Testing the Combination of Anti-Cancer Drugs Talazoparib and Temozolomide in Patients With Advanced Stage Rare Cancers, RARE 2 Trial

NCT05142241 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: NCI-2021-1285800069210490
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests whether combination of talazoparib and temozolomide works to shrink tumors in patients with rare cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Talazoparib is an inhibitor of poly adenosine diphosphate-ribose polymerase (PARP), an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Temozolomide is in a class of medications called alkylating agents. It damages the cell's DNA and may kill cancer cells. Giving talazoparib in combination with temozolomide may help shrink advanced rare cancers or stop them from growing.

Conditions

Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Objective Response

  The number of participants with an objective response to treatment, defined as a complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Overall Response (OR) = CR + PR with CR indicating the disappearance of all target lesions and PR defined as a 30% or more decrease in the sum of the longest diameter of target lesions.

  Restaging scans were carried out every two cycles (8 weeks) until the end of treatment, an average of 3.3 months.

Other Outcomes (1)

• Estimated 6-month Progression-free Survival (PFS)

  At 6 months from treatment start date

Study Arms (1)

Treatment (talazoparib, temozolomide)

EXPERIMENTAL

Patients receive talazoparib PO QD on days 1-28 and temozolomide PO QD on days 2-6 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and may optionally undergo biopsy and/or blood sample collection at baseline and on the trial.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Talazoparib; Drug: Temozolomide

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (talazoparib, temozolomide)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (talazoparib, temozolomide)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (talazoparib, temozolomide)

Talazoparib DRUG

Given PO

Also known as: BMN 673, BMN-673, BMN673

Treatment (talazoparib, temozolomide)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temizole, Temodal, Temodar, Temomedac, TMZ

Treatment (talazoparib, temozolomide)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed rare solid tumors that have progressed on standard therapy or for whom there is no longer standard of care therapy. Other rare tumor types may be acceptable at the discretion of the principal investigator (PI)
• Patients must not be eligible for a higher priority study, such as a disease specific study of phase 2 or higher or a randomized study. Specifically, patients with pheochromocytoma and paraganglioma at the clinical center will be eligible for this study if they are not eligible for the NCT04394858 due to prior PARP inhibitor, dacarbazine (DTIC) or temozolomide therapy
• Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, with at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions)
• Patients consenting to biopsies must have a tumor site amenable to biopsy. If avoidable, the lesion for biopsy should not be selected as a target lesion for RECIST measurements
• Prior to entering the study, patients must have:
• \>= 3 weeks since completion of radiation therapy or major surgery
• \>= 5 half-lives or 3 weeks (whichever is shorter) since completion of biologic therapy or chemotherapy
• Should be at least 6 weeks out from nitrosoureas and mitomycin C
• \>= 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study
• \>= 1 week from palliative radiation therapy (patients on study may be eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy at the PI's discretion)
• Recovered to eligibility levels from prior toxicity or adverse events. Treatment with bisphosphonates is permitted
• Adults age \>= 18 years; children/adolescents age \>= 12 years to 17 years with body surface area (BSA) \>= 1.5 m\^2
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL

You may not qualify if:

• Sensory/motor neuropathy \>= grade 2
• Patients who are receiving any other investigational agents
• Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for \>= 1 month without requiring steroid and anti-seizure medication are eligible to participate
• History of allergic reactions attributed to compounds of similar chemical composition to study drugs
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
• Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible. For these patients, HBsAg and anti-HBc tests must be done within 28 days prior to enrollment
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). For these patients, an HCV RNA test must be done within 28 days prior to enrollment
• Uncontrolled intercurrent illness including, but not limited to, serious untreated infection, symptomatic respiratory failure/congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because temozolomide and talazoparib have demonstrated fetal harm in animal reproductive studies. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 1 months following the last dose of study drug

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Interventions

Biopsy; Specimen Handling; talazoparib; Temozolomide

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Alice P. Chen
• Organization: National Cancer Institute

chenali@mail.nih.gov

240-781-3274

Study Officials

• A P Chen

  National Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: December 1, 2021
• First Posted: December 2, 2021
• Study Start: July 11, 2022
• Primary Completion: September 26, 2025
• Study Completion: September 29, 2026
• Last Updated: September 1, 2026
• Results First Posted: August 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (2)