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Veliparib and Irinotecan Hydrochloride in Treating Patients With Cancer That Is Metastatic or Cannot Be Removed by Surgery

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00576654
First received: December 18, 2007
Last updated: June 23, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Advanced Malignant Solid Neoplasm Breast Carcinoma Colon Carcinoma Deleterious BRCA1 Gene Mutation Estrogen Receptor Negative HER2/Neu Negative Hodgkin Lymphoma Lung Carcinoma Metastatic Malignant Neoplasm Metastatic Malignant Solid Neoplasm Non-Hodgkin Lymphoma Ovarian Carcinoma Pancreatic Carcinoma Progesterone Receptor Negative Stage III Breast Cancer Stage III Colon Cancer Stage III Lung Cancer Stage III Ovarian Cancer Stage III Pancreatic Cancer Stage IIIA Breast Cancer Stage IIIA Colon Cancer Stage IIIA Ovarian Cancer Stage IIIB Breast Cancer Stage IIIB Colon Cancer Stage IIIB Ovarian Cancer Stage IIIC Breast Cancer Stage IIIC Colon Cancer Stage IIIC Ovarian Cancer Stage IV Breast Cancer Stage IV Colon Cancer Stage IV Lung Cancer Stage IV Ovarian Cancer Stage IV Pancreatic Cancer Stage IVA Colon Cancer Stage IVB Colon Cancer Triple-Negative Breast Carcinoma Unresectable Malignant Neoplasm Unresectable Solid Neoplasm Drug: Irinotecan Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Veliparib Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 4.0 [ Time Frame: Up to 21 days ]
  • 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 4.0 [ Time Frame: Up to 21 days ]
  • OBD defined as the dose level at which no greater inhibition of PAR levels in tumor cells is identified, relative to the next lower dose [ Time Frame: Up to day 9 of course 1 ]
  • 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 4.0 [ Time Frame: Up to 21 days ]

Secondary Outcome Measures:
  • Incidence of AEs, graded using the NCI CTCAE version 4.0 [ Time Frame: Up to 30 days ]
    Described by point estimates and exact 90% confidence intervals.

  • Tumor response, evaluated using RECIST version 1.1 [ Time Frame: Up to 30 days ]

Other Outcome Measures:
  • Change in gamma-H2AX foci and/or Rad51 levels [ Time Frame: Baseline to up to day 9 of course 1 ]
    Summarized with standard descriptive statistics (N, median, mean, standard deviation, minimum, maximum, and 90% confidence interval for the mean).

  • Change in PARP levels in PBMCs [ Time Frame: Baseline to up to 10 days ]
    Summarized with standard descriptive statistics (N, median, mean, standard deviation, minimum, maximum, and 90% confidence interval for the mean).

  • CTC counts [ Time Frame: Up to day 15 ]
  • ERCC1 expression levels [ Time Frame: Up to day 8 ]
  • PAR activity inhibition in peripheral blood mononuclear cells and tumor cells [ Time Frame: Up to 10 days ]
  • PD parameters [ Time Frame: 1 ]
    Will be summarized descriptively, by dose level and overall and will be summarized with standard statistics (N, median, mean, standard deviation, minimum, maximum, and 90% confidence interval for the mean).

  • PK parameters of irinotecan hydrochloride [ Time Frame: Baseline, 5.5 hours after infusion, and 28 hours after infusion of day one of course 1 ]
    Will be summarized descriptively within each cytochrome p450, family 2, subfamily C, polypeptide 9 (CYP2C9) polymorphism category, by dose level and overall.

  • PK profile of veliparib [ Time Frame: Baseline and at days 1, 2, and 3 of course 1 and days 1, 8, 9, and 10 of course 2 ]
    Summarized with standard descriptive statistics (N, median, mean, standard deviation, minimum, maximum, and 90% confidence interval for the mean).


Estimated Enrollment: 48
Actual Study Start Date: December 5, 2007
Estimated Primary Completion Date: August 1, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose escalation (irinotecan hydrochloride and veliparib)
Patients 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.
Drug: Irinotecan Hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • Camptothecin 11
  • Camptothecin-11
  • CPT 11
  • CPT-11
  • Irinomedac
  • U-101440E
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888
Experimental: Expansion portion (irinotecan hydrochloride and veliparib)
Patients 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.
Drug: Irinotecan Hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • Camptothecin 11
  • Camptothecin-11
  • CPT 11
  • CPT-11
  • Irinomedac
  • U-101440E
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888
Experimental: Intermittent dose escalation (irinotecan, ABT-888)
Patients 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.
Drug: Irinotecan Hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • Camptothecin 11
  • Camptothecin-11
  • CPT 11
  • CPT-11
  • Irinomedac
  • U-101440E
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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; once the recommended phase 2 dose is determined, additional patients will be enrolled who MUST have a deleterious mutation in BRCA and have human epidermal growth factor receptor 2 (Her-2) negative, estrogen receptor (ER) negative (defined as less than 1% ER by immunohistochemistry [IHC]) and progesterone receptor (PR) negative breast cancer (defined as less than 1% PR staining by IHC)
  • 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
  • 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 three months following completion of study therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • All patients must provide archival tissue block or paraffin sample from archival tissue block (approximately 10 sections) for use in pharmacodynamic correlative studies (NOT required for patients enrolled on the dose escalation for intermittent ABT-888 portion of the study)

Exclusion Criteria:

  • 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 active seizure or a history of seizure
  • 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
    • Cardiac arrhythmia or
    • Psychiatric illness or social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ABT-888
  • Patients who are unable to reliably tolerate and/or receive oral medications
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00576654

Locations
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Patricia M. LoRusso    203-785-5944    patricia.lorusso@yale.edu   
Principal Investigator: Patricia M. LoRusso         
United States, Maryland
University of Maryland/Greenebaum Cancer Center Withdrawn
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Sara M. Tolaney    617-632-2335    stolaney@partners.org   
Principal Investigator: Sara M. Tolaney         
United States, Michigan
Wayne State University/Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Amy M. Weise    313-576-8599    weisea@karmanos.org   
Principal Investigator: Amy M. Weise         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Patricia LoRusso Yale University
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00576654     History of Changes
Other Study ID Numbers: NCI-2009-01057
NCI-2009-01057 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HIC 1410014852
2007-014
HIC1410014852
CDR0000579642
7977 ( Other Identifier: Yale University )
7977 ( Other Identifier: CTEP )
P30CA016359 ( US NIH Grant/Contract Award Number )
R21CA135572 ( US NIH Grant/Contract Award Number )
U01CA062487 ( US NIH Grant/Contract Award Number )
U01CA062490 ( US NIH Grant/Contract Award Number )
UM1CA186689 ( US NIH Grant/Contract Award Number )
UM1CA186709 ( US NIH Grant/Contract Award Number )
Study First Received: December 18, 2007
Last Updated: June 23, 2017

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lung Neoplasms
Lymphoma
Breast Neoplasms
Carcinoma
Neoplasms
Pancreatic Neoplasms
Ovarian Neoplasms
Hodgkin Disease
Colonic Neoplasms
Neoplasms, Second Primary
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Ovarian Diseases

ClinicalTrials.gov processed this record on June 26, 2017