A Study to Evaluate the Efficacy and Safety of Biomarker-Driven Therapies in Patients with Persistent or Recurrent Rare Epithelial Ovarian Tumors (BOUQUET)
- Conditions
- Persistent or Recurrent Rare Epithelial Ovarian TumorsMedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: HLTClassification code 10033129Term: Ovarian neoplasms malignant (excl germ cell)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10026669Term: Malignant peritoneal neoplasm NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10033159Term: Ovarian epithelial cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10016180Term: Fallopian tube cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004936-72-DE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 160
• Female, age >=18 years
• Ability to comply with the study protocol
• Persistent or recurrent epithelial ovarian cancer (EOC) that meets the following criteria: a) 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 cancer, clear cell carcinoma, mucinous carcinoma, carcinosarcoma, undifferentiated carcinoma, malignant Brenner tumors,
Grades 1 or 2 endometrioid carcinoma, mesonephric-like adenocarcinoma, and small cell carcinoma of the ovary, hypercalcemic
type). A primary gastrointestinal carcinoma must have been excluded. b)
Disease that is not amenable to curative surgery
• Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors version 1.1 (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:
patients with primary platinum-refractory disease are excluded.
• At the time of prescreening, submission of a representative tumor specimen that is suitable for next-generation sequencing (NGS)
testing and ER IHC to determine treatment arm assignment and for central pathology review. FoundationOne CDx and Ventana SP1 IHC assays may
be considered investigational per local regulations. The tumor sample may be used for exploratory biomarker research. Baseline tumor tissue samples will be collected from all patients, preferably by means of a biopsy performed during prescreening. If a biopsy is not deemed clinically feasible by the investigator, archival tumor tissue obtained within 5 years prior to prescreening may be used. A formalin fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 20 slides containing unstained, freshly cut, serial sections (from the same block) must be submitted along with an associated pathology report prior to study enrollment.
• At the time of prescreening, 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 on the defined laboratory test results, obtained within 14 days (or within 7 days for the
Giredestrant + Abemaciclib arm) prior to initiation of study treatment.
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative hepatitis C virus (HCV) antibody test at screening or positive HCV antibody test followed by a negative HCV RNA test at screening The
HCV RNA test must be performed for patients who have a positive HCV
antibody test
• Positive hepatitis B surface antibody (HBsAb) test at screening or negative HBsAb at screening accompanied by either of the following: a)
Negative total hepatitis B core antibody (HBcAb) b) Positive total HBcAb test followed by a negative (per local laboratory definition) hepatitis B virus (HBV) DNA test
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs (if applicable)
• Patients must meet all general inclusion criteria, as
? Pregnant or breastfeeding, or intending to become pregnant or breastfeed during 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 (formerly considered tumors of low malignant potential)
? Current diagnosis of non-epithelial ovarian tumors (e.g., germ cell tumors, sex cord-stromal tumors)
? Current diagnosis of synchronous primary endometrial cancer
? 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, FIGO Grade 1 or 2, not a high-grade subtype (e.g., papillary serous or clear
cell)
? History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, ductal carcinoma in situ, or Stage I uterine cancer
? Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Patients with indwelling catheters (e.g.,
PleurX) are allowed.
? Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium >12 mg/dL, or corrected calcium > ULN)
? Symptomatic, untreated, or actively progressing CNS metastases. Asymptomatic patients with treated CNS lesions are eligible, provided that all of the following criteria are met:
– Measurable disease, per RECIST v1.1, must be present outside the CNS.
– The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
– The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
– The patient has no ongoing requirement for corticosteroids as therapy for CNS disease.
– If the patient is receiving anti-convulsant therapy, the dose is considered stable.
? History of leptomeningeal disease
? Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
? Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
? Any disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may rende
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: ? To evaluate the efficacy of biomarker-driven treatments based on confirmed objective response rate (ORR) as determined by the investigator;Secondary Objective: ? To evaluate the efficacy of biomarker-driven treatments based on duration of response (DOR), disease control rate (DCR), and<br>progression-free survival (PFS) as determined by the investigator and by the Independent Review Committee and 6-month PFS rate as determined<br>by investigator<br>? To evaluate the efficacy of biomarker-driven treatments based on<br>overall survival (OS)<br>? To evaluate the efficacy of biomarker-driven treatments based on confirmed ORR as determined by the Independent Review Committee Review and 6-month PFS rate as determined by investigator<br>? To characterize the pharmacokinetic (PK) profile of atezolizumab;Primary end point(s): 1. Confirmed ORR as determined by the investigator according to RECIST v1.1;Timepoint(s) of evaluation of this end point: 1. Up to approximately 5 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. DOR as determined by the investigator and IRC according to RECIST<br>v1.1<br>2. DCR as determined by the investigator and IRC according to RECIST<br>v1.1<br>3. PFS as determined by the investigator and IRC according to RECIST<br>v1.1<br>4. Overall survival<br>5. Confirmed ORR, as determined by the IRC according to RECIST v1.1<br>6. 6-month PFS rate as determined by the investigator<br>7. Incidence and severity of adverse events, with severity determined<br>according to National Cancer Institute Common Terminology Criteria for<br>Adverse Events version 5.0 (NCI CTCAE v5.0);Timepoint(s) of evaluation of this end point: 1-7. Up to approximately 5 years<br><br>