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Talotrexin in Treating Patients With Advanced or Recurrent Solid Tumors

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ClinicalTrials.gov Identifier: NCT00098514
Recruitment Status : Completed
First Posted : December 8, 2004
Last Update Posted : December 18, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute

December 7, 2004
December 8, 2004
December 18, 2017
December 2003
March 2007   (Final data collection date for primary outcome measure)
Not Provided
Not Provided
Complete list of historical versions of study NCT00098514 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Talotrexin in Treating Patients With Advanced or Recurrent Solid Tumors
A Phase I Study Of PT523 In Patients With Solid Tumors

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.

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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Intervention Model Description:
There were 7 potential PT523 single agent dose levels to be evaluated in this phase I study
Masking: None (Open Label)
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
Drug: talotrexin ammonium
  • 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)
    Intervention: 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
    Intervention: 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
    Intervention: 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
    Intervention: 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
    Intervention: 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
    Intervention: 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
    Intervention: Drug: talotrexin ammonium
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
53
Not Provided
May 2011
March 2007   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 120 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00098514
03-183
P30CA006516 ( U.S. NIH Grant/Contract )
CDR0000400150
NCI-6400
DFCI-IRB-03183
HANABIO-DFCI-02000
Yes
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
Not Provided
Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Joseph Paul Eder, MD
Dana-Farber Cancer Institute
December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP