Completed

3-AP and Doxorubicin In Treating Patients With Metastatic or Refractory Solid Tumors

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What is being tested

triapine

+ doxorubicin hydrochloride
+ laboratory biomarker analysis
Drug
Other
Who is being recruted

Unspecified Adult Solid Tumor, Protocol Specific

Over 18 Years
+26 Eligibility Criteria

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 1
Interventional
Study Start: January 2004

See protocol details

Summary

Principal SponsorNational Cancer Institute (NCI)
Last updated: May 16, 2013
Sourced from a government-validated database.Claim as a partner
Study start date: January 1, 2004Actual date on which the first participant was enrolled.

This phase I trial is studying the side effects and best dose of 3-AP and doxorubicin in treating patients with metastatic or refractory solid tumors. Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. 3-AP may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth and may help doxorubicin kill more cancer cells by making them more sensitive to the drug. PRIMARY OBJECTIVES: I. To find the maximal tolerated dose for the combination of doxorubicin and Triapine® in patients with refractory solid tumors. SECONDARY OBJECTIVES: I. To find the severity and frequency of toxicity associated with this combination and to observe for and record any antitumor activity. TERTIARY OBJECTIVES: I. To evaluate the effect of Triapine®/doxorubicin on the ribonucleotide reductase tyrosyl radical in vivo by EPR spectroscopy in buccal mucosal cells, peripheral blood lymphocytes and in tumor biopsies. Formation of low molecular weight iron-Triapine® chelates will also be assessed by EPR. II. To evaluate the effect of Triapine®/doxorubicin on cell cycle in vivo by measuring S-phase arrest in buccal mucosal cells. III. To evaluate the effect of Triapine®/doxorubicin on MDR gene expression and polymorphisms in blood. IV. To evaluate the effect of Triapine®/doxorubicin on ribonucleotide reductase R2 mRNA and immunohistochemistry. V. To evaluate the pharmacokinetic profile of the combination. VI. To measure the formulation of circulating isoprostanes as an indicator of oxidative stress with this combination. OUTLINE: This is a dose-escalation study of 3-AP (Triapine\^®). Patients receive doxorubicin IV over 15 minutes on day 1 and 3-AP (Triapine®) IV over 2 hours on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. 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. Once the MTD is determined, an additional 6 patients are treated at that dose level. Patients are followed until disease progression.

Official TitleA Phase I Study of Triapine® in Combination With Doxorubicin in Refractory Tumors 
Principal SponsorNational Cancer Institute (NCI)
Last updated: May 16, 2013
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
36 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment: Participants are split into separate groups, each receiving a different treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Unspecified Adult Solid Tumor, Protocol Specific
Criteria
16 inclusion criteria required to participate
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative chemotherapy measures do not exist or are no longer effective
Patients must not have previously received anthracyclines
Patients must not have received radiation to > 25% of bone marrow
ECOG performance status =< 2

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10 exclusion criteria prevent from participating
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients with grade =< 1 adverse events from prior therapies are eligible at the investigator's discretion
Patients may not be receiving any other investigational agents
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

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Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
One single intervention group 

is designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Patients receive doxorubicin IV over 15 minutes on day 1 and 3-AP (Triapine®) IV over 2 hours on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine®) until the 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. Once the MTD is determined, an additional 6 patients are treated at that dose level.
Study Objectives
Primary Objectives

Hematologic toxicity measures of thrombocytopenia, neutropenia and leukopenia will be assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values). Nonhematologic toxicities such as diarrhea and stomatitis will be evaluated via the ordinal CTC standard toxicity grading only. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
Secondary Objectives

Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 1 location
Suspended
University of Wisconsin Hospital and ClinicsMadison, United StatesSee the location
CompletedOne Study Center