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.
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)
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
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).
Parallel
Axitinib
DrugGiven PO
Crizotinib
DrugGiven PO
Palbociclib Isethionate
DrugGiven PO
Talazoparib Tosylate
DrugGiven PO
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.
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.
Plasma pharmacokinetic (PK) parameters (maximum plasma concentration)
Plasma pharmacokinetic parameters including the maximum plasma concentration. Descriptive statistics will be provided for these PK parameters in tabular form (n, mean, SD, CV, median, minimum, maximum, geometric mean and its associated CV) by trial arm, dose, cycle and day. Individual curves of serum concentration of each study drug versus time will be presented on log- and linear scale for all patients in the PK population. Furthermore, maximum and trough serum concentrations for the period from first dose to end of treatment will be presented on linear scale individual plots.
Plasma pharmacokinetic (PK) parameters (time to maximum plasma concentration)
Plasma pharmacokinetic parameters including the time to maximum plasma concentration Descriptive statistics will be provided for these PK parameters in tabular form (n, mean, SD, CV, median, minimum, maximum, geometric mean and its associated CV) by trial arm, dose, cycle and day. Individual curves of serum concentration of each study drug versus time will be presented on log- and linear scale for all patients in the PK population. Furthermore, maximum and trough serum concentrations for the period from first dose to end of treatment will be presented on linear scale individual plots.
Plasma pharmacokinetic (PK) parameters (area under the plasma concentration)
Plasma pharmacokinetic parameters including the area under the plasma concentration versus time curve will be estimated using non-compartmental analysis. Descriptive statistics will be provided for these PK parameters in tabular form (n, mean, SD, CV, median, minimum, maximum, geometric mean and its associated CV) by trial arm, dose, cycle and day. Individual curves of serum concentration of each study drug versus time will be presented on log- and linear scale for all patients in the PK population. Furthermore, maximum and trough serum concentrations for the period from first dose to end of treatment will be presented on linear scale individual plots.
Plasma pharmacokinetic parameters (Ctrough)
Plasma pharmacokinetic parameters including the Ctrough. Descriptive statistics will be provided for these PK parameters in tabular form (n, mean, SD, CV, median, minimum, maximum, geometric mean and its associated CV) by trial arm, dose, cycle and day. Individual curves of serum concentration of each study drug versus time will be presented on log- and linear scale for all patients in the PK population. Trough serum concentrations for the period from first dose to end of treatment will be presented on linear scale individual plots.
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M.D. Anderson Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
