A Phase I, Open-Label, Multicenter, Dose Escalation Study to Assess the Safety and Tolerability of Genz-644282 in Patients With Advanced Malignant Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Genz-644282 (28-day dosing schedule)
- Conditions
- Solid Tumors
- Sponsor
- Genzyme, a Sanofi Company
- Enrollment
- 87
- Locations
- 4
- Primary Endpoint
- Determine the Maximum Tolerated Doses for the 28-day and 21-day dosing schedules
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
This is a Phase I, open-label, multicenter, dose-escalation study designed to assess the safety and tolerability of Genz-644282, administered as an intravenous (IV) infusion, to patients with advanced malignant solid tumors. Each 28 day cycle of treatment will consist of 3 consecutive weeks of treatment every 28 days(i.e., treatment will be administered on Days 1, 8, and 15 every 28 days). Each 21 day cycle of treatment will consist of 2 consecutive weeks of treatment every 21 days(i.e., treatment will be administered on Days 1 and 8 every 21 days). Treatment with Genz-644282 will continue until disease progression or unacceptable toxicity is observed. Approximately 110 patients will be enrolled in this study. Patients will be enrolled in escalating dose cohorts until the Maximum Tolerated Doses (MTDs) for the 2 dosing schedules are established. To further evaluate safety, approximately 40 additional patients with advanced malignant solid tumors will be enrolled and treated at the MTDs (20 for each dosing schedule) during an expansion phase.
Detailed Description
This is a Phase I, open-label, multicenter, dose-escalation study designed to assess the safety and tolerability of Genz-644282, administered as an IV infusion, to patients with advanced malignant solid tumors. Drug will be administered as a 60-minute IV infusion on days 1, 8, and 15 of the 28 day treatment cycle, or on days 1 and 8 of the 21 day treatment cycle. Treatment with Genz-644282 will continue until disease progression or unacceptable toxicity is observed. Patients will be enrolled in escalating dose cohorts until the Maximum Tolerated Doses (MTDs) are established. Safety will be evaluated throughout the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consent
- •Patients enrolled in dose-escalation phase: Histologically or cytologically confirmed advanced malignant solid tumor for which no standard therapeutic option exists.
- •For the disease indications evaluated in the expansion phase, the following criteria must be met:
- •Have one of the following histologically or cytologically confirmed advanced malignant solid tumors for which no standard therapeutic option exists:
- •Colorectal cancer (prior systemic regimen must have included ≥1 of the following: fluoropyrimidine or oxaliplatin);
- •Squamous Non-small cell lung cancer or small cell lung cancer (prior systemic regimen must have included ≥1 of the following: cis-platinum or carbo platinum);
- •Pancreatic cancer (prior systemic regimen must have included gemcitabine);
- •Breast cancer (prior systemic regimen must have included ≥1 of the following: taxane, anthracycline, or fluoropyrimidine)
- •Received no more than 4 prior systemic therapy regimens for their malignancy
- •Experienced progression or intolerance to their immediate prior systemic therapy regimen.
Exclusion Criteria
- •Received previous treatment with or have a known hypersensitivity to Genz-644282 or to any of its components.
- •Received radiotherapy to the only site of measurable disease, unless the tumor at this site continues to increase in size after the patient has completed radiotherapy treatment.
- •Used any investigational agent, other than anti-cancer chemotherapy, during the 4 weeks prior to the first dose of Genz-
- •Have psychiatric disorder(s) that would interfere with consent, study participation, or follow up (with the possible exception of incompetence as defined by New Jersey for the purposes of participation in clinical trials in the state of New Jersey).
- •Have uncontrolled congestive heart failure or angina, a history of myocardial infarction within 6 months prior to study enrollment, or a cardiac functional capacity Class III or IV, as defined by the New York Heart Association Classification.
- •Have a resting QT with Bazett's correction (QTcB) interval of \> 460 msec, calculated as the average of at least 2 of the longest QT intervals measured on 12-lead recordings made prior to dosing with Genz-
- •Have a systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement) despite appropriate antibiotics or other treatment.
- •Have any other severe concurrent disease or a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo chemotherapy.
- •A known diagnosis of human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS) or viral hepatitis B or C.
- •Presence of ≥ Grade 2 peripheral neuropathy.
Arms & Interventions
Study Drug: Genz-644282 (28-day dosing schedule)
Genz-644282 (Each cohort will be based on dose-escalation)
Intervention: Genz-644282 (28-day dosing schedule)
Study Drug: Genz-644282 (21-day dosing schedule)
Genz-644282 (Each cohort will be based on dose-escalation)
Intervention: Genz-644282 (21-day dosing schedule)
Outcomes
Primary Outcomes
Determine the Maximum Tolerated Doses for the 28-day and 21-day dosing schedules
Time Frame: 24 Months
Secondary Outcomes
- Establish the pharmacokinetic (PK) profile through calculation of area under the curve of blood and urine concentrations.(36 Months)
- Pharmacokinetics (PK) as measured by maximal observed concentration (Cmax)(36 months)
- Pharmacokinetics (PK) as measured by the amount and fraction of drug excreted in urine(36 months)
- Assess evidence of antitumor activity(36 months)
- Evaluate ongoing benefit as determined by the investigator and defined as an improvement in performance status(36 months)
- Pharmacokinetics (PK) as measured by time to maximal observed concentration (Tmax)(36 months)
- Pharmacokinetics (PK) as measured by half-life (T1/2)(36 months)
- Determine the recommended Phase 2 doses for the 28-day and 21-day dosing schedules(36 Months)