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Talotrexin in Treating Patients With Advanced or Recurrent Solid Tumors

Sponsor
Dana-Farber Cancer Institute (Other)
Overall Status
Completed
CT.gov ID
NCT00098514
Collaborator
National Cancer Institute (NCI) (NIH)
53
Enrollment
1
Location
7
Arms
89
Actual Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as talotrexin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying side effects, best way to give, and best dose of talotrexin in treating patients with advanced or recurrent solid tumors.

Condition or Disease Intervention/Treatment Phase
  • Drug: talotrexin ammonium
 Phase 1

Detailed Description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of talotrexin in patients in patients with advanced or recurrent solid tumors.

  • Determine the safety of this drug in these patients.

  • Determine the dose-limiting toxic effects of this drug in these patients.

Secondary

  • Determine the pharmacokinetics of this drug in these patients.

  • Correlate pharmacokinetic parameters of this drug or patient characteristics with drug-related toxicity in these patients.

  • Determine, preliminarily, the antitumor efficacy of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive talotrexin IV over 5 minutes on day 1 OR days 1 and 8 OR days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of talotrexin 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. An additional 6-10 patients are treated at the MTD.

Patients are followed at 1 month.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 9-12 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
53 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
There were 7 potential PT523 single agent dose levels to be evaluated in this phase I studyThere were 7 potential PT523 single agent dose levels to be evaluated in this phase I study
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study Of PT523 In Patients With Solid Tumors
Actual Study Start Date :
Dec 1, 2003
Actual Primary Completion Date :
Mar 1, 2007
Actual Study Completion Date :
May 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Level 1a

10 mg/m2 dose of PT523 administered day 1 of a 28-day cycle as a 5 minute IV infusion (IV bolus)

Drug: talotrexin ammonium
Experimental: Dose Level 1b

5 mg/m2 dose of PT523 administered days 1 and 8 of a 28-day cycle as a 5 minute IV infusion

Drug: talotrexin ammonium
Experimental: Dose Level 1c

3.33 mg/m2 dose of PT523 administered days 1, 8 and 15 of a 28-day cycle as a 5 minute IV infusion

Drug: talotrexin ammonium
Experimental: Dose Level 2

5 mg/m2 dose of PT523 administered days 1, 8 and 15 of a 28-day cycle as a 5 minute IV infusion

Drug: talotrexin ammonium
Experimental: Dose Level 3

7.5 mg/m2 dose (or 6.7 mg/m2 depending on observed toxicity) of PT523 administered days 1, 8 and 15 of a 28-day cycle as a 5 minute IV infusion

Drug: talotrexin ammonium
Experimental: Dose Level 4

11.25 mg/m2 dose (or 9 mg/m2 depending on observed toxicity) of PT523 administered days 1, 8 and 15 of a 28-day cycle as a 5 minute IV infusion

Drug: talotrexin ammonium
Experimental: Dose Level 5

17 mg/m2 dose (or 12 mg/m2 depending on observed toxicity) of PT523 administered days 1, 8 and 15 of a 28-day cycle as a 5 minute IV infusion

Drug: talotrexin ammonium

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 120 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    DISEASE CHARACTERISTICS:

    • Diagnosis of malignant solid tumor

    • Metastatic or inoperable disease

    • No known curative or survival-prolonging palliative therapy exists OR failed these prior therapies

    • No leukemia

    • No primary CNS tumor

    • No third-space fluid collection (i.e., pleural effusion, ascites)

    • Clinically insignificant small pleural or peritoneal effusions identified by CT scan, MRI, or other diagnostic test allowed

    • No active* brain metastases, including the following:

    • Evidence of cerebral edema by CT scan or MRI

    • Progression since prior imaging study

    • Requirement for steroids

    • Clinical symptoms of/from brain metastases NOTE: *Treated and/or stable brain metastasis allowed provided patient is asymptomatic

    PATIENT CHARACTERISTICS:

    Age

    • 18 and over

    Performance status

    • ECOG 0-2

    Life expectancy

    • At least 2 months

    Hematopoietic

    • Absolute neutrophil count ≥ 1,500/mm^3

    • Platelet count ≥ 100,000/mm^3

    • RBC folate ≥ lower limit of normal

    Hepatic

    • Bilirubin normal

    • SGOT and SGPT ≤ 2.5 times upper limit of normal

    Renal

    • Creatinine clearance ≥ 50 mL/min

    Other

    • Not pregnant or nursing

    • Negative pregnancy test

    • Fertile patients must use effective contraception

    • No other uncontrolled serious medical or psychiatric illness

    PRIOR CONCURRENT THERAPY:

    Biologic therapy

    • No prior bone marrow transplantation

    Chemotherapy

    • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

    Endocrine therapy

    • See Disease Characteristics

    Radiotherapy

    • More than 3 weeks since prior radiotherapy

    • No concurrent radiotherapy

    Surgery

    • At least 3 weeks since prior surgery

    Other

    • Recovered from prior therapy

    • More than 3 weeks since prior antifolate therapy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston Massachusetts United States 02115

    Sponsors and Collaborators

    • Dana-Farber Cancer Institute
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Joseph Paul Eder, MD,

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Geoffrey Shapiro, MD, PhD, Director, Early Drug Development Center, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT00098514
    Other Study ID Numbers:
    • 03-183
    • P30CA006516
    • CDR0000400150
    • NCI-6400
    • DFCI-IRB-03183
    • HANABIO-DFCI-02000
    First Posted:
    Dec 8, 2004
    Last Update Posted:
    Dec 18, 2017
    Last Verified:
    Dec 1, 2017
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Geoffrey Shapiro, MD, PhD, Director, Early Drug Development Center, Dana-Farber Cancer Institute
    unspecified adult solid tumor, protocol specific
    Additional relevant MeSH terms:
    Neoplasms

    Study Results

    No Results Posted as of Dec 18, 2017