A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors

NCT ID: NCT04931342

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-07
• Study Completion Date: 2028-05-30

Brief Summary

This study will evaluate the efficacy and safety of multiple biomarker-selected treatments in patients with persistent or recurrent rare epithelial ovarian, fallopian tube, or primary peritoneal tumors. Enrollment will take place in two phases: a preliminary phase followed by a potential expansion phase.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ipatasertib + Paclitaxel (PIK3CA/AKT1/PTEN-altered tumors)

Participants in the Ipatasertib + Paclitaxel arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group Type: EXPERIMENTAL

Ipatasertib

Intervention Type: DRUG

Ipatasertib will be administered by mouth once a day on Days 1-21 of each cycle. (Cycle length = 28 days)

Paclitaxel

Intervention Type: DRUG

Paclitaxel will be administered intravenously on Days 1, 8, and 15 of each cycle. (Cycle length=28 days)

Cobimetinib (BRAF/NRAS/KRAS/NF1-altered tumors)

Participants in the Cobimetinib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Cobimetinib will be administered by mouth once a day on Days 1-21 of each cycle. (Cycle length=28 days)

Trastuzumab Emtansine (ERBB2-amplified/mutant tumors)

Participants in the Trastuzumab Emtansine arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group Type: EXPERIMENTAL

Trastuzumab Emtansine

Intervention Type: DRUG

Trastuzumab Emtansine will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)

Atezolizumab + Bevacizumab (Non-matched)

Participants in the Atezolizumab + Bevacizumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)

Giredestrant + Abemaciclib (ER+ tumors)

Participants in the Giredestrant + Abemaciclib arm will receive treatment until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Group Type: EXPERIMENTAL

Giredestrant

Intervention Type: DRUG

Giredestrant will be administered by mouth once a day on Days 1-28 of each cycle (Cycle length=28 days)

Abemaciclib

Intervention Type: DRUG

Abemaciclib will be administered by mouth twice a day during each 28-day cycle

Luteinizing Hormone-Releasing Hormone (LHRH) Agonists

Intervention Type: DRUG

LHRH agonists are required beginning at least 2 weeks prior to initiation of study treatment for premenopausal or perimenopausal women. Acceptable agents include goserelin or leuprolide; triptorelin is also acceptable. Monthly injections of LHRH agonist are preferred.

Inavolisib + Palbociclib (PIK3CA-altered tumors)

Participants in the Inavolisib + Palbociclib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group Type: EXPERIMENTAL

Inavolisib

Intervention Type: DRUG

Inavolisib will be administered by mouth once a day on Days 1-28 of each 28-day cycle

Palbociclib

Intervention Type: DRUG

Palbociclib will be administered by mouth once a day on Days 1-21 of each 28-day cycle

Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors)

Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group Type: EXPERIMENTAL

Inavolisib

Intervention Type: DRUG

Inavolisib will be administered by mouth once a day on Days 1-28 of each 28-day cycle

Palbociclib

Intervention Type: DRUG

Palbociclib will be administered by mouth once a day on Days 1-21 of each 28-day cycle

Letrozole

Intervention Type: DRUG

Letrozole will be administered by mouth once a day on Days 1-28 of each 28-day cycle

Luteinizing Hormone-Releasing Hormone (LHRH) Agonists

Intervention Type: DRUG

LHRH agonists are required beginning at least 2 weeks prior to initiation of study treatment for premenopausal or perimenopausal women. Acceptable agents include goserelin or leuprolide; triptorelin is also acceptable. Monthly injections of LHRH agonist are preferred.

