Niraparib + Carboplatin for Solid Cancers

Recruiting in Palo Alto (17 mi)

+4 other locations

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Georgetown University

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This is a multi-institutional Phase I dose-escalation and dose-expansion trial for patients with advanced, solid tumor malignancies who have pre-identified deleterious germline or somatic mutations in the homologous recombination deoxyribonucleic acid (DNA) repair pathway (HR deficient). The trial is designed to assess the efficacy and safety of niraparib plus carboplatin in patients with evidence of HRD. The primary endpoint will be identifying the recommended phase 2 dose (RP2D) and schedule of niraparib plus carboplatin, as well as establishing the anti-tumor efficacy of niraparib plus carboplatin as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

Eligibility Criteria

Adults with advanced solid tumors and specific mutations that affect DNA repair (HR deficiency) are eligible. They must have measurable disease, be in good physical condition, and have tried standard therapies without success or cannot tolerate them. Pregnant women, those with recent other cancers or severe medical issues, and anyone who has had prior treatment with PARP inhibitors are excluded.

Inclusion Criteria

Advanced, solid tumor malignancy amenable to biopsy and consent to 4 mandatory biopsies

ECOG performance status (PS) of 0 to 1

Received and failed or intolerant to standard first line therapies or documented refusal

Adequate hepatic, bone marrow, and renal function at enrollment

Patients PRE-identified with germline or tumor deleterious mutation in DNA damage repair genes through Next-generation DNA sequencing

You are 18 years old or older.

You are able to perform your daily activities without assistance or with only slight assistance.

If you have a gene mutation that is known to cause problems with DNA repair, and it has been confirmed by testing and medical literature, you may not be eligible. Variations that are not well understood will also not be eligible.

Somatic mutations PRE-identified through NGS in CLIA certified, CAP tested, and bioinformatics-validated testing lab

You have a specific genetic mutation that affects your body's ability to repair damaged DNA.

You have a type of cancer that can be examined with a biopsy, and you must agree to have four biopsies during the study.

You are able to swallow pills without crushing or breaking them.

Exclusion Criteria

Prior PARP inhibitor-based therapy

You have a digestive system disorder that affects how your body absorbs medication.

Prior disease progression while receiving platinum chemotherapy or platinum chemotherapy within the last 6 months

Active severe infection or known chronic infection with HIV or hepatitis B virus

Cardiovascular disease problems within the last 6 months or QT prolongation ≥ 481 milliseconds

Life-threatening visceral disease or severe concurrent disease causing unacceptable safety risks or compromising compliance

Radiotherapy encompassing >20% of the bone marrow

Known, persistent > Grade 2 toxicity from prior cancer therapy

Known history of myelodysplastic syndrome (MDS)

Participant Groups

The trial is testing the combination of niraparib plus carboplatin to find the safest and most effective dose for patients with HR-deficient tumors. It's a Phase I study where doses will gradually increase to determine how well participants' tumors respond according to RECIST v1.1 criteria.

1Treatment groups

Experimental Treatment

Group I: Niraparib and CarboplatinExperimental Treatment2 Interventions

Niraparib will be administered orally, once daily for 21 days of each 21-day cycle in escalating doses depending on cohort patient is assigned to. Carboplatin will be administered via an injection on Day 2 of a given 21-day cycle. The dose a patient receives will depend on which cohort the patient is assigned to.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Paraplatin for: