Safety Study of GPX-150 in Patients With Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors - Phase 1 Population
• Intervention / Treatment: Drug: GPX-150 for Injection

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GPX-150 for Injection; GPX-150 is administered IV on Day 1, followed by a 20 day rest period, every 3 weeks.	Drug: GPX-150 for Injection; 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.; Other Names: GPX-150; 5-imino-13-deoxy-doxorubicin HCl

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Gem Pharmaceuticals
• Investigators: Principal Investigator: Raymond J Hohl, MD, PhD, University of Iowa

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: July 2, 2008
• First Submitted That Met QC Criteria: July 3, 2008
• First Posted (Estimate): July 4, 2008

Study Record Updates

• Last Update Posted (Estimate): August 5, 2014
• Last Update Submitted That Met QC Criteria: August 4, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: GPX-150-001