Phase II Trial of the PARP Inhibitor Niraparib and PD-1 Inhibitor Dostarlimab in Patients With Advanced Cancers With Active Progressing Brain Metastases (STARLET)

NCT05700721 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-1174NCI-2023-00471
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if the combination of niraparib and dostarlimab can help to control advanced cancer that has spread to the brain.

Conditions

Brain Metastases

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year.

Study Arms (1)

Monotherapy

EXPERIMENTAL

Drug: Niraparib; Drug: Dostarlimab

Interventions

Niraparib DRUG

Given by PO

Also known as: MK-4827

Monotherapy

Dostarlimab DRUG

Given by IV (vein)

Monotherapy

Eligibility Criteria

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

You may qualify if:

• \. Age ≥ 18 years old. 2. Participant must have brain metastasis and either
• \. Advanced BRCA1/2m cancer 2. Advanced HRR-aberrant, non-BRCA1/2m cancer 3. Advanced small cell lung cancer 4. Advanced non-small cell lung cancer 5. Advanced Triple Negative Breast Cancer 3. In cohorts 1 and 2, subjects will be eligible for this study based on the presence of actionable aberrations in one or more of the following HRR genes: BRCA1/2, ATM; BRIP1; CDK12; CHEK1; CHEK2; FANCL; PALB2; RAD51; RAD51B; RAD51C; RAD51D; RAD52; RAD54L, or other related genes at the discretion of the principal investigator in consultation with the MD Anderson Cancer Center Institute for Personalized Cancer Therapy Precision Oncology Decision Support (PODS) group. Variant interpretation for actionability will be performed by PODS.
• \. Any prior SRS to brain lesions or prior excision must have occurred ≥1 week before the start of dosing for this study. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• \. Patients must have had at least one prior line of systemic therapy directed at their malignancy.
• \. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• \. Adequate organ function as described below: (Note: CBC test should be obtained without transfusion or receipt of colony-stimulating factors in the 2 weeks before obtaining).
• Hematological • Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥ 100,000 / mcL
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine ≤1.5xULN OR Measured or calculated creatinine clearance ≥50 mL/min for participants.
• Hepatic
• Serum total bilirubin ≤1.5xULN OR Direct bilirubin ≤1 x ULN for subjects with total bilirubin levels ≥1.5xULN ) (if associated with liver metastases or Gilbert's disease, ≤2.5 x ULN)
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN (if associated with liver metastases, ≤5 x ULN) Coagulation
• International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) ≤1.5xULN, unless subject is receiving anticoagulant therapy.
• \. Participant must have at least one measurable brain metastasis (tumor diameter of 0.5-3 cm by mRECIST on magnetic resonance imaging \[MRI\]) for which all of the following criteria have to be met: asymptomatic (no neurologic signs or symptoms), unirradiated, not requiring immediate local intervention (surgery or radiosurgery), and not requiring systemic glucocorticoid therapy within 10 days prior to study treatment initiation. Patient may have other metastatic lesions which can have had irradiation.

You may not qualify if:

• Participant must not be simultaneously receiving interventional anticancer treatment.
• Participant must not have contraindications to MRI (implanted metal device or foreign bodies) or MRI contrast (insufficient renal function or allergy).
• A history of / or suffers from claustrophobia or subject feels unable to lie flat and still on their back for the required period of time in an MRI or PET/CT scanner.
• Participant must not have symptomatic or untreated spinal cord compression.
• Participant must not have evidence of leptomeningeal disease.
• Participant must not have previously received a combination of PARP inhibitor and PD-1/L1inhibitor. Participant must not have previously received equivalent of full dose single agent PARPi. Prior therapy with PD-1/L1-inhibitor is permitted.
• For participants choosing optional CSF collection via lumbar puncture: no medical contraindication to lumbar puncture may be present (including severe coagulopathy, radiographic concern for impending herniation or obstructive hydrocephalus, or soft tissue infection at puncture site, as outlined in MD Anderson institutional policy). LP may be deferred if at any time the treating physician determines that it would be unsafe to perform this procedure due to the characteristics of the brain metastases (eg. size, associated edema, etc).
• Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
• Participant must not have received systemic anticancer therapy ≤2 weeks prior to initiating protocol therapy.
• Previous systemic radiation therapy encompassing \>20% of the bone marrow (but not encompassing the CNS) within 2 weeks
• Previous stereotactic or highly conformal radiotherapy within 1 week before the start of dosing for this study, whole brain radiotherapy within 2 weeks.
• Participant must not have a known hypersensitivity to niraparib and dostarlimab components or excipients.
• Participants with an inactive, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Participant must not have a history of interstitial lung disease.
• Participants with a major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Brain Neoplasms

Interventions

niraparib; dostarlimab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Timothy Yap, MBBS,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy Yap, MBBS,PHD

CONTACT

(713) 563-1784; tyap@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: January 26, 2023
• Study Start: June 2, 2023
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

US (1)