Safety Study of GPX-150 in Patients With Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1 safety and dose escalation study to define the maximum tolerated dose (MTD) and identify the dose limiting toxicities (DLT) following IV administration of GPX-150 once every 3 weeks. Escalating doses starting at the dose of 14 mg/m2 and increasing to the dose of 265 mg/m2 will be administered IV once every 3 weeks for up to 8 cycles of treatment. Patients who have previously received an anthracycline are limited to 4 cycles of treatment.

Official Title
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Phase 1 Study and Dose Seeking Study of an Intravenous Formulation of the Anthracycline Analog GPX-150 in Patients With Solid Tumors

Conditions
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Advanced Solid Tumors - Phase 1 Population

Intervention / Treatment
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* Drug: GPX-150 for Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is at least 18 years of age. Patient has a histologically or cytologically confirmed diagnosis of solid tumor. Patient has progressive disease Patient is considered to have incurable disease and is not a candidate for known effective systemic treatment. Patient has a performance status of at least 70% on Karnofsky scale. Patient has not received any cytotoxic chemotherapy or other investigational agents within 4 weeks of the first treatment in this study (6 weeks for mitomycin or nitrosourea). Patients should receive supportive care as indicated. Patients currently receiving blood transfusions or erythropoiesis-stimulating agents should continue receiving them as per the ASCO guidelines. Patients requiring palliative radiation therapy should complete their course of radiation treatment 4 weeks before the first study treatment. Patient may have received unlimited prior hormonal therapy, but this must have been completed at least 4 weeks prior to the first study treatment, and progressive disease documented following withdrawal of hormone therapy. Patient with hormone-refractory prostate cancer on long acting LHRH agents may continue on these agents. Patient may have received unlimited prior biological or immunological therapy without limitation, but this must have been completed at least 4 weeks prior to the first study treatment. Patient has fully recovered from any previous surgery (at least 4 weeks since major surgery) and radiation therapy (at least 4 weeks since the end of treatment). Patient has recovered from reversible toxicity of prior therapy. Permanent and stable side effects or changes are acceptable if ≤ to Grade 2. Patient has adequate hematological function as defined by an ANC ≥ 1500, platelets ≥ 100,000/µL, and hemoglobin ≥9.0 gm/dL. Patient has adequate organ function defined as a bilirubin ≤ 1.5 times ULN, AST and ALT < 2.5 times the upper limit of normal (ULN, 5.0 times the ULN with liver involvement), serum creatinine <2.0 dL or estimated creatinine clearance ≥ 50 ml/min. Patient has an ejection fraction of 110% of the lower limit of institutional normal as determined by resting MUGA scan. Patient has an O2 Sat by pulse oximetry of at least 90%. Patient has a negative pregnancy test prior to study entry if premenopausal or if less than 12 months after menopause. Premenopausal patients must use a medically effective form of contraception during the treatment period. Patient is willing and able to comply with all study protocol requirements. The patient or a legally authorized representative must fully understand all elements of the informed consent and have signed the informed consent according to institutional and federal regulatory requirements. Exclusion Criteria: Patient is pregnant or breast-feeding. Patient has a history of hypersensitivity to anthracyclines. Patient has received a cumulative dose of doxorubicin that exceeds 300 mg/m2 or a cumulative dose of epirubicin that exceeds 540 mg/m2. Patient has received an anthracycline within 6 months prior to entry into the study. Patient has brain metastases unless asymptomatic and stable off glucocorticoids. Prior history of CHF, myocardial infarction within 6 months prior to enrollment, active ischemic heart disease, or uncontrolled hypertension. Patient requires active medical therapy for CHF or arrhythmia. Patients with > Grade l motor neuropathy or > Grade 2 sensory neuropathy. Patient has participated in a study of any investigational drug within 4 weeks prior to the first study treatment. Patient has received chemotherapy, hormonal therapy (with the exception of LHRH for prostate cancer), immunotherapy, biological therapy, or radiotherapy within 4 weeks prior to the first study treatment. Patient has had major surgery within 4 weeks of the first study treatment. Patient has received G-CSF or GM-CSF within 4 weeks prior to first dose of study drug. Patient has baseline laboratory values that are outside normal ranges or those listed (see Inclusion Criteria), which are clinically significant as determined by the investigator. Patient has a serious, concurrent medical condition that would limit the patient's ability to complete or comply with the study requirements. Patient is unable or unwilling to comply with the contraceptive requirements during the study period. Patient has lymphoma.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GPX-150 for Injection<br>GPX-150 is administered IV on Day 1, followed by a 20 day rest period, every 3 weeks. | Drug: GPX-150 for Injection<br>* Escalating doses starting at the dose of 14 mg/m2 and increasing to the dose of 265 mg/m2 will be administered IV once every 3 weeks for up to 8 cycles of treatment. Patients who have previously received an anthracycline are limited to 4 cycles of treatment.<br>* Other names: 5-imino-13-deoxy-doxorubicin HCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define maximum tolerated dose and identify dose limiting toxicities following IV administration of GPX-150 for Injection once every 3 weeks |  | Every 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics and any antitumor activity |  | Every 3 weeks |