Talotrexin in Treating Patients With Advanced or Recurrent Solid Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase I Study Of PT523 In Patients With Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: talotrexin ammonium


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: There were 7 potential PT523 single agent dose levels to be evaluated in this phase I study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1a<br>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<br> <br> |
| Experimental: Dose Level 1b<br>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<br> <br> |
| Experimental: Dose Level 1c<br>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<br> <br> |
| Experimental: Dose Level 2<br>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<br> <br> |
| Experimental: Dose Level 3<br>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<br> <br> |
| Experimental: Dose Level 4<br>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<br> <br> |
| Experimental: Dose Level 5<br>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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific