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Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00084877

Irinotecan and 3-AP in Treating Patients With Metastatic or Unresectable Solid Tumors

A Phase 1 study testing triapine, irinotecan hydrochloride and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial is studying the side effects and best dose of irinotecan and 3-AP in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy such as irinotecan work in different ways to stop tumor cells from dividing so they stop growing or die. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
triapine, irinotecan hydrochloride and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
Mar 2004to Jul 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 irinotecan
  • Patients must not have received radiation to > 25% of bone marrow
  • ECOG performance status =< 2
  • Life expectancy of greater than 12 weeks
  • Leukocytes >= 3,000/μl
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  • Absolute neutrophil count >= 1,500/μl
  • Platelets >= 100,000/μl
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
  • Creatinine =< 1.5 mg/dl OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Patients must have measurable or evaluable disease
  • Patients must have baseline screening for G6PD (glucose-6-phosphate dehydrogenase) deficiency; G6PD must be no lower than the lower limit of normal prior to starting study treatment; patients who are above the upper limit of normal may enroll in the trial
  • The effects of Triapine® on the developing human fetus are unknown; for this reason and because heterocyclic carboxaldehyde thiosemicarbazones as well as other therapeutic agents used in this trial are known to be teratogenic, 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
  • Patients must have a baseline screening test for UGT1A1; the UGT1A1 cannot be the 7/7 genotype; patients who have any other combinations (6/6, 6/7, 5/7, etc.) may enroll in the trial

Who cannot join

  • 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
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Triapine® or other agents used in study
  • 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 because Triapine® is a heterocyclic carboxaldehyde thiosemicarbazone with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Triapine®, breastfeeding should be discontinued if the mother is treated with Triapine®; these potential risks may also apply to other agents used in this study
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  • Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with Triapine® or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
  • Patients with known G6PD deficiency are excluded
  • Patients with a history of myocardial infarction or severe pulmonary disease requiring oxygen are excluded
  • Because of the potential for enzyme-inducing anticonvulsant agents (EIACAs) to alter the metabolism and pharmacokinetics of irinotecan, patients who are taking EIACAs are excluded
  • Metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, had a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry; also the patient must not be undergoing acute steroid therapy or taper
  • Patients with UGT1A1 7/7 genotype are excluded

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

Other trials in United States

About this study

Official title: A Phase I Study of Triapine® in Combination With Irinotecan in Refractory Tumors

This phase I trial is studying the side effects and best dose of irinotecan and 3-AP in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy such as irinotecan 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 their growth and may help irinotecan kill more tumor cells by making them more sensitive to the drug.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To find the maximal tolerated dose for the combination of irinotecan and Triapine® in patients with refractory solid tumors.

SECONDARY OBJECTIVES:

  1. To find the severity and frequency of toxicity associated with this combination and to observe for and record any antitumor activity.

TERTIARY OBJECTIVES:

  1. To evaluate the effect of Triapine®/irinotecan on the ribonucleotide reductase tyrosyl radical in vivo by Electron Paramagnetic Spectroscopy (EPR) 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® /irinotecan on cell cycle in vivo by measuring S-phase arrest in buccal mucosal cells.

III. To evaluate the effect of Triapine® /irinotecan on MDR gene expression and polymorphisms in blood.

IV. To evaluate the effect of Triapine® /irinotecan on ribonucleotide reductase R2 mRNA and Immunohistochemistry.

  1. To evaluate the pharmacokinetic profile of the combination.

OUTLINE: This is a dose-escalation study.

Patients receive irinotecan IV over 1 hour on day 1 and 3-AP (Triapine®) IV over 2 hours on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan and 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, 6 additional patients are treated at that dose.

Patients are followed until disease progression.

Being tested
triapine, irinotecan hydrochloride, laboratory biomarker analysis, pharmacological study

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • triapineDrug

    Also called 3-AP, OCX-191

    Given IV

  • irinotecan hydrochlorideDrug

    Also called Campto, Camptosar, CPT-11, irinotecan

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00084877
Study groupRoleWhat they receive
Treatment (triapine, irinotecan hydrochloride)ExperimentalPatients receive irinotecan IV over 1 hour on day 1 and 3-AP (Triapine®) IV over 2 hours on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan and 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, 6 additional patients are treated at that dose.
Receives: Drug: triapine; Drug: irinotecan hydrochloride; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number and severity of toxicity incidents categorized via CTC standard toxicity grading

    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.

    Measured: Up to 4 years

Secondary outcomes (1)

  1. Number of responses

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

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jun 2004 (estimated)
  2. Study startMar 2004
  3. Primary completionJul 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00084877
Sponsor's protocol ID
NCI-2013-00013
Other IDs
CO 03903, NCI-6264, WCCC-CO-03903, U01CA062491
Status last verified
May 2013
First submitted
10 Jun 2004
Last updated
16 May 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing triapine, irinotecan hydrochloride and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 May 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number and severity of toxicity incidents categorized via CTC standard toxicity grading (time frame: Up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00084877.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2013.

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