Veliparib and Irinotecan Hydrochloride in Treating Patients With Cancer That Is Metastatic or Cannot Be Removed by Surgery
A Phase I Dose-Escalation Study of Oral ABT-888 (NSC #737664) Plus Intravenous Irinotecan (CPT-11, NSC#616348) Administered in Patients With Advanced Solid Tumors
12 other identifiers
interventional
73
1 country
5
Brief Summary
This phase I trial studies the side effects and best dose of veliparib when given together with irinotecan hydrochloride in treating patients with cancer that has spread to other parts of the body or that cannot be removed by surgery. Irinotecan hydrochloride can kill cancer cells by damaging the deoxyribonucleic acid (DNA) that is needed for cancer cell survival and growth. Veliparib may block proteins that repair the damaged DNA and may help irinotecan hydrochloride to kill more tumor cells. Giving irinotecan hydrochloride together with veliparib may kill more cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2008
Longer than P75 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 18, 2007
CompletedFirst Posted
Study publicly available on registry
December 19, 2007
CompletedStudy Start
First participant enrolled
March 18, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 16, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
January 16, 2020
CompletedApril 15, 2025
April 1, 2025
11.8 years
December 18, 2007
April 11, 2025
Conditions
Outcome Measures
Primary Outcomes (4)
Optimal biologic dose (OBD)
Defined as the dose level at which no greater inhibition of poly(ADP-ribose) (PAR) levels in tumor cells is identified, relative to the next lower dose.
Up to day 9 of course 1
Maximum administered dose of study drugs
Defined as the dose level at which at least 2 of 6 patients develop dose-limiting toxicity (DLT) as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Up to 21 days
Maximally tolerated dose (MTD) of study drugs
Defined as the dose at which no more than 1 patient of 6 develops DLT as graded by the NCI CTCAE version 5.0.
Up to 21 days
Recommended phase II dose (RP2D) of study drugs
Defined as the MTD if DLTs are observed before achieving the OBD, or the OBD if DLTs are not observed before reaching the OBD as graded by the NCI CTCAE version 5.0.
Up to 21 days
Secondary Outcomes (2)
Incidence of adverse events (AEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Up to 30 days
Tumor response
Up to 30 days
Other Outcomes (8)
Change in poly(ADP-ribose) polymerase (PARP) levels in peripheral blood mononuclear cells (PBMCs)
Baseline to up to 10 days
Pharmacokinetic (PK) profile of veliparib
Baseline and at days 1, 2, and 3 of course 1 and days 1, 8, 9, and 10 of course 2
Poly(ADP-ribose) (PAR) activity inhibition in peripheral blood mononuclear cells and tumor cells
Up to 10 days
- +5 more other outcomes
Study Arms (3)
Dose escalation (irinotecan hydrochloride and veliparib)
EXPERIMENTALPatients receive irinotecan hydrochloride IV over 90 minutes on days 1 and 8 and veliparib PO BID on days -1 to 14 (days 3-14 of course 1 only). Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Expansion portion (irinotecan hydrochloride and veliparib)
EXPERIMENTALPatients receive irinotecan hydrochloride IV over 90 minutes on days 1 and 8 and veliparib PO BID on days 1-15 (days 2-15 of course 1 only). Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intermittent dose escalation (irinotecan, ABT-888)
EXPERIMENTALPatients receive irinotecan hydrochloride IV over 90 minutes on days 3 and 10 and veliparib PO BID on days 1 to 4 and 8-11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Correlative studies
Correlative studies
Given PO
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed diagnosis of malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective or for whom CPT-11 treatment would be a viable therapy regimen; patients with solid hematologic malignancies (Hodgkin's and non-Hodgkin's lymphomas) may be included as long as a bone marrow has been performed within 6 weeks of treatment
- Patients enrolled on the expansion portion of the study will consist of two cohorts: those patients who are triple-negative, BRCA-mutant positive and those patients who have triple-negative, non-BRCA mutated breast cancer
- Patients enrolled on the dose escalation for intermittent ABT-888 portion of the study must histologically or cytologically confirmed diagnosis of malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective or for whom CPT-11 treatment would be a viable therapy regimen; patients with solid hematologic malignancies (Hodgkin's and non-Hodgkin's lymphomas) may be included as long as a bone marrow has been performed within 6 weeks of treatment
