- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03367871
Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Cervical Cancer
August 23, 2023 updated by: University of Miami
Phase II Single Arm Study of Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Recurrent, Persistent, or Metastatic Cervical Cancer
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
17
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Marilyn Huang, MD, MS
- Phone Number: 305-243-2233
- Email: m.huang@med.miami.edu
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33136
- University of Miami
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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) 1.1.
- 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 /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
- Albumin ≥ 2.5 mg/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
- Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
- Negative urine or serum pregnancy ≤72 hours (i.e. 3 days) prior to receiving the first dose of study medication if not surgically sterilized. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential (i.e., have not been surgically sterilized or have not been without menses for >1 year) should be willing to use 2 methods of birth control at the same time, be surgically sterile, or abstain from heterosexual activity for the course of the study and at least 120 days after the last study dose.
- Ability to understand and the willingness to sign a written informed consent document.
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 4.
- Has received prior therapy with an anti-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 (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.
- Patients who are adults and unable to consent, who are not yet adults, pregnant and nursing women, and prisoners are ineligible.
- Has an active infection requiring systemic therapy.
- Thromboembolism (either arterial or venous) within 6 weeks of initiation of treatment.
- Has significant cardiovascular disease, such as New York Heart Association cardiac disease classification of Class II or greater, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmias, or unstable angina. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction <50% must be on a stable medical regimen that is optimized in the opinion of the treating physician in consultation with a cardiologist if appropriate.
- Has undergone major surgical procedure within 28 days prior to first Bevacizumab dose or anticipation of the need for a major surgical procedure during the course of the study.
- Has proteinuria, as demonstrated by urine dipstick or >2.0 g of protein in a urine protein-to creatinine ratio and/or 24 hour (hr) urine collection. All patients with ≥ 2+ protein on dipstick urinalysis at baseline must undergo a urine-to-protein ratio and/or 24 hr urine collection and demonstrate < 2.0 g of protein.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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 AUC 5; and Bevacizumab 15mg/kg (IV).
|
IV
Other Names:
Administered intravenously (IV) on day 1
Other Names:
Administered intravenously (IV) on day 1
Other Names:
Administered intravenously (IV) on day 1
Other Names:
Administered intravenously (IV) on day 1
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: Up to 24 months
|
Objective response defined as the proportion 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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-Free Survival (PFS)
Time Frame: Up to 24 months
|
Rate of Progression-Free Survival (PFS) in study participants.
PFS is defined as the time from start of treatment until documented disease progression or death (by any cause, in the absence of progression).
In alive, progression-free patients, PFS will be censored at the last evaluable tumor assessment.
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Up to 24 months
|
Overall Survival (OS)
Time Frame: Up to 24 months
|
Rate of Overall Survival (OS) in study participants.
OS is defined as the time from start of treatment until death due to any cause.
|
Up to 24 months
|
Proportion of Participants Experiencing Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to 15 months
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The safety and tolerability profile of the study therapy will be determined by the proportion of study participants experiencing treatment-related adverse events (AEs) and serious adverse events (SAEs).
Treatment-related AEs and SAEs will be evaluated with respect to grade and relationship to treatment, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03.
|
Up to 15 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Marilyn Huang, MD, MS, University of Miami
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 6, 2018
Primary Completion (Actual)
January 30, 2023
Study Completion (Actual)
January 30, 2023
Study Registration Dates
First Submitted
December 5, 2017
First Submitted That Met QC Criteria
December 5, 2017
First Posted (Actual)
December 11, 2017
Study Record Updates
Last Update Posted (Actual)
August 25, 2023
Last Update Submitted That Met QC Criteria
August 23, 2023
Last Verified
August 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Cervical Diseases
- Uterine Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Uterine Cervical Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Immune Checkpoint Inhibitors
- Carboplatin
- Paclitaxel
- Bevacizumab
- Pembrolizumab
Other Study ID Numbers
- 20170846
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cervical Cancer
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University of California, San DiegoWithdrawnCervical Cancer | Cervical Cancer Stage | Cervical Cancer Stage IB2 | Cervical Cancer Stage IB1 | Cervical Cancer Stage I | Cervical Cancer Stage IB | Cervical Cancer Stage II | Cervical Cancer Stage IIa | Cervical Cancer, Stage IIB | Cervical Cancer, Stage III | Cervical Cancer Stage IIIB | Cervical Cancer... and other conditionsUnited States
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M.D. Anderson Cancer CenterWithdrawnStage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical Cancer FIGO 2018 | Stage IIB Cervical Cancer FIGO 2018 | Stage III Cervical Cancer FIGO 2018 | Stage IIIA Cervical Cancer FIGO... and other conditions
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Abramson Cancer Center of the University of PennsylvaniaWithdrawnCervical Cancer | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer
-
National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical CancerUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IA Cervical Cancer | Stage IB Cervical Cancer | Stage IA1 Cervical Cancer | Stage IA2 Cervical Cancer | Stage IB1 Cervical Cancer | Stage IB2 Cervical Cancer | Stage IB3 Cervical CancerUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingCervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma, Not Otherwise Specified | Recurrent Cervical Carcinoma | Stage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical... and other conditionsUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical CancerUnited States
-
Shanghai First Maternity and Infant HospitalNot yet recruitingCervical Cancer, Stage IIB | Cervical Cancer Stage IIIB | Cervical Cancer Stage IIIA | Cervical Cancer, Stage IVA
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University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical Cancer | Stage IIIA Cervical Cancer | Stage IIIB Cervical CancerUnited States
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National Cancer Institute (NCI)Gynecologic Oncology Group; NCIC Clinical Trials GroupTerminatedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Cervical Adenosquamous Cell CarcinomaUnited States, Canada
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