Brief Title
3-AP and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma
Official Title
A Phase I Study of a Prolonged Infusion of Triapine in Combination With a Fixed Dose Rate of Gemcitabine in Patients With Advanced Solid Tumors and Lymphomas
Brief Summary
This phase I trial is studying the best dose of 3-AP and the side effects of giving 3-AP
together with gemcitabine in treating patients with advanced solid tumors or lymphoma. Drugs
used in chemotherapy, such as 3-AP and gemcitabine (GEM), work in different ways to stop the
growth of cancer cells, either by killing the cells or by stopping them from dividing. 3-AP
may help gemcitabine kill more cancer cells by making the cells more sensitive to the drug.
3-AP may also stop the growth of tumor cells by blocking some of the enzymes needed for cell
growth.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximal tolerable dose (MTD) of 3-AP administered as a 24 hour infusion
in combination with and fixed-dose gemcitabine hydrochloride (GEM) in patients with advanced
solid tumors or lymphomas.
SECONDARY OBJECTIVES:
I. To define the qualitative and quantitative toxicities of the 3-AP/GEM combination in
regard to organ specificity, time course, predictability, and reversibility.
II. To document the therapeutic response of this combination in those patients when possible.
III. To measure deoxycytidine triphosphate (dCTP) levels in peripheral blood mononuclear
cells (PBMCs) before and after treatment at specified times and try to correlate findings to
activity and toxicity of 3-AP.
IV. To perform limited pharmacokinetic analysis.
OUTLINE: This is a dose-escalation study of 3-AP (Triapine®).Patients receive 3-AP
(Triapine®) IV over 24 hours followed by gemcitabine hydrochloride IV over 100-125 minutes on
days 1 and 8. Treatment repeats every 3 weeks for 12 courses in the absence of disease
progression or unacceptable toxicity.
Patients achieving complete response (CR) receive 1 additional course of therapy beyond
documented CR.Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine®) until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.After completion of study
treatment, patients are followed periodically for 2 years.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
MTD as assessed by the number of patients with dose-limiting toxicity (DLT)
Secondary Outcome
Toxicity as assessed using the NCI Common Toxicity Criteria, Version 3.0
Condition
Anaplastic Large Cell Lymphoma
Intervention
gemcitabine hydrochloride
Study Arms / Comparison Groups
Treatment (gemcitabine hydrochloride, triapine)
Description: Patients receive 3-AP (Triapineî) IV over 24 hours followed by gemcitabine hydrochloride IV over 100-125 minutes on days 1 and 8. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
30
Start Date
June 2006
Primary Completion Date
October 2012
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed advanced solid tumors or lymphoma
- Disease considered incurable using standard treatment
- ECOG performance status ≤ 2
- Life expectancy > 12 weeks
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Total bilirubin normal
- AST/ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception prior to and during study treatment
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to 3-AP (Triapine®) and/or gemcitabine hydrochloride
- No known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- No 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 situation that would limit compliance with
study requirements
- No pulmonary disease (e.g., dyspnea at rest, supplemental oxygen requirement, or
baseline oxygen saturation < 92%)
- Prior gemcitabine hydrochloride allowed if given as a standard 30-minute infusion
- At least 4 weeks since prior gemcitabine hydrochloride
- Patient may have received < 2 lines of chemotherapy in the metastatic setting
- No prior 3-AP (Triapine®) or fixed-dose gemcitabine hydrochloride
- At least 6 weeks since prior nitrosoureas or mitomycin C
- More than 3 weeks since prior radiotherapy
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy in HIV-positive patients
- No other concurrent anticancer agents or therapies
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Tanios Bekaii-Saab, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00293345
Organization ID
NCI-2009-00119
Secondary IDs
NCI-2009-00119
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Tanios Bekaii-Saab, Principal Investigator, Ohio State University
Verification Date
September 2013