A Phase II Trial of Irinotecan Liposome and Bevacizumab in Women With Platinum Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Platinum-Resistant Fallopian Tube Carcinoma
- Sponsor
- Northwestern University
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This phase II trial investigates the effect of irinotecan liposome and bevacizumab in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that shows less response to platinum therapy (platinum resistant), has come back (recurrent), or does not respond to treatment (refractory). Irinotecan liposome may help block the formation of growths that may become cancer. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving irinotecan liposome and bevacizumab may kill more cancer cells.
Detailed Description
PRIMARY OBJECTIVE: I. To assess the antineoplastic efficacy of irinotecan sucrosofate (irinotecan liposome) in combination with bevacizumab in women with recurrent, platinum resistant ovarian cancer, as measured by the objective response rate (ORR). SECONDARY EFFICACY OBJECTIVES: I. To determine the overall best response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in women with recurrent, platinum resistant ovarian cancer who have received treatment with irinotecan liposome in combination with bevacizumab. II. To determine the clinical benefit rate (CBR) for irinotecan liposome in combination with bevacizumab in women with recurrent, platinum resistant ovarian cancer. III. To calculate the duration of response (DOR) for irinotecan liposome in combination with bevacizumab in women with recurrent, platinum resistant ovarian cancer. IV. To calculate the duration of stable disease (duration of SD) for irinotecan liposome in combination with bevacizumab in women with recurrent, platinum resistant ovarian cancer. V. To calculate the time to response (TTR) for irinotecan liposome in combination with bevacizumab in women with recurrent, platinum resistant ovarian cancer. VI. To measure median progression-free survival (PFS) in women with recurrent, platinum resistant ovarian cancer who have received treatment with irinotecan liposome in combination with bevacizumab. VII. To measure 16 week progression-free survival (PFS-16) in women with recurrent, platinum resistant ovarian cancer who have received treatment with irinotecan liposome in combination with bevacizumab. SECONDARY SAFETY OBJECTIVE: I. To assess the toxicity profile of irinotecan liposome in combination with bevacizumab in women with recurrent, platinum resistant ovarian cancer according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. OUTLINE: Patients receive bevacizumab intravenously (IV) and irinotecan sucrosofate IV over 90 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then every 6 months for 2 years.
Investigators
Daniela Matei
Daniela Matei, MD
Northwestern University
Eligibility Criteria
Inclusion Criteria
- •Subjects must have histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
- •NOTE: Subjects with carcinosarcoma histology and/or mixed epithelial histology are not eligible.
- •Subjects must have recurrent, platinum resistant or refractory disease, defined as progression \< 6 months after completion of a platinum-based chemotherapy regimen or as persistent disease that remains after completion of a platinum-based therapy
- •Subjects must have measurable disease as assessed by RECIST 1.1
- •Subjects must have received at least 1 but no more than 3 prior platinum-based chemotherapy regimens
- •Subjects must have adequately recovered (in the opinion of the treating investigator) from adverse events due to prior anti-cancer therapy, with the exceptions of any grade alopecia and =\< grade 2 peripheral neuropathy per NCI-CTCAE version 5.0
- •Subjects must be age \>= 18 years
- •Subjects must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Hemoglobin \>= 9.0 g/dL (within =\< 28 days prior to registration)
- •White blood cell (WBC) count \>= 3.0 x 10\^9/L (within =\< 28 days prior to registration)
Exclusion Criteria
- •Exclusions for receipt of prior systemic anti-cancer therapy:
- •Subjects must not have received any prior irinotecan-based therapies.
- •Subjects must not have received more than 3 prior platinum-based chemotherapy regimens.
- •Subjects must not have received more than 2 prior non-platinum, cytotoxic chemotherapy regimens.
- •Note: Prior receipt of non-VEGF-targeting biological therapies is permitted. These may include but are not limited to hormonal therapies, immunotherapies, monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs), poly (ADP-ribose) polymerase (PARP) inhibitors, or other targeted agents. Refer to the below exclusion criterion for washout rules
- •Exclusions for washout from prior systemic anti-cancer therapy:
- •Subjects must not have received chemotherapy, immunotherapy, monoclonal antibody (mAb) therapy, hormonal therapy, or other targeted therapy within =\< 14 days prior to registration.
- •Subjects must not have received investigational agents or investigational devices within =\< 14 days prior to registration.
- •Subjects must not have received VEGF-targeting agents, including bevacizumab, within =\< 6 months prior to registration
- •Subjects must not have received prior radiotherapy to the pelvis or abdomen within =\< 3 months prior to registration. Subjects must not have received prior radiotherapy to other areas within =\< 14 days prior to registration
Arms & Interventions
Treatment (bevacizumab, irinotecan sucrosofate)
Patients receive bevacizumab IV and irinotecan sucrosofate IV over 90 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Treatment (bevacizumab, irinotecan sucrosofate)
Patients receive bevacizumab IV and irinotecan sucrosofate IV over 90 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Irinotecan Sucrosofate
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: Up to 5 months
Defined as the proportion of treated subjects who experience an objective response, confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Complete Response (CR) = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD) = Neither sufficient shrinkage to qualify
Secondary Outcomes
- Overall Best Response(Approximately 29 Weeks)
- Duration of Stable Disease(Approximately 29 Weeks)
- Time to Response (TTR)(Approximately 29 Weeks)
- Progression Free Survival(At 16 weeks)
- Number of Observed Serious and Other (Not Including Serious) Adverse Events(Approximately 29 Weeks)
- Clinical Benefit Rate (CBR)(Approximately 29 Weeks)
- Duration of Response (DOR)(Approximately 29 Weeks)
- Median Progression-Free Survival (PFS)(Approximately 29 Weeks)