A Study of Rucaparib and Nivolumab in People With Leiomyosarcoma

NCT04624178 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 20-358
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

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.

Conditions

Leiomyosarcoma

Keywords

Rucaparib; Nivolumab; 20-358

Outcome Measures

Primary Outcomes (1)

• Best objective response rate

  as assessed by RECIST 1.1

  by 24 weeks

Secondary Outcomes (1)

• Progression free survival (PFS)

  at 24 weeks

Study Arms (1)

Rucaparib in combination with Nivolumab

EXPERIMENTAL

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.

Drug: Rucaparib; Drug: Nivolumab

Interventions

Rucaparib DRUG

Rucaparib at 600 mg, orally, twice daily, continuously for 28 days.

Rucaparib in combination with Nivolumab

Nivolumab DRUG

Nivolumab 480mg intravenously on day 1 of every four-week cycle.

Rucaparib in combination with Nivolumab

Eligibility Criteria

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

You may qualify if:

• 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 v1.1. 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
• Absolute neutrophil count (ANC) ≥1.5 K/mcL
• Platelets ≥100 K/ mcL
• Hemoglobin ≥9 g/dL Renal
• Serum creatinine OR Measured or calculated creatinine clearance Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2. For calculated CrCL, the Cockcroft Gault formula or institutional standard formula can be used.
• Hepatic
• Serum total bilirubin \<1.5 X ULN OR \<2 X ULN if hyperbilirubinemia is due to Gilbert's syndrome

You may not qualify if:

• 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.)
• History or evidence of symptomatic autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 years prior to enrollment. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease.
• Known history of a positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• History of non-viral hepatitis or cirrhosis
• A history of alcohol abuse
• Use of any live vaccines (e.g., against infectious diseases such as varicella) within 4 weeks (28 days) of initiation of study therapy

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• Clovis Oncology, Inc.: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Limited protocol activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leiomyosarcoma

Interventions

rucaparib; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sujana Movva, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a Phase II open label study evaluating the combination of rucaparib and nivolumab in patients with refractory LMS.

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 10, 2020
• Study Start: November 5, 2020
• Primary Completion (Estimated): November 16, 2026
• Study Completion (Estimated): November 16, 2026
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (7)