A Phase II Study of Futibatinib and Pembrolizumab in Metastatic Microsatellite Stable Endometrial Carcinoma

M.D. Anderson Cancer Center1 site in 1 country9 target enrollmentSeptember 30, 2021

ConditionsMetastatic Cancer Endometrium Cancer Endometrial Carcinoma

InterventionsPembrolizumab Futibatinib

DrugsFutibatinib Pembrolizumab

Overview

Phase: Phase 2
Intervention: Pembrolizumab
Conditions: Metastatic Cancer
Sponsor: M.D. Anderson Cancer Center
Enrollment: 9
Locations: 1
Primary Endpoint: To Evaluate the Objective Response Rate (ORR) of Futibatinib and Pembrolizumab in Patients With Metastatic Microsatellite Stable (MSS) Endometrial Carcinoma.
Status: Terminated
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

It's propose this pilot phase 2 study to explore the combination therapy of futibatinib with pembrolizumab in patients with metastatic microsatellite stable (MSS) endometrial carcinoma to provide a well-tolerated regimen for durable responses.

Detailed Description

Primary Objectives * To evaluate the objective response rate (ORR) of futibatinib and pembrolizumab in patients with metastatic microsatellite stable (MSS) endometrial carcinoma. * To evaluate the safety and tolerability. Primary Endpoints * Complete responses (CRs) and partial responses (PRs) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Adverse events (AEs: clinical manifestations and laboratory tests) and serious adverse events (SAEs) according to the NCI Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0.

Registry

clinicaltrials.gov

Start Date

September 30, 2021

End Date

May 6, 2025

Last Updated

7 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

M.D. Anderson Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•To be eligible for this trial, patients must meet all of the following eligibility criteria.
•Patients with histologically confirmed locally advanced or metastatic endometrial carcinoma that is not amenable to curative surgical- or radiation-based intervention, who have received or declined at least one-line systemic chemotherapy.
•Known microsatellite stable (MSS) as pre-identified in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory
•At least one measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.
•Age ≥18 years.
•Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test prior to administration of the first dose of futibatinib within 7 days prior to initiation of therapy (C1D1), and must agree to use effective birth control initiated immediately following negative serum pregnancy test during screening period, during the study, and for at least 180 days after the last dose (or longer based on local requirements). Female patients are not considered to be of child-bearing potential if they are post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
•Adequate organ functions as defined below:
•Absolute neutrophil count (ANC) ≥ 1,000 /μL. Hemoglobin (Hb) ≥ 9 g/dL. Platelets ≥ 75,000 /μL. Total bilirubin ≤ 1.5 x ULN (upper limit of normal); or total bilirubin \< 3 x ULN with direct bilirubin ≤ ULN in patients with well documented Gilbert's Syndrome.
•ALT ≤ 3 x ULN or ≤ 5 x ULN if liver metastases persist. Serum phosphate ≤ 1.5 x ULN. Serum calcium ≤ ULN. Serum albumin ≥ 3 g/dL. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) ≥ 40 mL/min by the Cockcroft-Gault method\* or 24-hour urine collection.
•\*CrCl = (140-age) x (weight \[kg\]) x 0.85 / (72 x serum creatinine mg/dL)

Exclusion Criteria

•Patients who meet any of the following criteria will be not eligible for the study:
•Uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (New York Heart Association Class III or IV), history of myocardial infarction, unstable angina, stroke or transient ischemic attack within 6 months before study enrollment, history or current evidence of uncontrolled ventricular arrhythmia. Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death. Chronic diarrhea diseases considered to be clinically significant in the opinion of the Investigator. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or futibatinib and pembrolizumab administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study.
•History and/or current evidence of any of the following disorders: Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator; Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator; and Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator and a trained ophthalmologist who performs the test.
•Having not recovered from a major surgical procedure or significant traumatic injury (i.e., still needing additional surgical or medical care for these issues): major surgical procedures ≤ 28 days of treatment entry, or minor surgical procedures ≤ 7 days. No waiting period required following port-a-cath or other central venous access placement.
•Unresolved clinically significant Grade 2 toxicity from prior therapy.
•Patient has an inability to swallow oral medications. Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN).
•Clinically active bleeding, or active gastric or duodenal ulcer.
•Fridericia's corrected QT interval (QTcF =QT/∛(60/HR) ) \> 470 ms on ECG conducted during Screening. Patients with an atrioventricular pacemaker or other condition (for example, right bundle branch block) that renders the QT measurement invalid are an exception and the criterion does not apply.
•History of allergic reactions to the study drugs, or any component of the products.
•Currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study. If a patient is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the investigator and the sponsor is required to establish eligibility.

Arms & Interventions

pembrolizumab

Intervention: Pembrolizumab

futibatini

Intervention: Futibatinib

Outcomes

Primary Outcomes

To Evaluate the Objective Response Rate (ORR) of Futibatinib and Pembrolizumab in Patients With Metastatic Microsatellite Stable (MSS) Endometrial Carcinoma.

Time Frame: through study completion, an average of 1 year