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

Running, not enrolling · Phase 2

Conditions studied: Adrenal Gland Pheochromocytoma, Hematopoietic and Lymphatic System Neoplasm, Malignant Solid Neoplasm, Paraganglioma

In brief

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.

Key facts

Study ID: NCT05142241
Run by: National Cancer Institute (NCI)
People needed: 14
Starts: 2022-07-11
Expected to finish: 2026-09-29
Last updated by the study team: 2025-11-18

Who can join

Age: 12 and older. Sex: any. Healthy volunteers: not accepted.

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
Hemoglobin >= 8 g/dL
Total bilirubin =< 1.5 X institutional upper limit of normal (=< 3 x upper limit of normal in the presence of documented Gilbert's syndrome or liver metastases at baseline)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X upper limit of normal (ULN)
Creatinine clearance >= 60 mL/min/1.73 m\^2 OR creatinine for adult patients: =< 1.5 X institutional ULN, for pediatric patients (< 18 years of age):
2 to < 6 years (0.8 mg/dL male, 0.8 mg/dL female)
6 to < 10 years (1 mg/dL male, 1 mg/dL female)
10 to < 13 years (1.2 mg/dL male, 1.2 mg/dL female)
13 to < 16 years (1.5 mg/dL male, 1.4 mg/dL female)
16 to < 18 years (1.7 mg/dL male, 1.4 mg/dL female)
Talazoparib and temozolomide can cause fetal harm based on animal reproductive and genetic toxicity studies. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 7 months after dosing with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of study drug administration. Women of child-bearing potential must have a negative pregnancy test (urine or serum) in the 8 days prior to beginning treatment, and again on cycle 1 day 1 of treatment

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

Where it is running

National Cancer Institute Developmental Therapeutics Clinic — Bethesda, Maryland, United States
National Institutes of Health Clinical Center — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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