Clinical trial NCT00098514: Talotrexin in Treating Patients With Advanced or Recurrent Solid Tumors
Official title: A Phase I Study Of PT523 In Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-12-08
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: There were 7 potential PT523 single agent dose levels to be evaluated in this phase I study
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
Study officials:
name: Joseph Paul Eder, MD
role: PRINCIPAL_INVESTIGATOR
References: