A Phase 2 Study of Atezolizumab (MPDL3280A) in Combination With Bevacizumab in Patients With Recurrent, Persistent or Metastatic Cervical Cancer
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- Cervical Adenocarcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 11
- Locations
- 22
- Primary Endpoint
- Number of Participants With Objective Response Rate (ORR, Either Partial or Complete Response) Defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Criteria
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This phase II trial studies how well atezolizumab and bevacizumab work in treating patients with cervical cancer that has come back, remains despite treatment, or has spread to other places in the body. Monoclonal antibodies, such as atezolizumab and bevacizumab, may shrink tumor cell and interfere with the ability of tumor cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the anti-tumor activity (proportion of patients with objective response by Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\] criteria) of atezolizumab and bevacizumab in patients with recurrent, persistent or metastatic cervical cancer. SECONDARY OBJECTIVES: I. To estimate the duration of progression free survival (PFS) and overall survival (OS). II. To assess safety by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0). III. To describe the efficacy of the combination of atezolizumab and bevacizumab as measured by objective response, by PD-L1 expression on tumor and immune cells measured by semi-quantitative immunohistochemistry (IHC). IV. To describe the efficacy of the combination of atezolizumab and bevacizumab as measured by objective response, by intratumoral and peripheral T-cell receptor (TCR) clonality and tumor infiltrating lymphocyte proportion. OUTLINE: Patients receive atezolizumab intravenously (IV) over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have measurable disease per RECIST 1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as \>= 10 mm (\>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; to be considered pathologically enlarged and measurable, a lymph node must be \>= 15 mm (\>= 1.5 cm) in short axis
- •Patients must have had one prior systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix (e.g.; paclitaxel/cisplatin, paclitaxel/cisplatin/bevacizumab), at least one which must have contained bevacizumab
- •NOTE: Patients are allowed to receive 1-2 prior regimens for management of recurrent, persistent or metastatic carcinoma of the cervix; patients who have received more than two prior systemic regimens for management of recurrent, persistent or metastatic carcinoma of the cervix are NOT eligible
- •NOTE: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix; adjuvant therapy includes cisplatin given concurrent with primary radiation therapy (CCRT) and adjuvant chemotherapy given following the completion of concurrent chemotherapy and radiation therapy (e.g., paclitaxel and carboplatin for up to 4 cycles)
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- •Absolute neutrophil count \>= 1,500/mcL
- •Platelets \>= 100,000/mcL
- •Hemoglobin \>= 9 g/dL
- •Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN
Exclusion Criteria
- •Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier; however, the following therapies are allowed:
- •Hormone-replacement therapy or oral contraceptives
- •Herbal therapy \> 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)
- •Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- •Prior treatment with anti-CTLA-4 therapeutic antibody or pathway-targeting agents
- •Treatment with any other investigational agent within 4 weeks prior to cycle 1, day 1
- •Treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-alpha or interleukin \[IL\]-2) within 6 weeks prior to cycle 1, day 1
- •Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to cycle 1, day 1
- •Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
Arms & Interventions
Treatment (atezolizumab, bevacizumab)
Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Atezolizumab
Treatment (atezolizumab, bevacizumab)
Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Treatment (atezolizumab, bevacizumab)
Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
Number of Participants With Objective Response Rate (ORR, Either Partial or Complete Response) Defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Criteria
Time Frame: Up to 2 years
Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Complete Response (CR) is the disappearance of all lesions and Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) is CR+PR.
Secondary Outcomes
- Progression Free Survival(From start of treatment to investigator determined date of progression, or death due to any cause, whichever occurs first, assessed up to 2 years)
- Overall Survival (OS)(From start of treatment to death, assessed up to 2 years)
- Intratumoral and Peripheral T-cell Receptor (TCR) Clonality Assessed by TCR Sequencing(Up to 2 years)
- Percent of Participants With Adverse Events(Up to 30 days after the last dose of study treatment, on average of 4 months)
- PD-L1 Expression on Tumor and Immune Cells Measured by Semi-quantitative Immunohistochemistry(Up to 2 years)