A Randomized Phase II Induction Discontinuation Trial of Emactuzumab Following Paclitaxel and Bevacizumab in Patients With Platinum-Resistant, Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Fallopian Tube Adenocarcinoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 9
- Locations
- 8
- Primary Endpoint
- Part 1: To Evaluate the Safety of Administration of Paclitaxel, Bevacizumab and Emactuzumab Over 4 Weeks.
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This randomized phase II trial studies the side effects of paclitaxel and bevacizumab with or without emactuzumab and how well they work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back after treatment with platinum chemotherapy. Monoclonal antibodies, such as emactuzumab, block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab may prevent the growth of new blood vessels that tumors need to grow. Giving emactuzumab with paclitaxel and bevacizumab may work better in treating ovarian, fallopian tube, or primary peritoneal cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the safety of administration of paclitaxel, bevacizumab and emactuzumab over 4 weeks. (Part 1) II. To compare the progression-free survival (PFS) of patients with stable disease following Part 2A randomized to paclitaxel plus bevacizumab or to paclitaxel, bevacizumab plus emactuzumab. (Part 2B) SECONDARY OBJECTIVES: I. To estimate the progression-free survival (PFS) of the treatment arms. II. Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) and CA-125 response criteria ("responders"). III. Objective response rate by RECIST only ("RECIST responders"). IV. Objective response rate by CA-125 response criteria only ("CA-125 responders"). V. Biological progression-free interval (PFIbio) by serum CA-125 assessed according to the Gynecologic Cancer Intergroup (GCIG) criteria. VI. Overall survival (OS). VII. Safety and tolerability. VIII. To characterize the pharmacokinetics of bevacizumab and emactuzumab when administered in combination. EXPLORATORY OBJECTIVES: I. To assess the utility of surrogate biomarkers and the anti-tumor response to therapy with the combination treatment of bevacizumab and emactuzumab. II. To assess tumor alterations by serial non-invasive imaging macrophage-specific imaging, ADC (apparent diffusion coefficient) for cellularity, and DCE (dynamic contrast enhanced) for vasculature. OUTLINE: Patients receive paclitaxel intravenously (IV) over 60 minutes on days 1, 8, 15, and 22 and bevacizumab IV over 90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unexpected toxicity. Patients with stable disease are randomized to 1 of 2 arms. ARM I: Patients receive paclitaxel IV over 60 minutes on days 1, 8, 15, and 22 and bevacizumab IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive paclitaxel and bevacizumab as in Arm I. Patients also receive emactuzumab IV over 30 minutes on days 1 and 15. Courses 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 2 years, every 4 months for 1 year, and then every 6 months for 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient's awareness and willingness to comply with the study requirements (inclusive of 2 biopsies, one at baseline and if they qualify, one pre-randomization for part 2B)
- •Women 18 years of age or older
- •Histologically confirmed and documented disease to include: adenocarcinoma NOS (not otherwise specified), clear cell adenocarcinoma, endometrioid adenocarcinoma, malignant Brenner's tumor, mixed epithelial carcinoma, mucinous adenocarcinoma, serous adenocarcinoma, transitional cell carcinoma, and undifferentiated carcinoma
- •Patients must have platinum-resistant disease, (defined as progression within \< 6 months from completion of a minimum of 4 platinum therapy cycles (+ 7 days); the date should be calculated from the last administered dose of platinum therapy)
- •Patients must have disease that is measurable according to RECIST 1.1 or assessable according to the GCIG CA-125 criteria and require chemotherapy treatment; part 1: patients must have one or more measurable target lesion; part 2: patients must have two or more measurable target lesions; measurable disease is defined at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each 'target' lesion must be \>= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or \>= 10 mm when measured by spiral CT
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- •Newly obtained core or excisional biopsy of a tumor lesion for part 2A and if they qualify, one pre-randomization biopsy for part 2B
- •Absolute neutrophil count \>= 1,500/mcL
- •Platelets \>= 100,000/mcL
- •Hemoglobin \>=9 g/dL or \>= 5.6 mmol/L
Exclusion Criteria
- •Patients who have disease progression prior to completion of intended frontline therapy, including patients demonstrating disease progression after interval cytoreduction
- •Non-epithelial, including malignant mixed Mullerian tumors
- •Ovarian tumors with low malignant potential (i.e. borderline tumors)
- •For part 2 patients only: History of other clinically active malignancy within 5 years of enrollment, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix or breast, or early stage endometrial cancer (stage IA/B, grade 1 or 2, endometrioid histology)
- •Previous treatment with \> 2 anticancer regimens for ovarian cancer
- •Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment, with the following exceptions: hormone-replacement therapy or oral contraceptives; tyrosine kinase inhibitors (TKIs) that have been discontinued \> 7 days prior to cycle 1, day 1; screening scans must be obtained after discontinuation of prior TKIs
- •Any prior radiotherapy to the pelvis or abdomen
- •Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study; minor surgical procedures including placement of a vascular access device, within 2 days of the first study treatment
- •Previous exposure to murine CA-125 antibody (only applicable to those patients with non-measurable disease by RECIST)
- •Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (\> 325 mg/day)
Arms & Interventions
Arm I (paclitaxel, bevacizumab)
Patients receive paclitaxel IV over 60 minutes on days 1, 8, 15, and 22 and bevacizumab IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Arm I (paclitaxel, bevacizumab)
Patients receive paclitaxel IV over 60 minutes on days 1, 8, 15, and 22 and bevacizumab IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm I (paclitaxel, bevacizumab)
Patients receive paclitaxel IV over 60 minutes on days 1, 8, 15, and 22 and bevacizumab IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Paclitaxel
Arm II (paclitaxel, bevacizumab, emactuzumab)
Patients receive paclitaxel and bevacizumab as in Arm I. Patients also receive emactuzumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Arm II (paclitaxel, bevacizumab, emactuzumab)
Patients receive paclitaxel and bevacizumab as in Arm I. Patients also receive emactuzumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Emactuzumab
Arm II (paclitaxel, bevacizumab, emactuzumab)
Patients receive paclitaxel and bevacizumab as in Arm I. Patients also receive emactuzumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm II (paclitaxel, bevacizumab, emactuzumab)
Patients receive paclitaxel and bevacizumab as in Arm I. Patients also receive emactuzumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Paclitaxel
Arm II (paclitaxel, bevacizumab, emactuzumab)
Patients receive paclitaxel and bevacizumab as in Arm I. Patients also receive emactuzumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Pharmacological Study
Outcomes
Primary Outcomes
Part 1: To Evaluate the Safety of Administration of Paclitaxel, Bevacizumab and Emactuzumab Over 4 Weeks.
Time Frame: Up to 4 weeks
Safety is defined as no required dose alterations during the first cycle (4 weeks) of therapy due to a grade 3 or greater related adverse event.
Part 2B: To Compare the Progression-free Survival (PFS) of Patients With Stable Disease Following Part 2A Randomized to Paclitaxel Plus Bevacizumab or to Paclitaxel, Bevacizumab Plus Emactuzumab.
Time Frame: At 32 weeks
Will use a log-rank test.