A Phase 2 Study of belzutifan (MK-6482) Monotherapy in Participants with Advanced Pheochromocytoma/Paraganglioma (PPGL) or Pancreatic Neuroendocrine Tumor (pNET)
- Conditions
- Pheochromocytoma/Paraganglioma or Pancreatic Neuroendocrine TumorMedDRA version: 20.1Level: LLTClassification code 10034876Term: PheochromocytomaSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10073860Term: ParagangliomaSystem Organ Class: 100000004864MedDRA version: 21.0Level: LLTClassification code 10067518Term: Pancreatic neuroendocrine tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-005028-13-SE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 140
Cohort A1: Pheochromocytoma/Paraganglioma (PPGL)
1. Has documented histopathological diagnosis (local report) of pheochromocytoma or paraganglioma
2. Has locally advanced or metastatic disease that is not amenable to surgery or curative intent treatment
3. Adequately controlled blood pressure defined as blood pressure =150/90 mm Hg (=135/85 mm Hg for adolescents) and with no change in antihypertensive medications (for participants with concomitant hypertension) for at least 2 weeks prior to start of study treatment
Cohort A2: Pancreatic Neuroendocrine Tumor (pNET)
4. Has documented histopathological or cytopathological diagnosis (local report) of well-differentiated, low or intermediate grade (G1 or G2 pNET per 2017 WHO classification and grading) pNET
5. Has locally advanced disease or metastatic disease that is:
a. Not amenable for surgery, radiation, locoregional therapies or combination modality of such treatments with curative intent
b. Experienced disease progression on or after at least 1 line of prior systemic therapy that includes an approved targeted agent such as everolimus (mTOR inhibitor) or sunitinib (antiVEGF targeted agent). Participants who have received >3 prior systemic therapies will be capped to =20% of the cohort
Cohorts A1 and A2
6. Has disease progression within the past 12 months from screening
7. Has measurable disease per RECIST v1.1 by CT or MRI as assessed by local site investigator/radiology assessment and verified in real time by BICR. BICR must confirm the presence of radiologically measurable disease per RECIST 1.1 for the participant to be eligible for the study
a. Irradiated lesions or lesions treated with locoregional therapies should not be used as target lesions unless they clearly demonstrate growth since completion of radiation
b. Metastatic lesions situated in the brain are not considered measurable and should be considered nontarget lesions
c. Only lesions of the primary indication for the cohort may be evaluated for measurability; other neoplastic lesions will be documented by the investigator and this information provided to the independent reviewers to ensure that such lesions are not included in the RECIST assessment
8. Is male or female, 12 years of age inclusive (=40 kg for adolescents [12-17 years of age]), at the time of signing the informed consent
9. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of study intervention:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent
OR
• Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
- Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant
• Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
10. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their prefe
1. Is unable to swallow orally administered medication or has a disorder that might affect the absorption of belzutifan
2. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years with the following exceptions:
a) Participants with history of VHL disease will be permitted provided concurrent lesions (other than PPGL for Cohort A1 and pNET for Cohort A2) are localized without immediate need for intervention
b) Prior history of surgical resection(s) for concurrent localized VHL disease-associated tumors is allowed provided there is no history of metastatic disease from concurrent tumors; history of systemic therapy for concurrent tumors will be exclusionary
c) Participants with history of other genetic syndromes will be allowed provided concurrent tumors (outside of the organ affected in Cohort A1 and Cohort A2, respectively) are localized and do not require immediate intervention; history of metastatic disease in concurrent tumors or history of systemic therapy for concurrent tumors will be exclusionary
3. Has known CNS metastases and/or carcinomatous meningitis
4. Has any of the following:
• Hypoxia as defined by a pulse oximeter reading <92% at rest, or
• Requires intermittent supplemental oxygen, or
• Requires chronic supplemental oxygen
5. Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction, or arterial bypass (CABG) or PTCA =6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Concurrent uncontrolled hypertension defined as blood pressure >150/90 mm Hg despite optimal antihypertensive medications within 2 weeks prior to the first dose of study treatment
6. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
7. Has had major surgery =4 weeks prior to first dose of study intervention
8. Has received prior treatment (except somatostatin analogs) with chemotherapy, targeted therapy, or other investigational therapy within the past 4 weeks of study entry, or prior biologics or immunotherapy within the past 6 weeks of study entry
9. Has received prior locoregional therapies or radiation within the past 4 weeks of study entry
10. Has received prior treatment with PRRT/radionuclide therapy or other radiopharmaceutical therapy within the past 12 weeks from screening for participants with pNET
11. Has received meta-iodobenzylguanidine (MIBG) therapy or other radiopharmaceutical therapy within the past 12 weeks from screening for participants with PPGL
12. Has received prior treatment with any HIF-2a inhibitor (including belzutifan)
13. Has a known hypersensitivity to the study treatment and/or any of its excipients
14. Has toxicities from prior locoregional or systemic or any other therapies that is not recovered to baseline or CTCAE =Grade 1 (with the exception of alopecia)
15. Has received colony-stimulating factors =28 days prior to the first dose of study intervention
16. Is currently receiving strong inhibitors of CYP3A4 that cannot be discontinued for the duration of the study
17. Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate (eg, bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study
18. Is cu
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method