Know Cancer

or
forgot password

An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Extensive Stage Small Cell Lung Cancer, Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor, Recurrent Breast Cancer, Recurrent Melanoma, Recurrent Non-small Cell Lung Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Ovarian Germ Cell Tumor, Recurrent Small Cell Lung Cancer, Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor, Stage IV Breast Cancer, Stage IV Melanoma, Stage IV Non-small Cell Lung Cancer, Stage IV Ovarian Epithelial Cancer, Stage IV Ovarian Germ Cell Tumor, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors


PRIMARY OBJECTIVES:

I. To determine the pharmacokinetics and pharmacodynamics of ABT-888 (veliparib) in patients
with varying degrees of renal or hepatic dysfunction.

II. To determine the maximum-tolerated dose (MTD) of ABT-888 in combination with carboplatin
and paclitaxel for patients with varying degrees of liver or kidney dysfunction.

III. To provide dosing recommendations for ABT-888 in combination with carboplatin and
paclitaxel based on degree of hepatic and renal impairment.

SECONDARY OBJECTIVES:

I. To define the dose-limiting toxicity (DLT) and other toxicities associated with the use
of this combination in patients with varying degrees of renal or hepatic dysfunction.

II. To evaluate the pharmacokinetic parameters of ABT-888, carboplatin, and paclitaxel when
administered as a combination in patients with varying degrees of renal of hepatic
dysfunction.

III. To evaluate the pharmacodynamic measurement of poly-ADP-ribosylated (PAR) and platinum
adducts in tumor cells associated with the use of this combination in patients with varying
degrees of renal or hepatic dysfunction.

OUTLINE: This is a multicenter, dose-escalation study of veliparib. Patients are stratified
according to degree of renal dysfunction (normal vs moderate vs severe vs very severe) or
hepatic dysfunction (mild vs mild with transaminase elevation vs moderately severe vs
severe).

Patients receive veliparib* orally (PO) twice daily (BID) on days 1-7 and paclitaxel
intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 3. Courses repeat
every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Blood and hair follicle samples are collected at baseline, on days -5 or -6, and on day 3 of
course 1 for pharmacokinetic and pharmacodynamic studies. Tumor tissue biopsies may also be
collected at baseline and on day 3.

After completion of study therapy, patients are followed up for 4 weeks.

NOTE: * All patients receive a single dose of veliparib PO on day -6 before course 1 (except
patients with very severe renal dysfunction who receive veliparib on day -5 or -6 to
coincide with a dialysis day).


Inclusion Criteria:



- Patients must have histologically confirmed malignancy that is radiologically
evaluable and metastatic or unresectable, for which standard curative or palliative
measures do not exist or are no longer effective, and for which there is expectation
of response to the combination of carboplatin/paclitaxel (i.e., lung, ovarian,
breast, melanoma, head and neck, endometrial, urothelial, testicular, esophageal,
carcinoma of unknown primary); or indications not listed, eligibility based on
disease must be verified by the principal Investigator before they are considered

- 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 >= 100,000/mcL

- Hemoglobin >= 8.0 g/dL

- Patients with all degrees of renal dysfunction are allowed, including patients on
hemodialysis; patients with mild to severe hepatic dysfunction are allowed as defined
below:

- Total bilirubin =< 5 x upper limit of normal (ULN) AND aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) =< 10 x ULN For
patients with a recently placed biliary stent, patients should have consistent
results within a hepatic group from two laboratory readings within 3 days apart,
taken at least 10 days following biliary stent placement; for patients with a
biliary stent placed over 2 months ago, no obstruction or blockage can have
occurred within the last 2 months

- 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 and
for the duration of study participation; 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

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 whose adverse event
due to agents administered more than 4 weeks earlier have not resolved or stabilized;
patients who have been administered ABT-888 as part of a single or combination, Phase
0 or I study, should not necessarily be excluded from participating in this study
solely because of receiving prior ABT-888

- Patients may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ABT-888 or other agents used in study

- Peripheral neuropathy of severity greater than grade 1

- Inability to take oral medications on a continuous basis

- Evidence of bleeding diathesis

- Patients with central nervous system (CNS) metastases must be stable after therapy
for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for
at least 3 months and must be off steroid treatment prior to study enrollment

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/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; these potential risks may also apply to other
agents used in this study

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible; however, HIV-positive patients without an acquired immune
deficiency syndrome (AIDS)-defining diagnosis who are not receiving agents with the
potential for pharmacokinetic (PK) interactions with ABT-888 may be eligible

- Patients with both hepatic and renal dysfunction will also be excluded

- Patients who received and progressed on the combination of carboplatin/paclitaxel
will not be eligible

- Active seizure or history of seizure disorder

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD of veliparib in combination with carboplatin and paclitaxel using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

Outcome Time Frame:

Up to day 21

Safety Issue:

Yes

Principal Investigator

Hussein Tawbi

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02500

NCT ID:

NCT01366144

Start Date:

June 2011

Completion Date:

Related Keywords:

  • Extensive Stage Small Cell Lung Cancer
  • Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor
  • Recurrent Breast Cancer
  • Recurrent Melanoma
  • Recurrent Non-Small Cell Lung Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Ovarian Germ Cell Tumor
  • Recurrent Small Cell Lung Cancer
  • Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor
  • Stage IV Breast Cancer
  • Stage IV Melanoma
  • Stage IV Non-Small Cell Lung Cancer
  • Stage IV Ovarian Epithelial Cancer
  • Stage IV Ovarian Germ Cell Tumor
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Breast Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Melanoma
  • Small Cell Lung Carcinoma
  • Neoplasms, Germ Cell and Embryonal
  • Germinoma
  • Ovarian Neoplasms
  • Neoplasms
  • Neoplasms, Glandular and Epithelial

Name

Location

Albert Einstein College of MedicineBronx, New York  10461
Johns Hopkins UniversityBaltimore, Maryland  21205
Memorial Sloan Kettering Cancer CenterNew York, New York  10021
University of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania  15213
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Montefiore Medical CenterBronx, New York  10467-2490
City of HopeDuarte, California  91010
Case Western Reserve UniversityCleveland, Ohio  44106
Emory UniversityAtlanta, Georgia  30322
Wayne State UniversityDetroit, Michigan  48202
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Penn State Milton S Hershey Medical CenterHershey, Pennsylvania  17033
City of Hope- South Pasadena Cancer CenterSouth Pasadena, California  91030
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer CenterCleveland, Ohio  44106