Phase II Investigation of Pembrolizumab in Combination With Bevacizumab and Oral Cyclophosphamide in Patients With High Grade Ovarian Cancer and Surgically Documented Minimal Residual Disease After Frontline Therapy

M.D. Anderson Cancer Center2 sites in 1 country20 target enrollmentDecember 12, 2023

ConditionsOvarian Cancer

InterventionsPembrolizumab Bevacizumab Cyclophosphamide

Overview

Phase: Phase 2
Intervention: Pembrolizumab
Conditions: Ovarian Cancer
Sponsor: M.D. Anderson Cancer Center
Enrollment: 20
Locations: 2
Primary Endpoint: Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Status: Recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

To find out if combining pembrolizumab, bevacizumab (or an equivalent biosimilar drug), and low-dose cyclophosphamide can help control high-grade ovarian cancer that has MRD after treatment. The safety of this treatment combination will also be studied.

Detailed Description

Primary Objectives 1\. To determine whether the combination of pembrolizumab, bevacizumab (or equivalent biosimilars) and oral low dose cyclophosphamide can improve PFS by 6 months (compared to historical control/current trial) in patients with high grade ovarian cancer with residual disease identified by second look laparoscopy. Secondary Objectives 1\. To determine the safety of the above regimen in this patient population. Exploratory Objectives 1. Correlating clinical benefit with gene expression and immune profiles of tumor tissue from SLL and confirmatory biopsy at the time of radiological progression. 2. Tumor cell free tumor DNA (ctDNA) is emerging as a potentially sensitive marker of response in patients undergoing immunotherapy treatment(Lee et al. 2018). We will compare serial plasma ctDNA levels with response by RECIST v1.1.

Registry

clinicaltrials.gov

Start Date

December 12, 2023

End Date

September 30, 2027

Last Updated

last month

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

M.D. Anderson Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of high grade non-mucinous epithelial ovarian cancer will be enrolled in this study.
•A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
•Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR
•A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days after the last dose of study medication.
•The participant provides written informed consent for the trial.
•Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
•Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
•Have received standard of care frontline surgical and chemotherapy treatment (at least six cycles of platinum and taxane (or equivalent, with or without bevacizumab/biosimilar therapy). Patients who received neoadjuvant therapy are included. Omission of one or more doses of chemo for toxicity or hypersensitivity reaction is allowed. Have minimal residual disease (MRD) after a complete clinical response to frontline therapy (defined as: having a normalization of CA-125 and no obvious evidence of disease on exam or imaging unless the patient has an elevated CA-125 thought to be due to other confounding causes by the treating physician). Imaging with subtle or indeterminate findings will not disqualify participation.
•Having MRD is defined as either of the following conditions (must occur within 3 months on the last dose of frontline platinum-taxane chemotherapy):
•Second-look surgery that may be performed either as standard of care or in the context of a non-therapeutic clinical trial with positive tissue or cytology.

Exclusion Criteria

•Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
•Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
•Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
•Is currently receiving or has received an investigational agent within 4 weeks prior to the first dose of study intervention.
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Steroids to reduce risk of radiologic contrast allergy is permitted.
•Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
•Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
•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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, type I diabetes mellitus, etc.) is not considered a form of systemic treatment and is allowed.
•Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
•Serious active infection that in the opinion of treating physician would preclude participation.

Arms & Interventions

Pembrolizumab in Combination with Bevacizumab and Oral Cyclophosphamide

Participants will begin receiving the study drug Pembrolizumab in Combination with Bevacizumab and Oral Cyclophosphamide. Each study cycle is 21 days.

Intervention: Pembrolizumab

Pembrolizumab in Combination with Bevacizumab and Oral Cyclophosphamide

Participants will begin receiving the study drug Pembrolizumab in Combination with Bevacizumab and Oral Cyclophosphamide. Each study cycle is 21 days.

Intervention: Bevacizumab

Pembrolizumab in Combination with Bevacizumab and Oral Cyclophosphamide

Participants will begin receiving the study drug Pembrolizumab in Combination with Bevacizumab and Oral Cyclophosphamide. Each study cycle is 21 days.

Intervention: Cyclophosphamide