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

NCT04693468 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2020-0436NCI-2020-06041
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm; Recurrent Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Incidence and severity of adverse events and serious adverse events in patients being treated with the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C). Severity of adverse events (AEs) will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Tabulations will be produced for safety parameters.

  Up to 30 days after the last investigational product administration

• Incidence of dose limiting toxicities

  Incidence of dose limiting toxicities of the combination of talazoparib with palbociclib (Arm A), axitinib (Arm B), and crizotinib (Arm C) will be assessed. Severity of AEs will be graded according to the NCI CTCAE version 5.0.

  Up to 30 days after the last investigational product administration

Secondary Outcomes (10)

• Plasma pharmacokinetic (PK) parameters (maximum plasma concentration)

  Up to 2 years

• Plasma pharmacokinetic (PK) parameters (time to maximum plasma concentration)

  Up to 2 years

• Plasma pharmacokinetic (PK) parameters (area under the plasma concentration)

  Up to 2 years

• Plasma pharmacokinetic parameters (Ctrough)

  Up to 2 years

• Plasma pharmacokinetic parameters (maximum)

  Up to 2 years

Study Arms (3)

Arm I (talazoparib, palbociclib)

EXPERIMENTAL

Patients receive talazoparib PO 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.

Drug: Palbociclib Isethionate; Drug: Talazoparib Tosylate

Arm II (talazoparib, axitinib)

EXPERIMENTAL

Patients receive talazoparib PO QD on days 1-28 and axitinib 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.

Drug: Axitinib; Drug: Talazoparib Tosylate

Arm III (talazoparib, crizotinib)

EXPERIMENTAL

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.

Drug: Crizotinib; Drug: Talazoparib Tosylate

Interventions

Axitinib DRUG

Given PO

Also known as: AG-013736, AG013736, Inlyta

Arm II (talazoparib, axitinib)

Crizotinib DRUG

Given PO

Also known as: MET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, Xalkori

Arm III (talazoparib, crizotinib)

Palbociclib Isethionate DRUG

Given PO

Also known as: PD 0332991-0054, PF-00080665-73

Arm I (talazoparib, palbociclib)

Talazoparib Tosylate DRUG

Given PO

Also known as: Talzenna

Arm I (talazoparib, palbociclib); Arm II (talazoparib, axitinib); Arm III (talazoparib, crizotinib)

Eligibility Criteria

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

You may qualify if:

• Pathogenic or likely pathogenic germline or somatic gene defect as determined by local assessment and classification in at least one of the following:
• Defect in DNA Damage Response (DDR) genes specified below for each cohort or other related genes at the discretion of the principal investigator in consultation with the MD Anderson Cancer Center Institute for Personalized Cancer Therapy Precision Oncology Decision Support (PODS) group. See below for additional eligibility guidance for Arms A - C:
• Eligibility for Arm A (Talazoparib + Palbociclib):
• Solid tumors with defects in DDR genes such as: BRCA1/2, PALB2, RAD51C/D, or other related genes at the discretion of the principal investigator, or
• MYC-aberrant solid tumors (e.g. overexpression, amplification, mutation)
• Eligibility for Arm B (Talazoparib + Axitinib):
• Solid tumors with defects in DDR genes such as: BRCA1/2, PALB2, RAD51C/D, or other related genes at the discretion of the principal investigator, or
• Participants with BRCA1/2 wild-type high-grade serous ovarian cancer, or
• Participants with metastatic castration-resistant prostate cancer without a specific and/or selected mutation
• Eligibility for Arm C (Talazoparib + Crizotinib):
• Solid tumors with defects in DDR genes such as: BRCA1/2, PALB2,36 RAD51C/D, or other related genes at the discretion of the principal investigator, or
• Solid tumors with defects in MET, ALK or ROS1 (e.g. MET mutations or amplifications, high MET expression, ALK translocations, ROS1 translocations) NOTE: Participants who are eligible for more than one Arm will be assigned according to physician preference.
• Histological or cytological diagnosis of a solid tumor that is advanced/metastatic, intolerable to standard therapy, resistant to effective standard therapy, or for which no standard therapy is available.
• Availability of a fresh or recent tumor tissue sample from a diagnostic biopsy/surgery or a metastatic tumor biopsy; the sample must have been obtained within 12 months prior to study enrollment. When only bone disease is present, an archival tumor tissue sample obtained within 5 years prior to study enrollment may be accepted for non-prostate cancer patients and a fresh bone biopsy may be accepted for prostate cancer patients only.
• NOTE: A fresh biopsy should be encouraged for all participants at time of enrollment even if a previous biopsy is available. Optional on-treatment and at-progression biopsies will be encouraged for all participants. With agreement of the PI, if the archived tissue is not available and/ or it is unsafe to obtain a fresh biopsy at screening, the participant is eligible.

You may not qualify if:

• Prior anti-cancer therapy within 2 weeks prior to study enrollment or prior radiation therapy within 2 weeks prior to study enrollment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed at least 2 days prior to study enrollment and no clinically significant toxicities are expected (e.g. mucositis, esophagitis).
• Major surgery within 4 weeks prior to study enrollment.
• Participants with known hypersensitivity to either talazoparib or the additional study drug to be received per treatment arm: palbociclib (Arm A), axitinib (Arm B), crizotinib (Arm C).
• Diagnosis of myelodysplastic syndrome (MDS).
• Known symptomatic brain metastases requiring steroids. Participants with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 2 weeks, and are neurologically stable. Of note, participants who required a single dose of corticosteroids on days receiving radiation treatment do not require a 2-week washout.
• Persisting toxicity related to prior therapy (NCI CTCAE v5.0 Grade \> 1). However, alopecia and sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 adverse events not constituting a safety risk, based on the investigators judgement, are acceptable.
• Active infection requiring systemic therapy. Minor infections, e.g. periodontal infection or urinary tract infection (UTI), which may be treated with short term oral antibiotics are allowed.
• Participants with known uncontrolled HIV virus or Acquired immunodeficiency syndrome. Note: Patients with history of controlled HIV virus will be considered eligible for this trial.
• Participants with uncontrolled Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening. Note: Participants with controlled hepatitis B or hepatitis C will be considered eligible for this trial.
• Clinically significant cardiovascular disease, including any of the following:
• Myocardial infarction or symptomatic cardiac ischemia within 6 months before screening;
• Congestive heart failure New York Heart Association class III or IV;
• History of clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes) within 1 year before screening;
• History of Mobitz II second degree or third degree heart block unless a permanent pacemaker is in place;
• Hypotension as indicated by systolic blood pressure \<86 mm Hg at screening;

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MDAndersonCancerCenterWebsite

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Axitinib; Crizotinib; talazoparib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperidines; Aminopyridines; Pyridines

Study Officials

• Timothy A Yap

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy A. Yap

CONTACT

713-563-1784; tyap@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2020
• First Posted: January 5, 2021
• Study Start: December 1, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (1)