Talazoparib in Treating Patients with Recurrent, Locally Advanced or Metastatic Tumors and Alterations in the BRCA or PTEN Genes
This trial is active, not recruiting.
|Treatments||talazoparib tosylate, phone call|
|Sponsor||M.D. Anderson Cancer Center|
|Start date||December 2014|
|End date||December 2019|
|Trial size||270 participants|
|Trial identifier||NCT02286687, 2013-0961, NCI-2014-02494|
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.
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Clinical Benefit of Talazoparib Tosylate
time frame: Every 8 weeks for 6 months
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 = 1.5 X ULN (or GFR >/= 60 ml/min for patients with creatinine >1.5xULN); serum total bilirubin = 1.5 X ULN (direct bilirubin =ULN if total bili > 1.5xULN); AST(SGOT) and ALT(SGPT) = 2.5X ULN (or =5xULN if liver mets); INR or PT =1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; aPTT =1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 7. Patients must be >/=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.
|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.|
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