Inavolisib + Olaparib (Non-matched)

Participants in the Inavolisib + Olaparib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group Type: EXPERIMENTAL

Inavolisib

Intervention Type: DRUG

Inavolisib will be administered by mouth once a day on Days 1-28 of each 28-day cycle

Olaparib

Intervention Type: DRUG

Olaparib will be administered by mouth twice a day on Days 1-28 of each 28-day cycle

Inavolisib + Giredestrant (ER+ and PIK3CA-altered tumors)

Participants in the Inavolisib + Giredestrant arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group Type: EXPERIMENTAL

Giredestrant

Intervention Type: DRUG

Giredestrant will be administered by mouth once a day on Days 1-28 of each cycle (Cycle length=28 days)

Inavolisib

Intervention Type: DRUG

Inavolisib will be administered by mouth once a day on Days 1-28 of each 28-day cycle

Inavolisib + Bevacizumab (PIK3CA-altered tumors)

Participants in the Inavolisib + Bevacizumab arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)

Inavolisib

Intervention Type: DRUG

Inavolisib will be administered by mouth once a day on Days 1-21 of each 21-day cycle

Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched)

Participants in the Atezolizumab + Bevacizumab + Cyclophosphamide arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide will be administered by mouth once a day on Days 1-21 of each cycle. (Cycle length = 21 days)

Interventions

Ipatasertib

Ipatasertib will be administered by mouth once a day on Days 1-21 of each cycle. (Cycle length = 28 days)

Intervention Type: DRUG

Cobimetinib

Cobimetinib will be administered by mouth once a day on Days 1-21 of each cycle. (Cycle length=28 days)

Intervention Type: DRUG

Trastuzumab Emtansine

Trastuzumab Emtansine will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)

Intervention Type: DRUG

Atezolizumab

Atezolizumab will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)

Intervention Type: DRUG

Bevacizumab

Bevacizumab will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)

Intervention Type: DRUG

Paclitaxel

Paclitaxel will be administered intravenously on Days 1, 8, and 15 of each cycle. (Cycle length=28 days)

Intervention Type: DRUG

Giredestrant

Giredestrant will be administered by mouth once a day on Days 1-28 of each cycle (Cycle length=28 days)

Intervention Type: DRUG

Abemaciclib

Abemaciclib will be administered by mouth twice a day during each 28-day cycle

Intervention Type: DRUG

Inavolisib

Inavolisib will be administered by mouth once a day on Days 1-28 of each 28-day cycle

Intervention Type: DRUG

Palbociclib

Palbociclib will be administered by mouth once a day on Days 1-21 of each 28-day cycle

Intervention Type: DRUG

Letrozole

Letrozole will be administered by mouth once a day on Days 1-28 of each 28-day cycle

Intervention Type: DRUG

Olaparib

Olaparib will be administered by mouth twice a day on Days 1-28 of each 28-day cycle

Intervention Type: DRUG

Luteinizing Hormone-Releasing Hormone (LHRH) Agonists

LHRH agonists are required beginning at least 2 weeks prior to initiation of study treatment for premenopausal or perimenopausal women. Acceptable agents include goserelin or leuprolide; triptorelin is also acceptable. Monthly injections of LHRH agonist are preferred.

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide will be administered by mouth once a day on Days 1-21 of each cycle. (Cycle length = 21 days)

Intervention Type: DRUG

Inavolisib

Inavolisib will be administered by mouth once a day on Days 1-21 of each 21-day cycle

Intervention Type: DRUG

Other Intervention Names

RO5532961; RO5514041; RO5304020; RO5541267, Tecentriq; RO4876646, Avastin

Eligibility Criteria

Inclusion Criteria

• Persistent or recurrent EOC that meets the following criteria: Histologically confirmed non-high-grade serous, non-high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer, including but not limited to low-grade serous ovarian carcinoma, clear cell carcinoma, mucinous carcinoma, carcinosarcoma, undifferentiated carcinoma, seromucinous carcinoma, malignant Brenner tumors, Grades 1 or 2 endometrioid carcinoma, mesonephric-like adenocarcinoma and small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Disease that is not amenable to curative surgery
• Measurable disease (at least one target lesion) according to RECIST v1.1
• Previous treatment with one to four lines of therapy, at least one of which was platinum-based. Hormonal therapy does not count as a line of therapy.
• Platinum-resistant disease, defined as disease progression during or within 6 months of last platinum therapy, with the following exception: Participants with primary platinum-refractory disease are excluded.
• Submission of a representative tumor specimen that is suitable for next-generation sequencing (NGS) testing and estrogen receptor immunohistochemistry (ER IHC) to determine treatment arm assignment and for central pathology review.
• Submission of the local pathology report and, if available, any associated stained slides that supported the local diagnosis of the histology (to be used for central pathology review)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs (if applicable)

