Phase II Single Arm Study of Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Recurrent, Persistent, or Metastatic Cervical Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Cervical Cancer
- Sponsor
- University of Miami
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Objective Response (OR)
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
The investigators propose to evaluate the efficacy of the combination of standard chemotherapy with bevacizumab with Pembrolizumab in women with recurrent, persistent, or metastatic cervical cancer.
Investigators
Abdulrahman Sinno, MD
Associate Professor of Clinical
University of Miami
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically confirmed recurrent, persistent or metastatic (primary stage IVB) squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy.
- •All patients must have measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.
- •Patients must have recovered from effects of recent surgery or radiotherapy or chemoradiotherapy.
- •Patients should be free of active infections requiring antibiotics (with the exception of uncomplicated urinary tract infection).
- •Tissue from an archival sample or newly obtained core or excisional biopsy of a tumor lesion within 6 weeks confirming diagnosis.
- •Age ≥ 18 years
- •Life expectancy \> 3 months
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Patients must have normal organ and marrow function as defined below:
- •Absolute neutrophil count (ANC) ≥1,500 /microliter (mcL)
Exclusion Criteria
- •Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are ineligible if there is any evidence of other malignancy being present within the last 5 years.
- •Patients who have had prior chemotherapy except when used concurrently with radiation therapy.
- •Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis other than for the treatment of cervical cancer within the last 5 years are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted provided that it was completed more than 3 years prior to registration, and the patient remains free of recurrent or metastatic disease.
- •Patients with an ECOG performance status of 2, 3 or
- •Has received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-PD-L1, or anti-PD-L2 agent.
- •Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Patients with a known history of human immunodeficiency virus (HIV) or active bacillus tuberculosis (TB).
- •Known psychiatric or substance abuse disorders that would interfere with cooperation with requirements of the study
- •Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •History of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis, or history of pneumonitis requiring treatment.
Arms & Interventions
Pembrolizumab, Chemotherapy, Bevacizumab
On day 1 of each 21 day cycle, participants will be administered Pembrolizumab 200mg (IV); Chemotherapy including Paclitaxel 175mg/m2 or 135 mg/m2 (IV), and Cisplatin 50mg/m2 (IV) or Carboplatin area under the curve (AUC) 5; and Bevacizumab 15mg/kg (IV).
Intervention: Pembrolizumab
Pembrolizumab, Chemotherapy, Bevacizumab
On day 1 of each 21 day cycle, participants will be administered Pembrolizumab 200mg (IV); Chemotherapy including Paclitaxel 175mg/m2 or 135 mg/m2 (IV), and Cisplatin 50mg/m2 (IV) or Carboplatin area under the curve (AUC) 5; and Bevacizumab 15mg/kg (IV).
Intervention: Paclitaxel
Pembrolizumab, Chemotherapy, Bevacizumab
On day 1 of each 21 day cycle, participants will be administered Pembrolizumab 200mg (IV); Chemotherapy including Paclitaxel 175mg/m2 or 135 mg/m2 (IV), and Cisplatin 50mg/m2 (IV) or Carboplatin area under the curve (AUC) 5; and Bevacizumab 15mg/kg (IV).
Intervention: Cisplatin
Pembrolizumab, Chemotherapy, Bevacizumab
On day 1 of each 21 day cycle, participants will be administered Pembrolizumab 200mg (IV); Chemotherapy including Paclitaxel 175mg/m2 or 135 mg/m2 (IV), and Cisplatin 50mg/m2 (IV) or Carboplatin area under the curve (AUC) 5; and Bevacizumab 15mg/kg (IV).
Intervention: Carboplatin
Pembrolizumab, Chemotherapy, Bevacizumab
On day 1 of each 21 day cycle, participants will be administered Pembrolizumab 200mg (IV); Chemotherapy including Paclitaxel 175mg/m2 or 135 mg/m2 (IV), and Cisplatin 50mg/m2 (IV) or Carboplatin area under the curve (AUC) 5; and Bevacizumab 15mg/kg (IV).
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Objective Response (OR)
Time Frame: Up to 24 months
Objective response defined as the percentage of patients showing complete or partial response to study therapy. Response to therapy will be evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Secondary Outcomes
- Progression-Free Survival (PFS)(Up to 24 months)
- Overall Survival (OS)(Up to 24 months)
- Number of Participants Experiencing Treatment-Related Toxicity(Up to 15 months)