A Phase I Dose Escalation Trial of PR104 Given Weekly in Subjects With Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine the side effects and best weekly dose of PR104 in patients with advanced solid tumors.

Official Title
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A Phase I, Multi-center, Open-label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR104 Given Weekly in Subjects With Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: PR104


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or more Histologically confirmed malignancy for which no effective therapy exists Measurable or evaluable disease ECOG Performance Status of 0 or 1. See Section 15.1 (ECOG performance status) for definition of ECOG Performance Status 0 and 1 Ability to read, understand and provide written informed consent If the subject is on systemic steroids, the dose of steroids must be stable for at least two weeks prior to the first dose of PR-104 Exclusion Criteria: Licensed or investigational anti-cancer therapy (including radiotherapy) within four weeks of the baseline disease assessment (within six weeks for nitrosoureas and Mitomycin C). Subjects on androgen deprivation therapy are allowed on study and may continue to receive androgen deprivation therapy while one study Prior radiotherapy to more than 25% of bone marrow; prior high-dose chemotherapy (including either myeloablative or non-myeloablative transplants); or prior receipt of more than three chemotherapy regimens Absolute neutrophil count of < 1.5 x 109/L Platelet count of < 100 x 109/L Hemoglobin level of < 90 g/L (or requiring a red blood cell transfusion to maintain hemoglobin > 90 g/L) Serum bilirubin greater than the upper limit of normal ALT and AST greater than 2.5 times the upper limit of normal Serum creatinine less than 1.5 times upper limit of normal Prothrombin time (PT-INR) or activated partial thromboplastin time (APTT) greater than 1.1 times the upper limit of normal range Women who are pregnant, breast-feeding or planning to become pregnant during the study Men or women of reproductive-potential who are unwilling to use an effective method of contraception during the study and for 30 days following the last dose of study medication. See section 5.11 (Contraceptives) for definition of effective methods of contraception Evidence of any other significant medical disorder or laboratory finding that in the opinion of the Investigator compromises the subject's safety during study participation, including uncontrolled infection or infection requiring a concomitant parenteral antibiotic Plans for concomitant anti-cancer therapy (excluding androgen deprivation therapy) while on study Less than four weeks since major surgery Known to be HIV positive, Hepatitis B sAg positive or Hepatitis C positive with abnormal liver function tests No known contraindication to single doses of naproxen

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PR104<br> | Drug: PR104<br>* Dose escalation of PR104 to determine maximum tolerated dose for weekly administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose (MTD) of PR104 when administered weekly | MTD is based on cycle 1 data and defined as the maximum dose that can be administered to 6 subjects with no more than one of the following DLTs: Grade 4 thrombocytopenia Grade 4 heme toxicity (excluding thrombocytopenia) that lasts for ≥ 5 days (Neutrophils < 500/mm3, ANC ≤ 0.5 K/mm3, lymphocytes < 1K/mm3, HGB < 6.5 gm/dL) Non-heme toxicity ≥ Grade 3 despite appropriate treatment Neutropenic fever Grade 2 or higher neurotoxicity of ≥ 1 week Any toxicity of Grade 2 or higher that has not resolved within 2 weeks of end of cycle 1 (except grade 2 alopecia) | 4 weeks (cycle 1) |