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

• ClinicalTrials.gov Identifier: NCT04931342
• Recruitment Status: Recruiting
• First Posted: June 18, 2021
• Last Update Posted: May 6, 2023
• Sponsor: Hoffmann-La Roche
• Collaborators: GOG Foundation; European Network of Gynaecological Oncological Trial Groups (ENGOT)
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: June 9, 2021
• First Posted Date: June 18, 2021
• Last Update Posted Date: May 6, 2023
• Actual Study Start Date: October 7, 2021
• Estimated Primary Completion Date: August 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 16, 2021)

Confirmed Objective Response Rate (ORR) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 4, 2023)

• Duration of Response (DOR) [ Time Frame: 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) [ Time Frame: 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.
• Progression Free Survival (PFS) [ Time Frame: 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.
• 6-Month PFS Rate [ Time Frame: 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.
• Overall Survival (OS) [ Time Frame: 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) [ Time Frame: Up to approximately 5 years ]
  Confirmed ORR, as determined by the IRC according to RECIST v1.1.
• DOR as Determined by IRC [ Time Frame: Up to approximately 5 years ]
  DOR, as determined by the IRC according to RECIST v1.1
• DCR as Determined by IRC [ Time Frame: Up to approximately 5 years ]
  DCR, as determined by the IRC according to RECIST v1.1
• PFS as Determined by IRC [ Time Frame: Up to approximately 5 years ]
  PFS, as determined by the IRC according to RECIST v1.1
• Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 5 years ]
  Percentage of participants with adverse events.

Original Secondary Outcome Measures (submitted: June 16, 2021)

• Duration of Response (DOR) [ Time Frame: 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) [ Time Frame: 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.
• Progression Free Survival (PFS) [ Time Frame: 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.
• Overall Survival (OS) [ Time Frame: 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) [ Time Frame: Up to approximately 5 years ]
  Confirmed ORR, as determined by the IRC according to RECIST v1.1.
• DOR as Determined by IRC [ Time Frame: Up to approximately 5 years ]
  DOR, as determined by the IRC according to RECIST v1.1
• DCR as Determined by IRC [ Time Frame: Up to approximately 5 years ]
  DCR, as determined by the IRC according to RECIST v1.1
• PFS as Determined by IRC [ Time Frame: Up to approximately 5 years ]
  PFS, as determined by the IRC according to RECIST v1.1
• Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 5 years ]
  Percentage of participants with adverse events.
• Percentage of Participants With ADA-Positive and ADA-Negative to Atezolizumab [ Time Frame: At baseline and after baseline (up to approximately 5 years) ]
• Number of Participants With ADA-Positive and ADA-Negative to Atezolizumab [ Time Frame: At baseline and after baseline (up to approximately 5 years) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors
• Official Title: A Phase II, Open-Label, Multicenter, Platform Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Ovarian Cancer

Intervention

• Drug: Ipatasertib
  Ipatasertib will be administered by mouth once a day on Days 1-21 of each cycle. (Cycle length = 28 days)
  Other Name: RO5532961
• Drug: Cobimetinib
  Cobimetinib will be administered by mouth once a day on Days 1-21 of each cycle. (Cycle length=28 days)
  Other Name: RO5514041
• Drug: Trastuzumab Emtansine
  Trastuzumab Emtansine will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)
  Other Name: RO5304020
• Drug: Atezolizumab
  Atezolizumab will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)
  Other Name: RO5541267, Tecentriq
• Drug: Bevacizumab
  Bevacizumab will be administered intravenously on Day 1 of each cycle. (Cycle length=21 days)
  Other Name: RO4876646, Avastin
• Drug: Paclitaxel
  Paclitaxel will be administered intravenously on Days 1, 8, and 15 of each cycle. (Cycle length=28 days)
• Drug: Giredestrant
  Giredestrant will be administered by mouth once a day on Days 1-28 of each cycle (Cycle length=28 days)
• Drug: Abemaciclib
  Abemaciclib will be administered by mouth twice a day during each 28-day cycle
• Drug: Inavolisib
  Inavolisib will be administered by mouth once a day on Days 1-28 of each 28-day cycle
• Drug: Palbociclib
  Palbociclib will be administered by mouth once a day on Days 1-21 of each 28-day cycle
• Drug: Letrozole
  Letrozole will be administered by mouth once a day on Days 1-28 of each 28-day cycle
• Drug: Olaparib
  Olaparib will be administered by mouth twice a day on Days 1-28 of each 28-day cycle
• 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.
• Drug: Cyclophosphamide
  Cyclophosphamide will be administered by mouth once a day on Days 1-21 of each cycle. (Cycle length = 21 days)
• Drug: Inavolisib
  Inavolisib will be administered by mouth once a day on Days 1-21 of each 21-day cycle

Study Arms

• Experimental: 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.
  Interventions:

  • Drug: Ipatasertib
  • Drug: Paclitaxel
• Experimental: 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.
  Intervention: Drug: Cobimetinib
• Experimental: 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.
  Intervention: Drug: Trastuzumab Emtansine
• Experimental: 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.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Bevacizumab
• Experimental: 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.
  Interventions:

  • Drug: Giredestrant
  • Drug: Abemaciclib
  • Drug: Luteinizing Hormone-Releasing Hormone (LHRH) Agonists
• Experimental: Inavolisib + Palbociclib (PIK3CA-altered tumors)
  Participants in the Inavolisib + Palbociclib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
  Interventions:

  • Drug: Inavolisib
  • Drug: Palbociclib
• Experimental: 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.
  Interventions:

  • Drug: Inavolisib
  • Drug: Palbociclib
  • Drug: Letrozole
  • Drug: Luteinizing Hormone-Releasing Hormone (LHRH) Agonists
• Experimental: Inavolisib + Olaparib (Non-matched)
  Participants in the Inavolisib + Olaparib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
  Interventions:

  • Drug: Inavolisib
  • Drug: Olaparib
• Experimental: 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.
  Interventions:

  • Drug: Giredestrant
  • Drug: Inavolisib
• Experimental: Inavolisib + Bevacizumab (PIK3CA-altered tumors)
  Participants in the Inavolisib + Bevacizumab arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.
  Interventions:

  • Drug: Bevacizumab
  • Drug: Inavolisib
• Experimental: 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.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Bevacizumab
  • Drug: Cyclophosphamide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 4, 2023): 550
• Original Estimated Enrollment (submitted: June 16, 2021): 200
• Estimated Study Completion Date: September 30, 2026
• Estimated Primary Completion Date: August 15, 2024 (Final data collection date for primary outcome measure)

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)
• In addition to the general inclusion criteria above, participants must meet all of the arm-specific inclusion criteria for the respective arm

General 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
• In addition to the general exclusion criteria above, participants can not meet any of the arm-specific exclusion criteria for the respective arm

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: WO42178 https://forpatients.roche.com/; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

• Listed Location Countries: Australia, Belgium, Canada, Czechia, France, Germany, Italy, Korea, Republic of, Russian Federation, Spain, Switzerland, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT04931342
• Other Study ID Numbers: WO42178; GOG-3051 ( Other Identifier: GOG Foundation ); ENGOT-GYN2 ( Other Identifier: European Network of Gynaecological Oncological Trial Groups (ENGOT) )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current

Collaborators

• GOG Foundation
• European Network of Gynaecological Oncological Trial Groups (ENGOT)

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2023