Overview

This trial is active, not recruiting.

Condition advanced cancers
Treatments talazoparib tosylate, phone call
Phase phase 2
Target PARP
Sponsor M.D. Anderson Cancer Center
Collaborator BioMarin Pharmaceutical
Start date December 2014
End date December 2019
Trial size 270 participants
Trial identifier NCT02286687, 2013-0961, NCI-2014-02494

Summary

The goal of this clinical research study is to learn if talazoparib can help to control advanced cancer in patients who have a specific type of alteration. The safety of this drug will also be studied.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants have mutation of BRCA1 or BRCA 2. Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
talazoparib tosylate BMN 673
Participants receive Talazoparib tosylate at 1 mg by mouth daily.
phone call
Study staff calls participant after completion of the treatment.
(Experimental)
Participants have deletion of BRCA1 or BRCA2. Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
talazoparib tosylate BMN 673
Participants receive Talazoparib tosylate at 1 mg by mouth daily.
phone call
Study staff calls participant after completion of the treatment.
(Experimental)
Participants have mutation or deletion in ATM, PALB2, MER11, RAD50, NBS1, ATR; amplification of EMSY or Fanconi Anemia Genes. Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
talazoparib tosylate BMN 673
Participants receive Talazoparib tosylate at 1 mg by mouth daily.
phone call
Study staff calls participant after completion of the treatment.
(Experimental)
Participants have mutation or deletion in PTEN, or PTEN Loss. Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
talazoparib tosylate BMN 673
Participants receive Talazoparib tosylate at 1 mg by mouth daily.
phone call
Study staff calls participant after completion of the treatment.
(Experimental)
Participants have Myriad HRD assay LOH >40% homologous recombination defects. Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
talazoparib tosylate BMN 673
Participants receive Talazoparib tosylate at 1 mg by mouth daily.
phone call
Study staff calls participant after completion of the treatment.
(Experimental)
Participants have Germline mutations of BRCA 1 or BRCA 2 (not breast or ovarian cancer) Participants receive Talazoparib tosylate at 1 mg by mouth daily. Study staff calls participant after completion of the treatment.
talazoparib tosylate BMN 673
Participants receive Talazoparib tosylate at 1 mg by mouth daily.
phone call
Study staff calls participant after completion of the treatment.

Primary Outcomes

Measure
Clinical Benefit of Talazoparib Tosylate
time frame: Every 8 weeks for 6 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Patients with advanced or metastatic cancer that is refractory to standard therapy or has relapsed after standard therapy. 2. Patients must have one of the following: somatic mutations or deletions in BRCA1 or BRCA2; genomic alterations in other BRCA pathway genes (subcohorts: a. ATM, b. PALB2, c. Fanconi Anemia genes, d. ARID1A, and e. other genes, e.g. MER11, RAD50, NBS1, ATR; amplification of EMSY); mutations or homozygous deletions in PTEN and/or PTEN loss by IHC; homologous recombination deficiency (Myriad HRD score >/=42; not breast or ovarian cancer); or germline mutation in BRCA1 or BRCA 2 (not breast or ovarian cancer) 3. Patients must be >/=18 years of age. 4. Patients must have measurable disease by RECIST 1.1. 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. 6. Adequate organ function as defined: absolute neutrophil count >/=1500/mL; platelets >/= 100,000/mL; hemoglobin >/= 9 g/dL (or >/=5.6mmol/L); serum creatinine /= 60 ml/min for patients with creatinine >1.5xULN); serum total bilirubin 1.5xULN); AST(SGOT) and ALT(SGPT) /=4 weeks beyond treatment with any chemotherapy or other investigational therapy to include hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation. 8. Women of child-bearing potential MUST have a negative serum or urine HCG test unless prior tubal ligation (>/= 1 year before screening), total hysterectomy or menopause (defined as 12 consecutive months of amenorrhea). Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use dual contraception for the duration of study participation and for 120 days after the last dose of talazoparib. 9. Ability to understand and willingness to sign informed consent form prior to initiation of the study and any study procedures 10. Patients need to have biopsiable disease to enroll on cohort 1-4. Patients eligible for Cohort 5 with a germline BRCA alteration can be enrolled even if they do not have biopsiable disease. Exclusion Criteria: 1. Patients who are pregnant or breastfeeding; 2. Prior treatment with a PARP inhibitor; 3. Known Hepatitis B, Hepatitis C or HIV infection; 4. Inability or unwillingness to swallow pills. 5. Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization. 6. Any medical condition or diagnosis that would likely impair absorption of an orally administered drug (e.g. gastrectomy, ileal bypass, chronic diarrhea, gastroparesis). 7. Inability to comply with the study and follow-up procedures. 8. History of CVA, myocardial infarction or unstable angina within the previous 6 months before starting therapy 9. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 10. Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial 11. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless or clinical stability.

Additional Information

Official title Phase II Study of the PARP Inhibitor BMN 673 (Talazoparib Tosylate) in Advanced Cancer Patients With Somatic Alterations in BRCA1/2, Mutations/Deletions in PTEN or PTEN Loss, a Homologous Recombination Defect, Mutations/Deletions in Other BRCA Pathway Genes and Germline Mutation in BRCA1/2 (Not Breast or Ovarian Cancer)
Principal investigator Sarina Piha-Paul, MD
Description Study Drug Administration: If you are found to be eligible to take part in this study, you will take talazoparib capsules by mouth 1 time each day. You should take the study drug at about the same time every day with or without food. If you miss a dose, you should skip that dose and take your next dose as scheduled. If you vomit after taking the study drug, do not take another dose to make it up. Wait and take your next dose as scheduled. Study Visits: Each study cycle is 28 days. During Weeks 1 and 2 of Cycle 1: - You will have a physical exam. - Blood (about 4 teaspoons) will be drawn for routine tests. - Blood (about 2 teaspoons) will be drawn for biomarker and genetic testing. - During Week 1, urine will be collected for routine tests. During Weeks 3 and 4 of Cycle 1: - You will have a physical exam. - Blood (about 4 teaspoons) will be drawn for routine tests. - Blood (about 2 teaspoons) will be drawn for biomarker and genetic testing. - During Week 3, depending on when you are enrolled, you will have a tumor biopsy for PD testing. The study doctor will discuss this with you. During Week 1 of Cycles 2 and beyond: - You will have a physical exam. - Blood (about 4 teaspoons) and urine will be drawn for routine tests. During Weeks 2, 3, and 4 of Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine tests. During Weeks 4 of Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for biomarker and genetic testing. Every 8 weeks for 6 months and then every 12 weeks after that, you will have a CT or MRI scan to check the status of the disease. If the disease appears to get better, you will have a repeat scan within 4 weeks. Length of Treatment: You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on this study will be over after 1 year of follow-up calls. End-of-Treatment Visit: Right after your last dose of study drug, you will have an end-of-treatment visit: - You will have a physical exam. - Blood (about 6 teaspoons) and urine will be drawn for routine tests and biomarker and DNA testing. Follow-Up Visit: About 30 days after your last dose of study drug: Blood (about 4 teaspoons) and urine will be collected for routine tests. Blood (about 2 teaspoons) will be drawn for and biomarker and DNA testing. Long Term Follow-Up: The study staff will call you to ask how you are doing every 12 weeks for up to 1 year. Each call should last about 5 minutes. This is an investigational study. Talazoparib is not FDA-approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work. Up to 270 participants will be enrolled in this study. All will take part at MD Anderson.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.
Location data was received from the National Cancer Institute and was last updated in July 2016.