Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin in People With Refractory Solid Tumors
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|ClinicalTrials.gov Identifier: NCT02723864|
Recruitment Status : Recruiting
First Posted : March 31, 2016
Last Update Posted : August 1, 2018
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 VX-970. They want to test if this drug combination slows the growth of cancer and is safe.
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.
People ages 18 and older with:
- Solid tumors that have progressed after treatment or for which no treatment exists
- Normal organ and marrow function
Participants will be screened with:
- Medical history
- Physical exam
- CT scan or 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.
|Condition or disease||Intervention/treatment||Phase|
|Neoplasms||Drug: Veliparib + VX-970 + Cisplatin||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin in Patients With Refractory Solid Tumors|
|Study Start Date :||March 23, 2016|
|Estimated Primary Completion Date :||December 31, 2018|
|Estimated Study Completion Date :||December 31, 2019|
VX-970 will be administered IV on Days 2 and 9 of each 21-day cycle; Veliparib will be administered orally twice a day (BID) Days 1-3 and 8-10 of each cycle; Cisplatin will be administered at 40 mg/m2 IV Day 1 (and Day 8 from DL3 onwards) of each cycle
Drug: Veliparib + VX-970 + Cisplatin
ATR protein kinase is central to the DNA damage response and homologous recombination, activating a series of phosphorylation cascades, culminating in cell cycle arrest to allow time for DNA repair. PARP plays a pivotal role in base-excision repair of single strand breaks formed either due to direct genotoxic stress or during the processing of double strand breaks. Preclinical studies show ATR inhibitor VX-970 synergizes with cisplatin to induce DNA damage and antitumor activity. The addition of PARP inhibitor veliparib with VX-970 allows for impairment of DNA repair, induction of a BRCA null phenotype, and potentiation of the antitumor activity of cisplatin.
- To establish the safety, tolerability, and MTD of the combination of VX 970 and veliparib in combination with cisplatin in patients with advanced refractory solid tumors [ Time Frame: Cycle 1 ]Adverse event descriptions and grading scales from the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting.
- To assess the effect of the combination of VX-970, veliparib, and cisplatin on markers of DNA damage and apoptosis [ Time Frame: Cycles 1 and 2 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02723864
|Contact: Ashley B Bruns||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|United States, Massachusetts|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02115|
|United States, Texas|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030-4096|
|Principal Investigator:||Alice P Chen, M.D.||National Cancer Institute (NCI)|