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A Phase 1b/2 Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Raludotatug Deruxtecan With or Without Other Anticancer Investigational Agents in Participants With High-grade Serous Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Have Relapsed After Prior Platinum-based Chemotherapy

Status: Recruiting
Location: See all (23) locations...
Intervention Type: Drug, Biological
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

Researchers are looking for other ways to treat relapsed high-grade serous ovarian cancer. Relapsed means the cancer came back after treatment. High-grade means the cancer cells grow and spread quickly. Serous means the cancer started in the cells that cover the ovaries, the lining of the belly, or in the fallopian tubes. Standard treatment (usual treatment) for people with relapsed high-grade serous ovarian cancer may include: * Chemotherapy, which is a treatment that uses medicine to destroy cancer cells or stop them from growing * Targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread Raludotatug deruxtecan (R-DXd) is a study treatment that is an antibody drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. Researchers want to know if R-DXd is safe to take with other treatments and if people tolerate them together. They also want to learn how many people have the cancer respond (gets smaller or goes away) to the treatments.

Eligibility
Participation Requirements
Sex: Female
Minimum Age: 18
Healthy Volunteers: f
View:

• Has pathologically documented diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer

• Has measurable disease per Response Evaluation Criteria In Solid Tumors 1.1

• Participants in Cohort A-1 Arms 2 and 3: Has relapsed disease after 1 to 3 prior lines of therapy and radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease)

• Participants in Cohort B-1 and Cohort B-2: Has relapsed disease after 1 to 3 prior lines of therapy and radiographic evidence of disease progression \<6 months (\<180 days) after the last dose of platinum-based therapy (ie, platinum-resistant disease). Participants must have received no more than 1 prior bevacizumab-containing systemic treatment regimen

• Participants in Cohort B-1 and Cohort B-2: Is a candidate for bevacizumab treatment

• Has provided tumor tissue from a core or excisional biopsy of a tumor lesion not previously irradiated

• Has an Eastern Cooperative Oncology Group performance status of 0 to 1 assessed within 7 days before allocation/randomization

• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral 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 prior to allocation/randomization

• Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening

• Participants in Cohort C-1 and Cohort D: Has relapsed disease after 1 prior line of therapy, radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease) and progressed during prior treatment with PARPi in the first-line setting

• Cohort A-2 Arms 1, 2, and 3: Has relapsed disease after 1 prior line of therapy and radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease)