Exclusion Criteria

• Pregnant or breastfeeding, or intending to become pregnant or breastfeed during the study
• Primary platinum-refractory disease, defined as progression during or within 4 weeks after the last dose of the first-line platinum treatment
• Histologic diagnosis of high-grade serous or high-grade endometrioid ovarian, fallopian tube, or primary peritoneal cancer
• Current diagnosis of solely borderline epithelial ovarian tumor
• Current diagnosis of non-epithelial ovarian tumors
• Current diagnosis of synchronous primary endometrial cancer
• Prior history of primary endometrial cancer, with the following exception: a prior diagnosis of primary endometrial cancer is permitted if it meets all of the following conditions: Stage IA, no lymphovascular invasion, International Federation of Gynecology and Obstetrics Grade 1 or 2, not a high-grade subtype.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Symptomatic, untreated, or actively progressing CNS metastases
• Severe infection within 4 weeks prior to initiation of study treatment
• Treatment with chemotherapy, radiotherapy, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, or investigational therapy within 28 days prior to initiation of study treatment
• Treatment with hormonal therapy within 14 days prior to initiation of study treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GOG Foundation

NETWORK

Sponsor Role: collaborator

European Network of Gynaecological Oncological Trial Groups (ENGOT)

OTHER

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

UCSF Helen Diller Family CCC

San Francisco, California, United States

Washington University School of Medicine

St Louis, Missouri, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Texas Oncology - Gulf Coast

The Woodlands, Texas, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, United States

Cabrini Hospital

Malvern, Victoria, Australia

Princess Margaret Cancer Center

Toronto, Ontario, Canada

McGill University Health Centre - Glen Site

Montreal, Quebec, Canada

Gynekologicko-porodnicka klinika

Prague, , Czechia

CHU Besançon - Hôpital Jean Minjoz

Besançon, , France

Centre Francois Baclesse

Caen, , France

Centre Leon Berard

Lyon, , France

Groupe Hospitalier Diaconesses

Paris, , France

Centre Eugène Marquis

Rennes, , France

ICO - Site René Gauducheau

Saint-Herblain, , France

Institut Claudius Regaud

Toulouse, , France

Gustave Roussy

Villejuif, , France

Kliniken Essen-Mitte Evang. Huyssens-Stiftung, Klinik für Gynäkologie und gynäkologische Onkologie

Essen, , Germany

Universitätsklinikum Mannheim

Mannheim, , Germany

A.O. U. Consorziale Policlinico di Bari

Bari, Apulia, Italy

Istituto Tumori Napoli

Napoli, Campania, Italy

Policlinico Universitario Agostino Gemelli

Rome, Lazio, Italy

IRCCS S. Raffaele

Milan, Lombardy, Italy

LLC Medscan

Moskva, Moscow Oblast, Russia

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Institutio Catalan De Oncologia

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Clinico Universitario Virgen de la Victoria

Málaga, , Spain

Hôpitaux Universitaires de Genève

Geneva, , Switzerland

Adana Baskent University Medical Faculty; Oncology

Adana, , Turkey (Türkiye)

Baskent Universitesi Ankara Hastanesi; Tıbbi Onkoloji Bölümü

Ankara, , Turkey (Türkiye)

Koc University Medical Faculty; Department of Gynecology & Obstetrics

Istanbul, , Turkey (Türkiye)

Western General Hospital

Edinburgh, , United Kingdom

University College London Hospitals NHS Foundation Trust - University College Hospital

London, , United Kingdom

Countries

United States; Australia; Canada; Czechia; France; Germany; Italy; Russia; South Korea; Spain; Switzerland; Turkey (Türkiye); United Kingdom

Other Identifiers

GOG-3051

Identifier Type: OTHER

Identifier Source: secondary_id

ENGOT-GYN2

Identifier Type: OTHER

Identifier Source: secondary_id

WO42178

Identifier Type: -

Identifier Source: org_study_id