Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial
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
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.
| Status | Completed |
| Enrollment | 30 |
| Est. completion date | |
| Est. primary completion date | October 2012 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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 |
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Ohio State University Medical Center | Columbus | Ohio |
| Lead Sponsor | Collaborator |
|---|---|
| National Cancer Institute (NCI) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | MTD as assessed by the number of patients with dose-limiting toxicity (DLT) | MTD is the maximum dose level with fewer than 2 of 3/6 patients experiencing DLT. The study uses standard method phase I design of dose escalation. DLT will be defined as greater or equal to Grade 3 non-hematologic or greater or equal to Grade 4 hematologic adverse event EXCEPT: greater or equal to Grade 3 nausea and greater or equal to Grade 3 vomiting that improves with antiemetic therapy; greater or equal to Grade 3 diarrhea that improves with Lomotil; and greater or equal to Grade 4 Neutropenia that recovers to less or equal to Grade 3 within 7 days of first identification. | Observed clinically for 4 hours after each 3-AP infusion during the first cycle of treatment | Yes |
| Secondary | Toxicity as assessed using the NCI Common Toxicity Criteria, Version 3.0 | Toxicities include neutropenia grade 4 (<500/mm3), neutropenic fever (grade 4 neutropenia and greater than or equal to grade 2 fever), thrombocytopenia Grade 3-4 (<50000/mm3), and non-hematologic toxicities grades 3-4. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for adverse event reporting. | Observed clinically for 4 hours after each 3-AP infusion during the first cycle of treatment and monitored until disease progression or for a maximum of 24 months following termination of treatment | Yes |
| Secondary | Therapeutic response | Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Complete Response (CR) is the disappearance of all target lesions. Partial Response (PR) requires at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. The results will be purely descriptive. | Tumor and radiologic measurements every 8 weeks from start of treatment. In addition to a baseline scan, confirmatory scans will also be obtained 8 weeks following initial documentation of an objective response. | No |
| Secondary | Duration of overall response | The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). | Baseline until disease progression or for a maximum of 24 months following termination of treatment. | No |
| Secondary | Duration of stable disease | Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started. | Baseline until disease progression or for a maximum of 24 months following termination of treatment. | No |
| Secondary | Levels of dCTP in PBMCs correlated to activity and toxicity of 3-AP | If dCTP levels are diminished by 3-AP, there is a real possibility of ribonucleotide reductase (RR) inhibition in tumor cells with a higher growth fraction (known to have elevated RR levels). It will also be possible to correlate the steady state levels of 3-AP with the concentration of dCTP in circulating cells. The RT-PCR of PBMCs before and after infusion would be helpful to reassure that the change of dCTP pool is correlated with 3-AP inhibiting RR. | PMBCs isolated immediately before and after 3-AP infusion (day 1), but before GEM is started on (day 2) on both course 1 and course 2 of treatment | No |
| Secondary | Pharmacokinetics as assessed by steady state concentration (Css) of 3-AP in serum | On the first day of infusion (course 1 only) during the last 4 hours of 3-AP infusion | No |
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