Phase 1
Completed N=53
Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin in People With Refractory Solid Tumors
Neoplasms
Source: ClinicalTrials.gov NCT02723864 ↗
Enrolled (actual)
53
Serious AEs
35.9%
Results posted
Jan 2022
Primary outcomePrimary: Number of Participants With Worst Grade 2 or Higher Adverse Events Occurring in >5% of Participants at Least Possibly Related to Study Drugs — 1; 0; 0; 0 Participants
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 growth. The other drugs are ABT-888 (veliparib) and M6620 (VX-970). They want to test if this drug combination slows the growth of cancer and is safe.
Objectives:
To test the safety and tolerability of VX-970 and veliparib combined with cisplatin in people with advanced refractory solid tumors. To determine the maximum tolerated dose of these drugs.
Eligibility:
People ages 18 and older with:
* Solid tumors that have progressed after treatment or for which no treatment exists
* Normal organ and marrow function
Design:
Participants will be screened with:
* Medical history
* Physical exam
* Computed tomography (CT) scan or magnetic resonance imaging (MRI)
* Blood and urine tests
Participants will get the study drugs in 3-week cycles:
* Cisplatin in a vein on 1 or 2 days
* VX-970 in a vein on 2 days
* Veliparib by mouth twice a day on 6 days
In each cycle, participants will have 5 physical exams and blood tests 5 times.
In some cycles, participants will have CT scans or MRIs.
In cycle 1, participants may have 2 tumor biopsies. A small piece of tissue is removed by needle.
Participants will keep a study diary. They will write when they take the drugs and if they have side effects.
Participants will stay in the study as long as they tolerate the drugs and their tumors are not getting worse.
Participants will have a phone call about a month after their last dose.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Worst Grade 2 or Higher Adverse Events Occurring in >5% of Participants at Least Possibly Related to Study Drugs |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With RAD51 Recombinase (Rad51), Phosphorylated Histone H2AX (γH2AX), Phosphorylated at Serine 343 (pS343)-Nibrin (Nbs1), and Phosphorylated KRAB-associated Protein 1 (pKAP-1) Induced After Treatment |
5; 5; 0; 0; 1; 0 | — |
| SECONDARY Number of Participants With a Best Response to the Antitumor Activity of Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
- 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 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.
Data sourced from ClinicalTrials.gov (NCT02723864). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.