Irinotecan and ABT-888 in Treating Patients With Metastatic or Unresectable Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00576654
First received: December 18, 2007
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

This phase I trial is studying the side effects and best dose of irinotecan given together with ABT-888 in treating patients with metastatic or unresectable cancer. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. ABT-888 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving irinotecan together with ABT-888 may kill more cancer cells.


Condition Intervention Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult Non-Hodgkin Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Splenic Marginal Zone Lymphoma
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Adult Non-Hodgkin Lymphoma
Stage III Adult T-cell Leukemia/Lymphoma
Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Mycosis Fungoides/Sezary Syndrome
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Adult Non-Hodgkin Lymphoma
Stage IV Adult T-cell Leukemia/Lymphoma
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Mycosis Fungoides/Sezary Syndrome
Stage IV Small Lymphocytic Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Waldenström Macroglobulinemia
Drug: irinotecan hydrochloride
Drug: veliparib
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
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:
  • Optimal biological dose of study drugs, defined as the maximal decrease in PAR [ Time Frame: Up to day 9 of course 1 ] [ Designated as safety issue: Yes ]
  • Maximum administered dose of study drugs, defined as the dose level at which at least 2 of 6 patients develop DLT [ Time Frame: Up to 21 days ] [ Designated as safety issue: Yes ]
  • Maximum tolerated dose of study drugs, defined as the dose at which no more than 1 patient of 6 develops DLT [ Time Frame: Up to 21 days ] [ Designated as safety issue: Yes ]
  • Recommend phase II dose 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 [ Time Frame: Up to 21 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: December 2007
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (irinotecan hydrochloride and ABT-888)
Patients receive irinotecan hydrochloride IV over 90 minutes on days 1 and 8 and ABT-888 PO BID on days 0-14 (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
  • CPT-11
  • irinotecan
  • U-101440E
Drug: veliparib
Given PO
Other Name: ABT-888
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Bilirubin =< 1.5 times upper limit of normal (ULN)
  • Patients must have tumors determined to be easily accessible for biopsy (e.g. pleural-based lesions, peripheral lymph nodes, soft tissue metastases, or large liver metastases)
  • Archival tissue block or paraffin sample from archival tissue block (approximately 10 sections) for use in pharmacodynamic correlative studies must be available
  • No known active brain metastases

    • Patients with previously treated brain metastases are eligible, provided they are not accompanied by seizures and a baseline brain magnetic resonance imaging (MRI) scan demonstrates no current evidence of brain metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 12 weeks
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times ULN (=< 5 times ULN if liver metastases are present)
  • Alkaline phosphatase =< 2.0 times ULN (=< 5 times ULN if bone or liver metastases are present)
  • Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min
  • Ability to understand and the willingness to sign a written informed consent document
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for 3 months after completion of study treatment
  • Must be able to reliably tolerate and/or receive oral medications
  • No history of allergic reactions attributed to the following:

    • Camptothecin derivatives (e.g., topotecan hydrochloride, irinotecan hydrochloride, or exatecan mesylate)
    • Any ingredients contained within the liquid irinotecan hydrochloride solution (e.g., sorbitol)
    • Any antiemetics or antidiarrheals appropriate for administration with study therapy (e.g., loperamide or dexamethasone)
  • No prior history of seizures
  • No uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situations that would limit compliance with study requirements
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • More than 3 weeks since prior minimal radiotherapy (i.e., =< 5% of total marrow volume)
  • More than 4 weeks since prior radiotherapy (i.e., > 5% of total marrow volume)
  • No prior radiotherapy to >= 50% of total marrow volume
  • Histologically or cytologically confirmed metastatic or unresectable malignancy meeting 1 of the following criteria:

    • Standard curative or palliative measures do not exist or are no longer effective
    • Irinotecan hydrochloride is considered to be a viable therapy regimen
  • 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 with solid hematologic malignancies (Hodgkin or non-Hodgkin lymphoma) are eligible provided a bone marrow has been performed within 6 weeks of treatment
  • Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) guidelines
  • Patients must be negative for carrying the UGT1A1*28 allele (also called (TA)7)
  • More than 4 weeks since prior experimental (i.e., non-Food and Drug Administration [FDA] approved) therapy or immunotherapy and recovered
  • Males receiving treatment for prostate cancer must be maintained at castrate levels of testosterone by continuation of luteinizing-releasing hormone agonists
  • No cytochrome P450 CYP3A4 isoform-inducing drugs (e.g. phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, ketoconazole, St. John's Wort)
  • No other investigational agents within 4 weeks of study entry
  • No chronic growth factor support (e.g., filgrastim [G-CSF], pegfilgrastim) for maintenance of white blood cell counts or granulocyte counts
  • No other concurrent anticancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except medications for supportive care that may potentially have an anticancer effect (i.e., megestrol acetate, bisphosphonates) started 1 month prior to study
  • Patients with active seizure or a history of seizure are excluded
  • 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 MRI scan prior to study entry demonstrates no current evidence of brain metastases; all patients with CNS metastases must be stable for > 3 months after treatment and off steroid treatment prior to study enrollment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00576654

Locations
United States, Arizona
Translational Genomics Research Institute
Phoenix, Arizona, United States, 85004
United States, Maryland
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201-1595
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0944
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Investigators
Principal Investigator: Patricia LoRusso Barbara Ann Karmanos Cancer Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00576654     History of Changes
Other Study ID Numbers: NCI-2009-01057, NCI-2009-01057, CDR0000579642, 2007-014, 7977, U01CA062490, U01CA062487, P30CA022453
Study First Received: December 18, 2007
Last Updated: February 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Mantle-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on April 17, 2014