A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors
- Conditions
- Ovarian Cancer
- Interventions
- Drug: Luteinizing Hormone-Releasing Hormone (LHRH) Agonists
- Registration Number
- NCT04931342
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 176
- 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)
- In addition to the general inclusion criteria above, participants must meet all of the arm-specific inclusion criteria for the respective arm
General
- 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
- In addition to the general exclusion criteria above, participants can not meet any of the arm-specific exclusion criteria for the respective arm
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Giredestrant + Abemaciclib (ER+ tumors) Luteinizing Hormone-Releasing Hormone (LHRH) Agonists 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. Giredestrant + Abemaciclib (ER+ tumors) Giredestrant 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. Inavolisib + Palbociclib (PIK3CA-altered tumors) Inavolisib Participants in the Inavolisib + Palbociclib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors) Luteinizing Hormone-Releasing Hormone (LHRH) Agonists Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors) Inavolisib Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Inavolisib + Giredestrant (ER+ and PIK3CA-altered tumors) Giredestrant Participants in the Inavolisib + Giredestrant arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Trastuzumab Emtansine (ERBB2-amplified/mutant tumors) Trastuzumab Emtansine Participants in the Trastuzumab Emtansine arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Ipatasertib + Paclitaxel (PIK3CA/AKT1/PTEN-altered tumors) Paclitaxel Participants in the Ipatasertib + Paclitaxel arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Cobimetinib (BRAF/NRAS/KRAS/NF1-altered tumors) Cobimetinib Participants in the Cobimetinib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Atezolizumab + Bevacizumab (Non-matched) Atezolizumab 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. Atezolizumab + Bevacizumab (Non-matched) Bevacizumab 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. Giredestrant + Abemaciclib (ER+ tumors) Abemaciclib 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. Inavolisib + Palbociclib (PIK3CA-altered tumors) Palbociclib Participants in the Inavolisib + Palbociclib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors) Palbociclib Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors) Letrozole Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Inavolisib + Olaparib (Non-matched) Olaparib Participants in the Inavolisib + Olaparib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Inavolisib + Bevacizumab (PIK3CA-altered tumors) Bevacizumab Participants in the Inavolisib + Bevacizumab arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched) Cyclophosphamide 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. Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched) Atezolizumab 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. Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched) Bevacizumab 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. Inavolisib + Giredestrant (ER+ and PIK3CA-altered tumors) Inavolisib Participants in the Inavolisib + Giredestrant arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Inavolisib + Olaparib (Non-matched) Inavolisib Participants in the Inavolisib + Olaparib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Inavolisib + Bevacizumab (PIK3CA-altered tumors) Inavolisib Participants in the Inavolisib + Bevacizumab arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. Ipatasertib + Paclitaxel (PIK3CA/AKT1/PTEN-altered tumors) Ipatasertib Participants in the Ipatasertib + Paclitaxel arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
- Primary Outcome Measures
Name Time Method Confirmed Objective Response Rate (ORR) Up to approximately 5 years 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.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Up to approximately 5 years OS after start of treatment is defined as the time from start of treatment to death from any cause.
Confirmed ORR as Determined by IRC (Independent Review Committee) Up to approximately 5 years Confirmed ORR, as determined by the IRC according to RECIST v1.1.
Duration of Response (DOR) Up to approximately 5 years DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
Disease Contral Rate (DCR) Up to approximately 5 years DCR is defined as the proportion of participants with a confirmed CR or PR, or stable disease maintained for at least 16 weeks, as determined by the investigator according to RECIST v1.1.
DCR as Determined by IRC Up to approximately 5 years DCR, as determined by the IRC according to RECIST v1.1
6-Month PFS Rate Up to 6 month 6-month PFS rate is defined as the proportion of participants who remained alive and progression-free at 6 months after start of treatment, as determined by the investigator according to RECIST v1.1.
DOR as Determined by IRC Up to approximately 5 years DOR, as determined by the IRC according to RECIST v1.1
Progression Free Survival (PFS) Up to approximately 5 years PFS after start of treatment is defined as the time from start of treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
PFS as Determined by IRC Up to approximately 5 years PFS, as determined by the IRC according to RECIST v1.1
Percentage of Participants With Adverse Events Up to approximately 5 years Percentage of participants with adverse events.
Trial Locations
- Locations (39)
Institut Claudius Regaud
🇫🇷Toulouse, France
Gustave Roussy
🇫🇷Villejuif CEDEX, France
UCSF Helen Diller Family CCC
🇺🇸San Francisco, California, United States
Washington University School of Medicine
🇺🇸Saint 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 Cedex, France
Centre Francois Baclesse
🇫🇷Caen, France
Centre Leon Berard
🇫🇷Lyon, France
Groupe Hospitalier Diaconesses
🇫🇷Paris, France
Centre Eugène Marquis
🇫🇷Rennes, France
Kliniken Essen-Mitte Evang. Huyssens-Stiftung, Klinik für Gynäkologie und gynäkologische Onkologie
🇩🇪Essen, Germany
Universitätsklinikum Mannheim
🇩🇪Mannheim, Germany
Istituto Tumori Napoli
🇮🇹Napoli, Campania, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Lazio, Italy
IRCCS S. Raffaele
🇮🇹Milano, Lombardia, Italy
A.O. U. Consorziale Policlinico di Bari
🇮🇹Bari, Puglia, Italy
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
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
🇪🇸Malaga, Spain
Hôpitaux Universitaires de Genève
🇨🇭Genève, Switzerland
Adana Baskent University Medical Faculty; Oncology
🇹🇷Adana, Turkey
Baskent Universitesi Ankara Hastanesi; Tıbbi Onkoloji Bölümü
🇹🇷Ankara, Turkey
Koc University Medical Faculty; Department of Gynecology & Obstetrics
🇹🇷Istanbul, Turkey
Western General Hospital
🇬🇧Edinburgh, United Kingdom
University College London Hospitals NHS Foundation Trust - University College Hospital
🇬🇧London, United Kingdom