Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Cervical Cancer

NCT03367871 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 20170846
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Cervical Cancer

Keywords

Recurrent Cervical Cancer; Persistent Cervical Cancer; Metastatic Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response (OR)

  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).

  Up to 24 months

Secondary Outcomes (3)

• 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

Study Arms (1)

Pembrolizumab, Chemotherapy, Bevacizumab

EXPERIMENTAL

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).

Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Cisplatin; Drug: Carboplatin; Drug: Bevacizumab

Interventions

Pembrolizumab DRUG

IV

Also known as: MK-3475, Keytruda

Pembrolizumab, Chemotherapy, Bevacizumab

Paclitaxel DRUG

Administered intravenously (IV) on day 1

Also known as: Taxol

Pembrolizumab, Chemotherapy, Bevacizumab

Cisplatin DRUG

Administered intravenously (IV) on day 1

Also known as: Platinol

Pembrolizumab, Chemotherapy, Bevacizumab

Carboplatin DRUG

Administered intravenously (IV) on day 1

Also known as: Paraplatin

Pembrolizumab, Chemotherapy, Bevacizumab

Bevacizumab DRUG

Administered intravenously (IV) on day 1

Also known as: Avastin

Pembrolizumab, Chemotherapy, Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) 1.1.
• 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)
• Platelets ≥ 100,000 / mcL
• Hemoglobin ≥ 8 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR Measured or calculated a creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥ 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN. Creatinine clearance should be calculated per institutional standard.
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases

You may not qualify if:

• 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 4.
• 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.
• Is pregnant, breastfeeding or expecting to conceive within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (HCV) (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• Received live vaccine within 30 days prior to the first dose of study treatment. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however. intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed.
• Patient with known hypersensitivity to Pembrolizumab or any of its excipients (active ingredients).
• Patient receiving concurrent additional biologic therapy.

Sponsors & Collaborators

• University of Miami: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

pembrolizumab; Paclitaxel; Cisplatin; Carboplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Abdulrahman Sinno MD
• Organization: University of Miami

ak.sinno@med.miami.edu

+1 (305) 243-2233

Study Officials

• Marilyn Huang, MD, MS

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: December 11, 2017
• Study Start: September 6, 2018
• Primary Completion: January 30, 2023
• Study Completion: January 30, 2023
• Last Updated: June 18, 2024
• Results First Posted: June 18, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)