, vaginal, vulvar, endometriosis-related). If mixed histology, then ≥50% clear cell component.
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Participants must have received at least one prior platinum-based chemotherapeutic regimen for primary management of disease.
- Prior bevacizumab is allowed.
- Prior use of immunotherapy is allowed.
- Unlimited prior lines for the treatment of recurrent or persistent disease are allowed.
- Age ≥18 years. Because no dosing or adverse event data are currently available on the use of Belzutifan in participants \<18 years of age, children are excluded from this study.
- ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1 (Karnofsky performance scale ≥70%, see Appendix A).
- Participants must meet the following organ and marrow function as defined below:
- Absolute neutrophil count ≥ 1,500/mcL
- Hemoglobin ≥ 10.0 g/dL (without use of erythropoietin; without packed red blood cell (RBC) transfusion within preceding 2 weeks)
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 ULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal (ULN) (in the absence of liver metastases) or ≤ 5 x institutional ULN (in the presence of liver metastases)
- Creatinine ≤ 1.5 x institutional upper limit of normal (ULN) OR estimated creatinine clearance (CrCl) by the Cockcroft-Gault formula
- +11 more criteria
You may not qualify if:
- Prior use of Belzutifan or another HIF-2a inhibitor.
- Participant has any of the following:
- Pulse oximeter reading \<92% at rest, or
- Requires intermittent supplemental oxygen, or
- Requires chronic supplemental oxygen
- Anti-cancer treatment (chemotherapy, radiotherapy, or other investigational therapy) within 4 weeks prior to entering the study (6 weeks prior to study entry for nitrosoureas or mitomycin C).
- Prior small molecule kinase inhibitor (including investigational kinase inhibitor) ≤ 2 weeks prior to entering the study.
- Prior radiation therapy within 2 weeks of start of study drugs. Participants must have recovered from all radiation-related toxicities and must not require steroids. Participants must not have had radiation pneumonitis. Palliative radiation (≤2 weeks of radiotherapy) to non-CNS (central nervous system) disease is permitted, provided there is at least a 1-week washout prior to start of study drugs.
- Use of herbal supplements, including but not limited to: cannabis, St. John's wort, gingko biloba, ginseng, saw palmetto, and ephedra. Herbal supplements must be stopped at least 1 week prior to beginning study treatment.
- Participants who are known to require concomitant therapy with moderate or strong CYP3A4 inducers. Due to potential drug interactions, concomitant use of these medications is not permitted for the duration of treatment on trial. Participants are eligible for study entry if an appropriate substitution is made prior the first dose of study medication.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Participants who have AEs due to previous anticancer therapies must have recovered to
- Grade 1 or baseline with the exception of alopecia. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have
- Grade 2 neuropathy are eligible.
- Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines are allowed.
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dana-Farber Cancer Institutelead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (2)
Brigham and Women's Hospital
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Panagiotis Konstantinopoulos, MD, PhD
Dana-Farber Cancer Institute
Central Study Contacts
Panagiotis Konstantinopoulos, MD, PhD
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
November 5, 2024
First Posted
November 6, 2024
Study Start
December 20, 2024
Primary Completion (Estimated)
December 30, 2026
Study Completion (Estimated)
June 30, 2029
Last Updated
November 5, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.