Veliparib, ATR Kinase Inhibitor M6620, and Cisplatin in Treating Patients with Refractory Solid Tumors

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 >= 3 weeks (or >= 5 half-lives, whichever is shorter) prior to entering the study; patients must be >= 2 weeks since any prior administration of a study drug in an exploratory investigational new drug (IND)/phase 0 study and >= 1 week since any palliative radiation therapy; patients must have recovered to eligibility levels from prior toxicity or adverse events
• Age >= 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy > 3 months
• Absolute neutrophil count >= 1,500/mcL
• Hemoglobin >= 10 g/dL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 1.5 X institutional upper limit of normal (or =< 3 X upper limit of normal [ULN] in the setting of liver metastases)
• Creatinine =< 1.5 X institutional upper limit of normal or creatinine clearance >= 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 child-bearing 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 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 >= 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 >= 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 syndrome (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