Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

ABT-888 and Topotecan in Treating Patients With Advanced or Refractory Solid Tumors, Lymphoma, or Chronic Lymphocytic Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Biomarker/Laboratory analysis, Treatment Active 18 and over NCI NCI-07-C-0203 P7241, 7981, NCT00553189

Special Category: NIH Clinical Center trial

Objectives

Primary

1. Establish the safety and tolerability of the combination of ABT-888 with topotecan hydrochloride in patients with refractory solid tumors, lymphoma, or chronic lymphocytic leukemia.
2. Establish the maximum tolerated dose of the combination of ABT-888 with topotecan hydrochloride.

Secondary

1. Evaluate the pharmacokinetics of each agent in combination.
2. Determine the effects of the study treatment on the level of PARP inhibition and DNA damage in peripheral blood mononuclear cells and tumor samples.

Entry Criteria

Disease Characteristics:

• Histologically confirmed solid tumors and lymphoid malignancies (i.e., lymphoma or chronic lymphocytic leukemia) refractory to standard therapy OR with no acceptable standard treatment options
  • Lymphoid malignancies allowed if disease has progressed following standard therapy and if stem cell transplantation is not indicated or has been refused
  .
• No known brain metastases

Prior/Concurrent Therapy:

• Prior therapy must have been completed ≥ 4 weeks prior to enrollment on protocol and the participant must have recovered to eligibility levels (CTCAE grade ≤ 1) from prior toxicity
• Prior radiation or surgery should have been completed ≥ 4 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels
• Patients must be ≥ 2 weeks since any investigational agent administered as part of a Phase 0 study and should have recovered to eligibility levels from any toxicities
• No prior chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C) and recovered from adverse events
  • Patients who have received prior ABT-888 as part of a single- or limited-dosing study (e.g., Phase 0 study) should not be excluded solely because of receiving prior ABT-888
  • Patients who have received prior topotecan hydrochloride (TPT) should not be excluded solely because of receiving prior TPT
• No other concurrent chemotherapy

Patient Characteristics:

• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Life expectancy > 3 months
• ANC ≥ 1,500/µL
• Platelet count ≥ 100,000/µL
• Total bilirubin < 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine < 1.5 times ULN or creatinine clearance ≥ 60 mL/min
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry, for the duration of study participation, and for 3 months after completion of study
• Not pregnant
• Negative pregnancy test
• Patients must discontinue breast feeding during and for 30 days after completion of study treatment
• No uncontrolled intercurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Prolonged QTc interval (> 500 msec)
  • Psychiatric illness/social situations that would limit compliance with study requirements
• No history of seizures

Expected Enrollment

Outcomes

Maximum tolerated dose

Evaluation of the pharmacokinetics of each agent
Level of PARP inhibition

Outline

• Course 1: Patients receive topotecan hydrochloride (TPT) IV over 30 minutes on days 1-5. Patients then receive oral ABT-888 twice daily on days 2-5. Two weeks later, patients proceed to course 2.



• Course 2 and beyond: Patients receive oral ABT-888 twice daily and TPT IV on days 1-5. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression.

Peripheral blood monocyte samples for pharmacodynamic analysis are obtained on days -8, 1, and 2 of course 1 over a period of 24 hours each. Blood sampling for pharmacokinetic analysis is performed at multiple time points over a 24-hour period on days -8, 1, and 2 during course 1. Tumor biopsies are obtained during course 1 on days -8 and 2 for pharmacodynamic studies.

After completion of study therapy, patients are followed for 30 days.

Trial Contact Information

Trial Lead Organizations

National Cancer Institute

Shivaani Kummar, MD, Protocol chair		Ph: 301-435-5402 Email: kummars@exchange.nih.gov

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Registry Information
Official Title		A Phase I Study of ABT-888 in Combination With Topotecan Hydrochloride in Adults With Refractory Solid Tumors and Lymphomas
Trial Start Date		2007-08-28
Trial Completion Date		2009-02-18 (estimated)
Registered in ClinicalTrials.gov		NCT00553189
Date Submitted to PDQ		2007-08-20
Information Last Verified		2008-04-06