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

NCT04931342 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: WO42178GOG-3051ENGOT-GYN2
• Study Type: interventional
• Target: 176
• Locations: 13 countries
• Sites: 41

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

Outcome Measures

Primary Outcomes (1)

• Confirmed Objective Response Rate (ORR)

  Confirmed ORR is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) (demonstrated on two consecutive occasions \>=4 weeks apart), as determined by the investigator according to RECIST v1.1.

  Up to approximately 5 years

Secondary Outcomes (10)

• Duration of Response (DOR)

  Up to approximately 5 years

• Disease Contral Rate (DCR)

  Up to approximately 5 years

• Progression Free Survival (PFS)

  Up to approximately 5 years

• 6-Month PFS Rate

  Up to 6 month

• Overall Survival (OS)

  Up to approximately 5 years

Study Arms (11)

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

EXPERIMENTAL

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

Drug: Ipatasertib; Drug: Paclitaxel

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

EXPERIMENTAL

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

Drug: Cobimetinib

Trastuzumab Emtansine (ERBB2-amplified/mutant tumors)

EXPERIMENTAL

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

Drug: Trastuzumab Emtansine

Atezolizumab + Bevacizumab (Non-matched)

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Bevacizumab

Giredestrant + Abemaciclib (ER+ tumors)

EXPERIMENTAL

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.

Drug: Giredestrant; Drug: Abemaciclib; Drug: Luteinizing Hormone-Releasing Hormone (LHRH) Agonists

Inavolisib + Palbociclib (PIK3CA-altered tumors)

EXPERIMENTAL

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

Drug: Inavolisib; Drug: Palbociclib

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

EXPERIMENTAL

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

Drug: Inavolisib; Drug: Palbociclib; Drug: Letrozole; Drug: Luteinizing Hormone-Releasing Hormone (LHRH) Agonists

Inavolisib + Olaparib (Non-matched)

EXPERIMENTAL

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

Drug: Inavolisib; Drug: Olaparib

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

EXPERIMENTAL

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

Drug: Giredestrant; Drug: Inavolisib

Inavolisib + Bevacizumab (PIK3CA-altered tumors)

EXPERIMENTAL

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

Drug: Bevacizumab; Drug: Inavolisib

Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched)

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Bevacizumab; Drug: Cyclophosphamide

Interventions

Ipatasertib DRUG

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

Also known as: RO5532961

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

Cobimetinib DRUG

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

Also known as: RO5514041

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

Trastuzumab Emtansine DRUG

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

Also known as: RO5304020

Trastuzumab Emtansine (ERBB2-amplified/mutant tumors)

Atezolizumab DRUG

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

Also known as: RO5541267, Tecentriq

Atezolizumab + Bevacizumab (Non-matched); Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched)

Bevacizumab DRUG

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

Also known as: RO4876646, Avastin

Atezolizumab + Bevacizumab (Non-matched); Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched); Inavolisib + Bevacizumab (PIK3CA-altered tumors)

Paclitaxel DRUG

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

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

Giredestrant DRUG

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

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

Abemaciclib DRUG

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

Giredestrant + Abemaciclib (ER+ tumors)

Inavolisib DRUG

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

Inavolisib + Giredestrant (ER+ and PIK3CA-altered tumors); Inavolisib + Olaparib (Non-matched); Inavolisib + Palbociclib (PIK3CA-altered tumors); Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors)

Palbociclib DRUG

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

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

Letrozole DRUG

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

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

Olaparib DRUG

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

Inavolisib + Olaparib (Non-matched)

Cyclophosphamide DRUG

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

Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched)

Luteinizing Hormone-Releasing Hormone (LHRH) Agonists 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.

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

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• GOG Foundation: collaborator
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator

Study Sites (41)

UCSF Helen Diller Family CCC

San Francisco, California, 94158, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63108, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Texas Oncology - Gulf Coast

The Woodlands, Texas, 77380, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

McGill University Health Centre - Glen Site

Montreal, Quebec, H4A 3J1, Canada

Location

Gynekologicko-porodnicka klinika

Prague, 120 00, Czechia

Location

CHU Besançon - Hôpital Jean Minjoz

Besançon, 25030, France

Location

Centre Francois Baclesse

Caen, 14076, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Groupe Hospitalier Diaconesses

Paris, 75020, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

ICO - Site René Gauducheau

Saint-Herblain, 44805, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Gustave Roussy

Villejuif, 94800, France

Location

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

Essen, 45136, Germany

Location

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

Location

A.O. U. Consorziale Policlinico di Bari

Bari, Apulia, 70124, Italy

Location

Istituto Tumori Napoli

Naples, Campania, 80131, Italy

Location

Policlinico Universitario Agostino Gemelli

Rome, Lazio, 00168, Italy

Location

IRCCS S. Raffaele

Milan, Lombardy, 20132, Italy

Location

LLC Medscan

Moskva, Moscow Oblast, 119421, Russia

Location

Samsung Medical Center

Seoul, (0)6351, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Institutio Catalan De Oncologia

Barcelona, 08908, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hôpitaux Universitaires de Genève

Geneva, 1205, Switzerland

Location

Adana Baskent University Medical Faculty; Oncology

Adana, 01220, Turkey (Türkiye)

Location

Baskent Universitesi Ankara Hastanesi; Tıbbi Onkoloji Bölümü

Ankara, 06490, Turkey (Türkiye)

Location

Koc University Medical Faculty; Department of Gynecology & Obstetrics

Istanbul, 34010, Turkey (Türkiye)

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

University College London Hospitals NHS Foundation Trust - University College Hospital

London, NW1 2PG, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

ipatasertib; cobimetinib; Ado-Trastuzumab Emtansine; atezolizumab; Bevacizumab; Paclitaxel; giredestrant; abemaciclib; inavolisib; palbociclib; Letrozole; olaparib; Gonadotropin-Releasing Hormone; Cyclophosphamide

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Oligopeptides; Nerve Tissue Proteins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 18, 2021
• Study Start: October 7, 2021
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): May 30, 2028
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CH (1); TU (3); GB (2); RU (1); KR (4); US (8); IT (4); AU (1); CA (2); FR (8); ES (4); DE (2); CZ (1)