Status:
COMPLETED
Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin in People With Refractory Solid Tumors
Lead Sponsor:
National Cancer Institute (NCI)
Conditions:
Neoplasms
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
Background: The drug cisplatin treats certain cancers when given with other chemotherapy drugs. Researchers think combining cisplatin with 2 other drugs could block proteins that support cancer cell ...
Detailed Description
Background: * Ataxia-telangiectasia-related (ATR) protein kinase is central to the deoxyribonucleic acid (DNA) damage response and homologous recombination, activating a series of phosphorylation cas...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA:
- Patients must have histologically confirmed solid tumors for which standard therapy known to prolong survival has failed in the metastatic setting or for which standard therapies do not exist.
- Tumor amenable to biopsy and willingness to undergo tumor biopsies before and after M6620 (VX-970) treatment during the expansion phase of the trial (biopsies optional during the escalation phase).
- Patients must have completed any chemotherapy, radiation therapy, surgery, or biologic therapy greater than or equal to 3 weeks (or greater than or equal to 5 half-lives, whichever is shorter) prior to entering the study. Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in an exploratory investigational new drug (IND)/Phase 0 study and greater than or equal to 1 week since any palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events.
- Age greater than or equal to 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
- Life expectancy \> 3 months.
- Patients must have normal organ and marrow function as defined below:
- absolute neutrophil count greater than or equal to 1,500/mcL
- hemoglobin greater than or equal to 10 g/dL
- platelets greater than or equal to 100,000/mcL
- total bilirubin less than or equal to 1.5 X institutional upper limit of normal
- Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase(SGOT)/alanine aminotransferase (ALT) Serum glutamic pyruvic transaminase (SGPT) less than or equal to 1.5 X institutional upper limit of normal (OR \< 3X upper limit of normal (ULN) in the setting of liver metastases)
- creatinine less than or equal to 1.5X institutional upper limit of normal
- OR
- creatinine clearance greater than or equal to 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- The effects of M6620 (VX-970) and veliparib on the developing human fetus are unknown. For this reason and because cisplatin is known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after completing study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after completion of administration of study agents.
- Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with M6620 (VX-970). In addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy.
- Patients must be able to swallow whole tablets or capsules. Nasogastric or gastric (G)-tube administration is not allowed. Any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed.
- Ability to understand and the willingness to sign a written informed consent document.
- During the expansion phase of the protocol, patients must have disease amenable to biopsy and be willing to undergo pre- and post-treatment biopsies.
- Patients must have greater than or equal to 10.0 g/dL hemoglobin (Hb) and no blood transfusion in the past 28 days to receive Veliparib.
- EXCLUSION CRITERIA:
- Patients who are receiving any other investigational agents.
- Patients with known active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients whose brain metastatic disease status has remained stable for greater than or equal to 4 weeks following treatment of brain metastases are eligible to participate at the discretion of the principal investigator.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active untreated infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients required to be on any of the concomitant medications are excluded.
- Pregnant women and women who are breastfeeding are excluded from this study because the effects of the study drugs on the developing fetus are unknown.
- Patients who have had prior platinum-based therapy who have \> Grade 1 neurotoxicity or ototoxicity at the time of enrollment will not be permitted on study.
- Patients with a seizure history will not be permitted on protocol due to association of veliparib with seizure activity in animal toxicology studies at higher doses. Patients on anticonvulsant medications will not be permitted on study due to the potential to lower plasma levels of anticonvulsants and risk for seizure activity.
- Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/Myelodysplastic syndromes (MDS), or with features suggestive of AML/MDS, or who have had prior allogeneic bone marrow transplant or double umbilical cord blood transplantation, should not receive Veliparib due to reports of MDS and leukemia secondary to oncology therapy on Cancer Therapy Evaluation Program (CTEP)-sponsored studies utilizing Veliparib.
- INCLUSION of WOMEN and MINORITIES
- Both men and women of all races and ethnic groups are eligible for this trial.
Exclusion
Key Trial Info
Start Date :
August 9 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 31 2021
Estimated Enrollment :
53 Patients enrolled
Trial Details
Trial ID
NCT02723864
Start Date
August 9 2017
End Date
December 31 2021
Last Update
February 8 2022
Active Locations (3)
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1
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
2
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
3
MD Anderson Cancer Center
Houston, Texas, United States, 77030-4096