This study will evaluate the efficacy and safety of multiple biomarker-driven 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.
Not yet recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Ipatasertib | RO5532961 | Ipatasertib + Paclitaxel |
| Cobimetinib | RO5514041 | Cobimetinib |
| Trastuzumab Emtansine | RO5304020 | Trastuzumab Emtansine |
| Atezolizumab | RO5541267, Tecentriq | Atezolizumab + Bevacizumab |
| Bevacizumab | RO4876646, Avastin | Atezolizumab + Bevacizumab |
| Paclitaxel | Ipatasertib + Paclitaxel |
| Name | Type | Description | Interventions |
|---|---|---|---|
| Ipatasertib + Paclitaxel | Experimental | Participants in the Ipatasertib + Paclitaxel arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. |
|
| Cobimetinib | Experimental | Participants in the Cobimetinib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. |
|
| Trastuzumab Emtansine | Experimental | Participants in the Trastuzumab Emtansine arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1. |
|
| Atezolizumab + Bevacizumab | 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. |
|
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 (i.e., low-grade serous ovarian
carcinoma, 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);
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
- Platinum-resistant disease (disease progression within 6 months of last platinum
therapy)
- Submission of a representative tumor specimen that is suitable for central molecular
analysis (for mandatory NGS testing to determine treatment arm assignment)
- Submission of stained pathology slides, along with the associated pathology report
(for central pathology review)
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Adequate hematologic and end-organ function
- Female of childbearing potential must be willing to comply with adequate contraception
- 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 must meet all of the
arm-specific exclusion criteria for the respective arm
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
| Measure: | Confirmed Objective Response Rate (ORR) |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Duration of Response (DOR) |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Disease Contral Rate (DCR) |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall Survival (OS) |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | OS after start of treatment is defined as the time from start of treatment to death from any cause. |
| Measure: | Confirmed ORR as Determined by IRC (Independent Review Committee) |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | Confirmed ORR, as determined by the IRC according to RECIST v1.1. |
| Measure: | DOR as Determined by IRC |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | DOR, as determined by the IRC according to RECIST v1.1 |
| Measure: | DCR as Determined by IRC |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | DCR, as determined by the IRC according to RECIST v1.1 |
| Measure: | PFS as Determined by IRC |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | PFS, as determined by the IRC according to RECIST v1.1 |
| Measure: | Percentage of Participants With Adverse Events |
| Time Frame: | Up to approximately 5 years |
| Safety Issue: | |
| Description: | Percentage of participants with adverse events. |
| Measure: | Percentage of Participants With ADA-Positive and ADA-Negative to Atezolizumab |
| Time Frame: | At baseline and after baseline (up to approximately 5 years) |
| Safety Issue: | |
| Description: |
| Measure: | Number of Participants With ADA-Positive and ADA-Negative to Atezolizumab |
| Time Frame: | At baseline and after baseline (up to approximately 5 years) |
| Safety Issue: | |
| Description: |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | Hoffmann-La Roche |
August 4, 2021
