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

Phase 1

Conditions: Persistent or Recurrent Rare Epithelial Ovarian Tumors
MedDRA 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-IT

Lead Sponsor: F. HOFFMANN - LA ROCHE LTD.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Female

Target Recruitment: 80

Inclusion Criteria

Female aged >=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 (i.e., low-grade serous ovarian cancer, clear cell carcinoma, mucinous carcinoma, carcinosarcoma, undifferentiated carcinoma, seromucinous carcinoma, malignant Brenner tumors, Grades 1 or 2 endometrioid carcinoma, or small cell carcinoma of the ovary, hypercalcemic type) 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 (disease progression within 6 months of last platinum therapy)
At the time of prescreening, submission of a representative tumor specimen that is suitable for central molecular analysis (for mandatory next-generation sequencing (NGS) testing to determine treatment arm assignment). 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 feasible by the investigator, archival tumor tissue obtained within 5 years prior to prescreening may be submitted after confirmation from the Medical Monitor. A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 20 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report prior to study enrollment. The tumor tissue used in the report should be obtained within 5 years prior to prescreening
At the time of prescreening, submission of stained pathology slides, along with the associated pathology report. At least one representative hematoxylin and eosin (H&E)-stained slide demonstrating the histologic cell types will be required. Additional stained slides should be submitted if needed to support the local pathology diagnosis, and additional tissue may be requested if slides do not support the local diagnosis.
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 prior to initiation of study treatment.
For patients in the atezolizumab+bevacizumab (Atezo+Bev) arm not receiving therapeutic anticoagulation: INR <=1.5 and/or aPTT <=1.5* upper limit of normal (ULN) within 7 days prior to initiation of study treatment
For patients in the Atezo+Bev arm receiving therapeutic anticoagulation: use of full-dose oral or parenteral anticoagulants is allowed, if INR and/or aPTT is within therapeutic limits within 7 days prior to initiation of study treatment and anticoagulant regimen has been stable for >=2 weeks prior to initiation of study treatment
Negative HIV test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >=200/microliter, and have an undetectable viral load
Negative HBsAg test at screening
Negative 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 p

Exclusion Criteria

Pregnant or breastfeeding, or intending to become pregnant or breastfeed during study
Primary platinum-refractory disease, defined as progression during or within 4 w 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; non-epithelial ovarian tumors; 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, FIGO Grade 1 or 2, not a high-grade subtype
History of malignancy within 5 y prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, ductal carcinoma in situ, or Stage I uterine cancer
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (1 monthly or more). Patients with indwelling catheters are allowed.
Uncontrolled or symptomatic hypercalcemia
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, outside the CNS.
–The pt has no history of intracranial hemorrhage or spinal cord hemorrhage.
–The pt 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 d prior to initiation of study treatment.
–The pt has no ongoing requirement for corticosteroids as therapy for CNS disease.
–If the pt is receiving anti-convulsant therapy, the dose is considered stable.
History of leptomeningeal disease
Uncontrolled tumor-related pain. Pts requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrollment. Pts 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 should be considered for loco-regional therapy if appropriate prior to enrollment.
Major surgical procedure, other than for diagnosis, within 4 w 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 render the patient at high risk from treatment complications
Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact patient safety
Active infection requiring systemic anti-microbial treatment (including antibiotics, anti-fungal agents, and anti-viral agents)
Treatment with chemotherapy, radiotherapy, antibody therapy or other i

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 progression-free survival (PFS) as determined by the investigator and by the Independent Review Committee<br>To evaluate the efficacy of biomarker-driven treatments based on overall survival (OS) <br>To evaluate the efficacy of biomarker-driven treatments based on confirmed ORR as determined by the Independent Review Committee<br>To evaluate the safety of biomarker-driven treatments<br>To characterize the pharmacokinetic (PK) profile of atezolizumab<br>To evaluate the immune response to 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

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