Phase II Study of Rucaparib and Nivolumab in Patients With Leiomyosarcoma

Memorial Sloan Kettering Cancer Center7 sites in 1 country20 target enrollmentNovember 5, 2020

Overview

Brief Summary

The purpose of this study is to find out whether combining the study drugs rucaparib and nivolumab may be an effective treatment for advanced and/or metastatic LMS, and whether the study treatment works as well as the standard chemotherapy for this type of cancer.

Registry

clinicaltrials.gov

Start Date

November 5, 2020

End Date

November 16, 2026

Last Updated

5 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female age ≥ 18 years at the time of informed consent
•Be willing and able to provide written informed consent/assent for the trial
•Be willing to comply with treatment protocol
•Subjects must have a histologically confirmed unresectable/metastatic LMS
•Availability of archival tissue for correlative studies. Either a paraffin block or at least 20 unstained slides are acceptable
•Adequate performance status: ECOG 0 - 2
•Subjects must have had at least 1 but not more than 3 prior lines of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy) for their LMS. Patients who decline the standard of care first-line systemic therapy will be eligible for this trial. Prior adjuvant therapy will not count provided it was completed more than 6 months previously.
•Presence of measurable disease per RECIST v1.
•Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment.
•Adequate organ function determined within 14 days of treatment initiation, defined as per Hematological

Exclusion Criteria

•Uncontrolled intercurrent illness including current active or chronic infection requiring systemic therapy or the following cardiac criteria:
•Symptomatic congestive heart failure (NYHA classification III or IV) within 6 months
•Acute myocardial infarction ≤6 months prior to Day 1
•Grade ≥2 ventricular arrhythmia ≤6 months prior to Day 1
•History of cerebrovascular accident within 6 months before first dose of study drugs
•Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
•Evidence of clinically significant immunosuppression such as the following:
•Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
•Concurrent opportunistic infection
•Receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 7 days prior to enrollment. However, in the setting of non-immune mediated indications for steroid use, chronic/active low dose steroid use may be permitted at the discretion of the principal investigator. The dose of steroid allowed in this setting is also at the discretion of the principal investigator. (Use of inhaled or topical steroids is permitted.)

Arms & Interventions

Rucaparib in combination with Nivolumab

One treatment cycle will consist of 28 days. Patients will receive rucaparib at 600 mg, orally, twice daily, continuously for 28 days. They will receive 480mg of nivolumab intravenously on day 1 of every four-week cycle. This is the recommended phase II dose of the combination therapy. Re-staging scans will be performed every 8 weeks. Treatment will be repeated until the patient develops progressive disease or unacceptable toxicity or for a maximum duration of 26 cycles as long as patients are receiving benefit from treatment, have not had disease progression, met any criteria for study withdrawal and are tolerating therapy.

Intervention: Rucaparib

Rucaparib in combination with Nivolumab

One treatment cycle will consist of 28 days. Patients will receive rucaparib at 600 mg, orally, twice daily, continuously for 28 days. They will receive 480mg of nivolumab intravenously on day 1 of every four-week cycle. This is the recommended phase II dose of the combination therapy. Re-staging scans will be performed every 8 weeks. Treatment will be repeated until the patient develops progressive disease or unacceptable toxicity or for a maximum duration of 26 cycles as long as patients are receiving benefit from treatment, have not had disease progression, met any criteria for study withdrawal and are tolerating therapy.

Intervention: Nivolumab