Locations
United States
Connecticut
Yale-New Haven Hospital-Smilow Cancer Hospital at Yale-New Haven ( Site 0019)
RECRUITING
New Haven
Kentucky
The University of Louisville, James Graham Brown Cancer Center ( Site 0009)
RECRUITING
Louisville
Massachusetts
Dana-Farber Cancer Institute ( Site 0015)
RECRUITING
Boston
New York
Memorial Sloan Kettering Cancer Center ( Site 0003)
RECRUITING
New York
Oklahoma
OU Health University of Oklahoma Medical Center ( Site 7000)
RECRUITING
Oklahoma City
Texas
Houston Methodist Hospital ( Site 0010)
RECRUITING
Houston
Utah
START Mountain Region ( Site 0008)
RECRUITING
West Valley City
Virginia
University of Virginia Health System ( Site 0011)
RECRUITING
Charlottesville
Other Locations
Israel
Rambam Health Care Campus ( Site 0202)
RECRUITING
Haifa
Shaare Zedek Medical Center ( Site 0201)
RECRUITING
Jerusalem
Sheba Medical Center ( Site 0200)
RECRUITING
Ramat Gan
Spain
Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0300)
RECRUITING
Barcelona
Institut Català d'Oncologia - L'Hospitalet ( Site 0302)
RECRUITING
L'hospitalet De Llobregat
Clinica Universidad de Navarra ( Site 0301)
RECRUITING
Madrid
Hospital Universitario 12 de Octubre ( Site 0304)
RECRUITING
Madrid
Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0303)
RECRUITING
Madrid
HOSPITAL UNIVERSITARIO PUERTA DE HIERRO MAJADAHONDA ( Site 0307)
RECRUITING
Majadhonda
Hospital Universitario Virgen de la Victoria ( Site 0306)
RECRUITING
Málaga
Hospital General Universitario de Valencia ( Site 0305)
RECRUITING
Valencia
United Kingdom
Royal Marsden Hospital ( Site 0402)
RECRUITING
Fulham
Barts Health NHS Trust ( Site 0401)
RECRUITING
London
The Christie NHS Foundation Trust ( Site 0405)
RECRUITING
Manchester
The Royal Marsden NHS Foundation Trust. ( Site 0403)
RECRUITING
Sutton
Contact Information
Primary
Toll Free Number
Trialsites@msd.com
1-888-577-8839
Time Frame
Start Date: 2025-04-15
Estimated Completion Date: 2029-03-27
Participants
Target number of participants: 460
Treatments
Experimental: Cohort A-1 Arm 1 (R-DXd + Carboplatin Dose 1)
Participants receive escalating doses of intravenous (IV) raludotatug deruxtecan (R-DXd) in combination with carboplatin at Dose 1. Participants can receive up to a maximum of six 3-week cycles of carboplatin (approximately 4 months) and will receive raludotatug deruxtecan until disease progression or discontinuation.
Experimental: Cohort A-1 Arm 2 (R-DXd + Paclitaxel)
Participants receive escalating doses of IV R-DXd in combination with paclitaxel. Participants can receive up to a maximum of six 3-week cycles of paclitaxel (approximately 4 months) and will receive R-DXd until disease progression or discontinuation.
Experimental: Cohort A-1 Arm 3 (R-DXd + Carboplatin Dose 2)
Participants receive escalating doses of intravenous (IV) R-DXd in combination with carboplatin at Dose 2. Participants can receive up to a maximum of six 3-week cycles of carboplatin (approximately 4 months) and will receive R-DXd until disease progression or discontinuation.
Experimental: Cohort B-1 (R-DXd + Bevacizumab)
Participants receive escalating doses of IV R-DXd in combination with bevacizumab until disease progression or discontinuation.
Experimental: Cohort B-2 (R-DXd RP2D + Bevacizumab)
Participants with platinum-resistant recurrent ovarian cancer (PRROC) receive recommended Phase 2 dose (RP2D) of IV R-DXd in combination with bevacizumab until disease progression or discontinuation.
Experimental: Cohort C-1 (R-DXd + Pembrolizumab)
Participants receive escalating doses of IV R-DXd in combination with pembrolizumab. Participants can receive up to a maximum of thirty-five 3-week cycles of pembrolizumab (approximately 2 years) and will receive R-DXd until disease progression or discontinuation.
Experimental: Cohort D (R-DXd RP2D +/- Bevacizumab)
Participants with platinum-sensitive recurrent ovarian cancer (PSROC) receive RP2D of IV R-DXd in combination with or without bevacizumab until disease progression or discontinuation.
Experimental: Cohort A-2 Arm 1 (R-DXd RP2D + Carboplatin +/- Bevacizumab)
Participants with PSROC will receive the RP2D of R-DXd in combination with a maximum of 6 cycles of carboplatin with or without bevacizumab, until disease progression or discontinuation.
Experimental: Cohort A-2 Arm 2 (R-DXd RP2D + Paclitaxel +/- Bevacizumab)
Participants with PSROC will receive the RP2D of R-DXd in combination with a maximum of 6 cycles of paclitaxel with or without bevacizumab, until disease progression or discontinuation.
Active_comparator: Cohort A-2 Arm 3 (Platinum-Based Doublet Chemotherapy +/- Bevacizumab)
Participants with PSROC will receive one of 3 regimens of investigator's choice of platinum-based doublet chemotherapy with or without bevacizumab. Platinum-based doublet chemotherapy will be administered for maximum of 8 cycles. Bevacizumab can be administered until disease progression or discontinuation.
Related Therapeutic Areas
Sponsors
Collaborators: Daiichi Sankyo
Leads: Merck Sharp & Dohme LLC

This content was sourced from clinicaltrials.gov

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