- Patient must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines
- Patients must have tumors determined to be easily accessible for biopsy (e.g. pleural-based lesions, peripheral lymph nodes, soft tissue metastases, large liver metastases, etc)
- Prior chemotherapy is allowed; patients must not have received chemotherapy for 4 weeks prior to the initiation of study treatment and must have full recovery from any acute effects of any prior chemotherapy; patients must not have had nitrosoureas or mitomycin C for 6 weeks prior to the initiation of study treatment
- Prior radiation therapy is allowed; patients must not have received minimal radiation therapy (=\< 5% of their total marrow volume) within 3 weeks prior to the initiation of study treatment; otherwise, patients must not have received radiation therapy (\> 5% of their total marrow volume) within 4 weeks prior to the initiation of study treatment; patients who have received prior radiation to 50% or more of their total marrow volume will be excluded
- Prior experimental (non-Food and Drug Administration \[FDA\] approved) therapies and immunotherapies are allowed; patients must not have received these therapies for 4 weeks prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy of greater than 12 weeks
- Absolute neutrophil count (ANC) \>= 1,500/mcL
- Platelets (PLT) \>= 100,000/mcL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN); if liver metastases are present, =\< 5 x ULN
- Bilirubin =\< 1.5 x ULN
- Creatinine =\< 1.5 x ULN OR calculated or measured creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine above institutional normal
- +3 more criteria
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients who have been administered ABT-888 as part of a single or limited dosing study, such as a phase 0 study, should not necessarily be excluded from participating in this study solely because of receiving prior ABT-888
- Patients may not have received any other investigational agents within 4 weeks of study entry
- History of allergic reactions attributed to the following:
- Camptothecin derivatives (e.g., topotecan \[topotecan hydrochloride\], irinotecan, or exatecan \[exatecan mesylate\])
- Any ingredients contained within the liquid irinotecan solution (e.g., sorbitol) or
- Any antiemetics or antidiarrheals appropriate for administration with study therapy (e.g., loperamide or dexamethasone)
- Patients must not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study except for medications that are prescribed for supportive care but may potentially have an anti-cancer effect (i.e. megestrol acetate, bisphosphonates); these medications must have been started 1 month prior to enrollment on this study; in addition, men receiving treatment for prostate cancer will be maintained at castrate levels of testosterone by continuation of luteinizing-releasing hormone agonists
- Patients with uncontrolled seizures
- Patients with known active brain metastases should be excluded from this clinical trial; patients with prior treated brain metastases are allowed, providing that they were not accompanied by seizures and that a baseline brain magnetic resonance imaging (MRI) scan prior to study entry demonstrates no current evidence of brain metastases; all patients with central nervous system (CNS) metastases must be stable for \> 3 months after treatment and off steroid treatment prior to study enrollment
- Any patient requiring chronic maintenance of white blood cell counts or granulocyte counts through the use of growth factor support (e.g. Neulasta, Neupogen)
- Any patient requiring cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) isoform-inducing drugs (e.g. phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, ketoconazole, St. John's wort) will be excluded; CYP3A4-inducing drugs should be discontinued at least 2 weeks prior to the first cycle of irinotecan
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
Yale University
New Haven, Connecticut, 06520, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Covenant Medical Center Harrison
Saginaw, Michigan, 48602, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Patricia M LoRusso
Yale University Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 18, 2007
First Posted
December 19, 2007
Study Start
March 18, 2008
Primary Completion
January 16, 2020
Study Completion
January 16, 2020
Last Updated
April 15, 2025
Record last verified: 2025-04