Belzutifan for Recurrent Gynecologic Clear Cell Carcinoma
This study is testing a drug called Belzutifan in people with recurrent (cancer that has come back) or persistent (cancer that has not gone away) clear cell carcinoma of gynecologic origin, such as ovarian, endometrial, or cervical cancer. Belzutifan is a targeted therapy that works by blocking a specific protein (Hypoxia-Inducible Factor-2 alpha) that cancer cells need to grow. The main goals are to see how many people respond to the treatment (Objective Response Rate) and how long people live without their cancer growing (Progression Free Survival at 6 months). You may be able to join if you are an adult woman with confirmed clear cell gynecologic cancer. The study is currently recruiting participants.
- Study design
- This is an open-label (you and your doctors will know you are receiving the study drug), non-randomized study involving up to 32 participants.
- What's involved
- You would have screening visits, regular in-clinic visits, electrocardiograms (ECGs), CT scans, MRI scans, and blood and urine tests.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your disease will be evaluated at baseline and every 2 cycles (each cycle is 4 weeks) on treatment, with responses expected to be observed for up to 3 years.
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NCT06677190
Belzutifan in Recurrent Clear Cell Carcinoma of Gynecologic Origin
Recruiting
PHASE2Ages 18+InterventionalTreatmentDana-Farber Cancer InstituteInvestigator-initiated
~32 participants
Updated 2025-11-05 on ClinicalTrials.gov
What's tested:Belzutifan
At a glance
Recruiting sites
2 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Objective Response Rate (ORR)
Measured over ORR expected to be observed up to 3 years.
+1 more outcome measured
Conditions
Where it's being run
2 sites across 1 statesMassachusetts2
Study leadership
- Panagiotis Konstantinopoulos, MD, PhD · PRINCIPAL_INVESTIGATOR · Dana-Farber Cancer Institute
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
INR OR PT and PTT ≤1.5 × institutional ULN unless participant is receiving anticoagulant therapy and PT/INR or PTT are within therapeutic range of that anticoagulation
Participants with known brain metastases are eligible if they have completed primary CNS-directed therapy (such as surgical resection or radiotherapy) and if they have remained clinically stable, asymptomatic, radiologically stable without evidence of progression for at least 4 weeks by repeat imaging and have been off of steroids for at least 4 weeks prior to starting study treatment.
Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the Belzutifan, as determined after discussion with the Sponsor-Investigator, are eligible for this trial.
Archival tumor tissue must be available as 17 (15 unstained + 2 H\&E) freshly serially cut slides from formalin-fixed, paraffin-embedded (FFPE) tissue blocks. The most recent available tissue is preferred to archived tissue. If fewer than 17 slides are available, the participant may still be eligible pending discussion with the Sponsor-Investigator.
The effects of Belzutifan on the developing human fetus are unknown. For this reason, women of child-bearing potential\* must have a negative serum or urine pregnancy test at the Screening and Cycle 1 Day 1 visits. A negative serum or urine pregnancy test must be obtained within 24 hours before the first dose of study intervention in order to start receiving the study drug. Women of child-bearing potential and men must agree to use adequate contraception (see Appendix D) prior to study entry, for the duration of study participation, and for at least 30 days after last receipt of study therapy. Additionally, should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
Female participants who do not meet the definition of women of child-bearing potential must meet either criteria:
Post-menopausal, defined as amenorrheic for at least 12 consecutive months within the appropriate age group and without an alternative medical cause OR
Surgically sterilized (i.e. bilateral oophorectomy, bilateral tubal ligation or salpingectomy, or total hysterectomy)
Ability to swallow orally administered medications.
Ability to understand and the willingness to sign a written informed consent document.
Exclusion
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.
Major surgical procedures within 4 weeks of beginning study treatment are not allowed. Minor surgical procedures (with the exception of port placement) within 1 week of beginning study treatment are not allowed.
Any gastrointestinal disorder that would interfere with the passage or absorption of oral medications. Participants must be able to swallow oral medications. Participants with an enteric tube (e.g., gastrostomy or jejunostomy tube), receiving total parenteral nutrition (TPN), or dependent on IV fluid support are ineligible.
Participants with significant cardiovascular impairment, including uncontrolled hypertension, congestive heart failure of New York Heart Association Grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia within the past 6 months.
Has moderate to severe hepatic impairment (Child-Pugh B or C).
Has received colony-stimulating factors (e.g., G-CSF, GM-CSF, or recombinant EPO)
Has a diagnosis of immunodeficiency.
Is known to be positive for Human Immunodeficiency Virus (HIV). Subjects with HIV, including those on antiretroviral therapy, are excluded due to risk of immunodeficiency and risk of overlapping toxicity.
Is known to be positive for Hepatitis B virus (HBV) or Hepatitis C virus (HCV). Participants are eligible if they have a history of HCV infection that has been treated and cured, with an undetectable viral load.
Participants with uncontrolled intercurrent illness, including but not limited to active infection and serious non-healing wounds or ulcers.
Participants with psychiatric illness/social situations that would limit compliance with study requirements.
Participants with a history of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biological composition to belzutifan.
Pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with belzutifan, breastfeeding participants are excluded from this study.
History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
What this trial measures
- Objective Response Rate (ORR)ORR expected to be observed up to 3 years.
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
- Progression Free Survival at 6 months (PFS6)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.
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.