A Study of MK-5684 in People With Certain Solid Tumors (MK-5684-015/OMAHA-015)

Official title

A Multicenter, Open-label, Phase 2 Basket Study of MK-5684 in Participants With Selected Solid Tumors (OMAHA-015)

Overview

Researchers want to learn if MK-5684 (the study medicine) can treat breast cancer, ovarian cancer, and endometrial cancer. MK-5684, the study medicine, is designed to treat cancer by blocking the body from making steroid hormones. Researchers will compare MK-5684 to the standard treatments for each cancer type in this study. The goal of this study is to learn if people who receive MK-5684 live longer without the cancer growing or spreading compared to people who receive a standard treatment.

Interventions

• Drug Opevesostat
  Tablet for oral administration.
• Drug Fludrocortisone/ Fludrocortisone acetate
  Tablet for oral administration.
• Drug Dexamethasone/Dexamethasone acetate
  Tablet for oral administration.
• Drug Rescue Medications
  Hydrocortisone or hydrocortisone/hydrocortisone acetate administered via intramuscular injection as rescue medication.
• Drug Fulvestrant
  Administered via intramuscular injection.
• Drug Exemestane
  Tablet for oral administration.
• Drug Megestrol acetate/Medroxyprogesterone acetate
  Tablet for oral administration.
• Drug Tamoxifen
  Tablet for oral administration.
• Drug Letrozole
  Tablet for oral administration.

Primary outcome measures

• Progression-Free Survival (PFS) - All Cohorts [Time frame: Up to approximately 2 years]

Secondary outcome measures (6)

• Overall Survival (OS) - All Cohorts [Time frame: Up to approximately 2 years]
• Clinical Benefit Rate (CBR) - Cohort A [Time frame: Up to approximately 2 years]
• Objective Response Rate (ORR) - All Cohorts [Time frame: Up to approximately 2 years]
• Duration of Response (DOR) - All Cohorts [Time frame: Up to approximately 2 years]
• Number of Participants who Discontinue Study Intervention Due to an Adverse Event (AE) - All Cohorts [Time frame: Up to approximately 8 months]
• Number of Participants who Experience One or More Adverse Events (AEs) - All Cohorts [Time frame: Up to approximately 11 months]

Eligibility criteria

Inclusion criteria

The main inclusion criteria include but are not limited to the following:

• Cohort A:

• Has a diagnosis of hormone receptor positive/Human Epidermal Growth Factor Receptor 2 negative (HR+/HER2-) invasive breast carcinoma that is either locally advanced disease not amenable to resection with curative intent (herein called unresectable) or metastatic disease not treatable with curative intent.
• Has experienced disease progression on or after at least 1 prior endocrine-based therapy in the metastatic setting and received either, 1 line of an approved protocol-specified combination endocrine-based therapy, or 2 or more lines of protocol-specified endocrine-based therapy in the metastatic setting
• Cohort B:

• Has histologically confirmed high-grade epithelial (including high-grade serous or predominantly serous, high-grade endometrioid, malignant mixed Müllerian tumors \[carcinosarcoma\], or clear cell) ovarian, fallopian tube, or primary peritoneal carcinoma.
• Has received between 4 to 8 cycles of platinum-based doublet chemotherapy in third-line (3L) setting for ovarian cancer.
• Cohort C:

• Histologically confirmed diagnosis of primary advanced or recurrent low-grade endometrioid carcinoma (eg, Federation of Gynecology and Obstetrics \[FIGO\] Grade 1/2, or well/moderately differentiated).
• Treatment naïve or has received up to 1 prior line of platinum-based therapy in either the advanced/metastatic OR adjuvant/neoadjuvant setting.
• All Cohorts :

• Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline.
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
• Participants who are Hepatitis B surface antigen positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load.
• Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.

Exclusion criteria

The main exclusion criteria include but are not limited to the following:

• Cohort A:

• Breast cancer amenable to treatment with curative intent.
• Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications, such as lymphangitic lung metastases, radiographic evidence of intratumoral cavitation or invasion/infiltration of a major blood vessel, bone marrow replacement, carcinomatous meningitis, significant symptomatic liver metastases, symptomatic pericardial effusion, symptomatic peritoneal carcinomatosis, or the need to achieve rapid symptom control.
• Cohort B:

• Has nonepithelial cancers (germ cell tumors and sex cord-stromal tumors), borderline tumors (low malignant potential), mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor, low-grade serous, low-grade endometrioid, and undifferentiated carcinoma.
• Has platinum-resistant ovarian cancer (defined as disease that has progressed per radiographic imaging within 180 days after the last dose of first-line \[1L\] platinum-based therapy) or platinum-refractory ovarian cancer (defined as disease that has progressed per radiographic imaging while receiving or within 28 days of the last dose of 1L platinum based therapy).
• Is a candidate for curative-intent surgery or curative-intent radiotherapy for ovarian cancer.
• Cohort C:

• Has high-grade (FIGO Grade 3 or poorly differentiated) endometrioid carcinoma and nonendometrioid histologies of any type (including serous, clear cell, mixed, carcinosarcoma), and neuroendocrine tumors are not eligible. Uterine mesenchymal tumors such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas, and adenosarcomas are not eligible.
• Is a candidate for curative-intent surgery or curative-intent radiotherapy.
• All Cohorts:

• Has confirmed or suspected adrenal metastases.
• Has known difficulty in tolerating oral medications, unable to swallow orally administered medication, or conditions which would impair absorption of oral medications.
• Has any prior history or current condition of adrenal insufficiency.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has known active central nervous system metastases and/or carcinomatous meningitis.
• Has a history of stem cell/solid organ transplant.
• Has not adequately recovered from major surgery or has ongoing surgical complications.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 10 centers

• Alaska Womens Cancer Care ( Site 0037) — Anchorage
• Mount Sinai Cancer Center ( Site 0009) — Miami Beach
• TRIALS 365 ( Site 0022) — Shreveport
• Mary Lanning Healthcare ( Site 0019) — Hastings
• John Theurer Cancer Center at Hackensack University Medical Center ( Site 0021) — Hackensack
• Rockefeller Outpatient Pavilion ( Site 0002) — New York
• The James Cancer Hospital and Solove Research Institute at The Ohio State University Compr — Columbus
• Baylor College of Medicine Medical Center ( Site 0004) — Houston
• … and 2 more centers

United Kingdom · 8 centers

• University Hospitals Sussex NHS Foundation Trust ( Site 2301) — East Sussex
• The Royal Cornwall Hospital ( Site 2306) — Truro
• St Bartholomew's Hospital ( Site 2302) — London
• University College Hospital London ( Site 2303) — London
• Guy's & St Thomas' NHS Foundation Trust ( Site 2309) — London
• Western General Hospital ( Site 2307) — Edinburgh
• Queen Elizabeth Hospital ( Site 2305) — Birmingham
• The Christie NHS Foundation Trust ( Site 2300) — Manchester

Brazil · 6 centers

• Hospital Santa Rita de Cassia ( Site 3104) — Vitória
• Obras Sociais Irma Dulce ( Site 3112) — Salvador
• Hospital Felicio Rocho ( Site 3105) — Belo Horizonte
• Hospital de Cancer de Pernambuco ( Site 3103) — Recife
• Liga Norte Riograndense Contra o Cancer ( Site 3108) — Natal
• Instituto Nacional de Câncer - INCA ( Site 3107) — Rio de Janeiro

Spain · 5 centers

• Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 2000) — L'Hospitalet de Llobregat
• CHUAC-Complejo Hospitalario Universitario A Coruña ( Site 2003) — A Coruña
• Clinica Universitaria Navarra - Madrid ( Site 2004) — Madrid
• Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 2002) — Madrid
• HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 2001) — Madrid

Turkey (Türkiye) · 5 centers

• Baskent Universitesi Adana Dr. Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 2201) — Adana
• Hacettepe Universitesi ( Site 2200) — Ankara
• Trakya Üniversitesi Eğitim Araştırma Hastanesi ( Site 2204) — Edirne
• Istanbul Universitesi Cerrahpasa ( Site 2203) — Istanbul
• Koc University, School of Medicine ( Site 2202) — Istanbul

Chile · 4 centers

• FALP ( Site 3300) — Santiago
• Pontificia Universidad Catolica de Chile ( Site 3307) — Santiago
• Bradfordhill ( Site 3301) — Santiago
• ONCOCENTRO APYS ( Site 3302) — Viña del Mar

Peru · 4 centers

• Instituto Regional de Enfermedades Neoplasicas del Centro (IREN CENTRO) ( Site 3405) — Concepción
• Clínica San Antonio ( Site 3404) — Trujillo
• IPOR Instituto Peruano de Oncología & Radioterapia ( Site 3400) — Lima
• Instituto Nacional de Enfermedades Neoplásicas ( Site 3401) — Lima

Argentina · 3 centers

• Hospital Aleman ( Site 0301) — Ciudad Autonoma de Buenos Aires
• Centro Medico Dr. Doreski - Fundación Respirar ( Site 0302) — Buenos Aires
• Instituto Alexander Fleming ( Site 0303) — Buenos Aires

Canada · 3 centers

• Princess Margaret Cancer Centre ( Site 0202) — Toronto
• Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0200) — Montreal
• Jewish General Hospital ( Site 0201) — Montreal

Malaysia · 3 centers

• Sarawak General Hospital ( Site 0602) — Kuching
• Pantai Hospital Kuala Lumpur ( Site 0603) — Kuala Lumpur
• University Malaya Medical Centre ( Site 0601) — Kuala Lumpur

Taiwan · 3 centers

• Taichung Veterans General Hospital ( Site 1004) — Taichung
• National Cheng Kung University Hospital ( Site 1003) — Tainan
• Mackay Memorial Hospital ( Site 1002) — Taipei

Thailand · 3 centers

• Chulalongkorn Hospital ( Site 1114) — Bangkok
• Faculty of Medicine Siriraj Hospital ( Site 1111) — Bangkok
• Songklanagarind Hospital ( Site 1113) — Songkhla

Singapore · 1 center

• National Cancer Centre Singapore ( Site 0800) — Singapore

Identifiers

NCT: NCT06979596 · 5684-015 · 2024-519563-18-00 · U1111-1315-5430 · MK-5684-015 · OMAHA-015

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