Talazoparib + Temozolomide for Prostate Cancer

Not currently recruiting at 10 trial locations

Overseen By Karen Autio, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: GnRH analogs

Must not be taking: Taxanes, PARP inhibitors

Disqualifiers: Brain metastasis, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of two drugs, talazoparib (Talzenna) and temozolomide, for men with a specific type of advanced prostate cancer that has spread and resists hormone therapy. The goal is to determine the safest dose and assess the treatment's effectiveness against cancer. Men with confirmed prostate cancer unresponsive to past treatments, particularly those without certain genetic mutations, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial protocol does not clearly specify if you must stop taking your current medications. However, you cannot use certain medications that might interact with the trial drugs within 14 days before starting the trial. It's best to discuss your current medications with the trial team to see if any need to be paused or adjusted.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is testing the combination of talazoparib and temozolomide to determine the safest dose for prostate cancer patients. Previous studies identified common side effects, including low blood cell counts—such as low platelets, white blood cells, and red blood cells—and fatigue. Higher doses of talazoparib have been linked to more severe effects, particularly on blood cell counts. As this combination remains under study, ongoing trials are crucial for gaining a better understanding of its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Talazoparib and Temozolomide for treating metastatic castration-resistant prostate cancer because this combination offers a unique approach to tackling cancer cells. Unlike standard treatments that mainly focus on hormonal therapies like androgen deprivation therapy, Talazoparib is a PARP inhibitor, which targets cancer cells' ability to repair their DNA, making them more vulnerable to damage. Temozolomide, a chemotherapy drug, further enhances this effect by damaging the DNA of cancer cells, potentially leading to better outcomes. This combo could offer a new hope for patients who don't have mutations in DNA damage repair genes, targeting the cancer in a way that existing treatments might not.

What evidence suggests that talazoparib and temozolomide might be an effective treatment for prostate cancer?

Research has shown that the drugs talazoparib and temozolomide may help treat advanced prostate cancer that doesn't respond to hormone therapy. One study found that about 30.8% of patients experienced a positive response, with significant reductions in cancer cell numbers. In this trial, participants with metastatic castration-resistant prostate cancer will receive talazoparib and temozolomide. The drugs were tested at specific doses—1 mg of talazoparib and 75 mg/m² of temozolomide—which proved to be the most effective and safe. However, the study ended early due to safety concerns related to blood side effects. While these results are encouraging, more research is needed to fully understand the treatment's effectiveness and safety. ^{1 2 3 6 7}

Who Is on the Research Team?

Karen Autio, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to castration and has progressed after hormone therapy can join. They need a PSA increase, metastatic disease confirmed by scans, and good organ function. No recent radiation or certain drugs, no genetic mutations in specific DNA repair genes, and no other cancers within the last two years.

Inclusion Criteria

Bilirubin: </= 1.5 ULN (unless documented Gilbert's disease)

Your prostate cancer has been getting worse, as shown by certain tests.

My prostate cancer was confirmed by a lab test.

Exclusion Criteria

I have previously been treated with specific chemotherapy drugs.

I have brain metastasis or active leptomeningeal disease.

I have had radiation therapy within the last 3 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ib Treatment

Participants receive talazoparib and temozolomide to determine the safest dose

Duration not specified

Phase II Treatment

Participants receive talazoparib and temozolomide at the maximum tolerated dose to test efficacy

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Talazoparib
• Temozolomide

Trial Overview The trial is testing Talazoparib combined with Temozolomide for safety at the highest dose without severe side effects (1mg Talazoparib & 75mg/m² Temozolomide). Phase II checks how well this combo works against advanced prostate cancer that doesn't respond to hormone therapy.

How Is the Trial Designed?

Group I: Metastatic Castration Resistant Prostate Cancer Experimental Treatment 2 Interventions

Participants have Metastatic Castration Resistant Prostate Cancer and No Mutations in DNA Damage Repair

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

Approved in United States as Talzenna for:

• Deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer

Approved in European Union as Talzenna for:

• Monotherapy for the treatment of adult patients with germline BRCA1/2 mutations, who have HER2-negative locally advanced or metastatic breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e17036

A phase Ib/II study of intermittent talazoparib plus ... The identified RP2D was talazoparib 1 mg (D1-6) and temozolomide 75mg/m2 (D2-8). 4 (30.8%) patients met the efficacy endpoint (3 CTC responses, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04019327

A Study of the Drugs Talazoparib and Temozolomide in ... The purpose of this study is to determine what the safest dose of talazoparib plus temozolomide for participants with metastatic castration resistant ...

3. link.springer.com link.springer.com/article/10.1007/s10637-025-01580-1

A phase 1b/2 study of intermittent talazoparib plus ... The phase 2 portion was terminated early. Across dose levels, three (18.8%) patients met the efficacy endpoint. Hematologic toxicity was dose- ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40906325/

A phase 1b/2 study of intermittent talazoparib plus ... The phase 2 portion was terminated early. Across dose levels, three (18.8%) patients met the efficacy endpoint. Hematologic toxicity was dose- ...

5. researchgate.net researchgate.net/publication/395269717_A_phase_1b2_study_of_intermittent_talazoparib_plus_temozolomide_in_patients_with_metastatic_castration-resistant_prostate_cancer_and_no_mutations_in_DNA_damage_response_genes

(PDF) A phase 1b/2 study of intermittent talazoparib plus ... Across dose levels, three (18.8%) patients met the efficacy endpoint. Hematologic toxicity was dose-limiting in this combination strategy using ...

6. researchgate.net researchgate.net/publication/393499675_Exposure-Safety_Analyses_of_Talazoparib_in_Combination_with_Enzalutamide_in_Patients_with_Metastatic_Castration-Resistant_Prostate_Cancer_mCRPC_in_the_TALAPRO-2_Trial

(PDF) Exposure-Safety Analyses of Talazoparib in ... The results indicated that higher talazoparib exposure, C avg,t , was associated with a higher risk of Grade ≥ 3 anemia, thrombocytopenia, and neutropenia.

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04019327/

Clinical Trial: NCT04019327 The purpose of this study is to determine what the safest dose of talazoparib plus temozolomide for participants with metastatic castration resistant prostate ...