Talazoparib and Palbociclib, Axitinib, or Crizotinib for the Treatment of Advanced or Metastatic Solid Tumors, TalaCom Trial

Advanced Malignant Solid Neoplasm Clinical Trial

Official title: Modular Phase 1B Hypothesis-Testing, Biomarker-Driven, Talazoparib Combination Trial (TalaCom)

Status Recruiting

Clinical Trial Summary

This phase Ib trial is to find out the best dose, possible benefits and/or side effects of talazoparib when given in combination with palbociclib, axitinib, or crizotinib in treating patients with solid tumors that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). PARPs are proteins that help repair damaged DNA, the genetic material that serves as the body's instruction book. PARP inhibitors, such as talazoparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Palbociclib, axitinib, and crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving talazoparib in combination with palbociclib, axitinib, or crizotinib may help control locally advanced or metastatic solid tumors.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability, and establish the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of the combination of talazoparib tosylate (talazoparib) with palbociclib isethionate (palbociclib) (Arm A), axitinib (Arm B), and crizotinib (Arm C) in patients with advanced solid tumors.

II. To assess the safety and toxicity profile of the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C).

SECONDARY OBJECTIVES:

I. To evaluate the pharmacokinetic and pharmacodynamic profile of the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C).

II. To obtain a preliminary assessment of the antitumor activity of the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C).

III. To assess predictive biomarkers of response and resistance to the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C).

OUTLINE: This is a phase I, dose-escalation study. Patients are assigned to 1 of 3 arms.

ARM A: Patients receive talazoparib orally (PO) once daily (QD) on days 1-21 or 1-28 and palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.

ARM B: Patients receive talazoparib PO QD on days 1-28 and axitinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.

ARM C: Patients receive talazoparib PO QD on days 1-28 and crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.

After the completion of study treatment, patients are followed up for 90 days and then every 12 weeks until progression of disease, receipt of another cancer drug, or for another two years. ;

Related Conditions & MeSH terms

• Advanced Malignant Solid Neoplasm
• Metastatic Malignant Solid Neoplasm
• Neoplasms
• Recurrent Malignant Solid Neoplasm

• NCT number: NCT04693468
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Timothy A. Yap
• Phone: 713-563-1784
• Email: tyap@mdanderson.org
• Status: Recruiting
• Phase: Phase 1
• Start date: December 1, 2020
• Completion date: September 3, 2025