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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Given IV
Given IV
Northwestern University
Chicago, Illinois, United States
Objective Response Rate (ORR)
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
Time frame: Up to 5 months
Overall Best Response
Will tabulate the proportion of subjects who experience each the following as their best response to trial therapy: CR, PR, stable disease (SD), progressive disease (PD) or not evaluable (NE) per 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
Time frame: Approximately 29 Weeks
Clinical Benefit Rate (CBR)
To determine the CBR, this endpoint will calculate the proportion of treated, evaluable subjects who experience clinical benefit from trial therapy. Clinical benefit is defined as confirmed complete response (CR); confirmed partial response (PR); or stable disease (SD) for ≥ 4 months (calculated from the initiation of trial therapy on C1D1) per RECIST 1.1.16. Will tabulate the proportion of subjects who experience each of the following as their best response to trial therapy: CR, PR, stable disease (SD), progressive disease (PD) or not evaluable (NE) per RECIST 1.1. CBR data will be collected from baseline until the subject experiences disease progression initiates subsequent anti-cancer therapy, or completes study participation (whichever occurs first).
Time frame: Approximately 29 Weeks
Duration of Response (DOR)
To calculate the DOR for the combination of irinotecan liposome and bevacizumab, this endpoint will be calculated as the time that elapsed between the day of first documented response to trial therapy (CR or PR, whichever is first recorded) and subsequent disease progression (taking as reference for progressive disease the smallest tumor measurements recorded on study). For DOR analysis, response is defined as complete response (CR) or partial response (PR) per RECIST 1.1; and disease progression is defined as progressive disease (PD) per RECIST 1.1.16 DOR data will be collected from the time of first response to trial therapy until the subject experiences disease progression, initiates subsequent anti-cancer therapy, or completes study participation (whichever occurs first). If disease progression is not observed prior to initiating subsequent anti-cancer therapy or completing study participation, the DOR will be censored as the last available disease assessment.
Time frame: Approximately 29 Weeks
Duration of Stable Disease
To calculate the Duration of SD (CR, PR, and SD) for the combination of irinotecan liposome and bevacizumab, this endpoint will be calculated as the time that elapsed between the day of initiation of trial therapy and subsequent disease progression (taking as reference for progressive disease the smallest measurements recorded on study). Duration of SD analysis will capture subjects who achieve a best response of CR, PR, or SD, as defined per RECIST 1.1. For Duration of SD analysis, disease progression is defined as progressive disease (PD) per RECIST 1.1. Duration of SD data will be collected from baseline until the subject experiences disease progression, initiates subsequent anti-cancer therapy, or completes study participation. If disease progression is not observed prior to initiating subsequent anti-cancer therapy or completing study participation, the Duration of SD will be censored as the last available disease assessment.
Time frame: Approximately 29 Weeks
Time to Response (TTR)
For TTR analysis, a response to therapy is defined as a confirmed complete response (CR) or confirmed partial response (PR) per RECIST 1.1.
Time frame: Approximately 29 Weeks
Median Progression-Free Survival (PFS)
This endpoint will calculate the progression-free survival time as the time that elapsed between the initiation of trial therapy (C1D1) and the day of first documented disease progression or death from any cause for all evaluable subjects. Per RECIST 1.1, 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).
Time frame: Approximately 29 Weeks
Progression Free Survival
This endpoint will be calculated based on the proportion of subjects who are alive and progression-free at 16 weeks after initiating trial therapy. Per RECIST 1.1, 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).
Time frame: At 16 weeks
Number of Observed Serious and Other (Not Including Serious) Adverse Events
Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 (NCI-CTCAE v5.0).
Time frame: Approximately 29 Weeks
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