Open Label Clinical Trial of Intravenous Crotoxin
The primary objective of the study is to assess whether human subjects can be made tolerant to intravenously administered Crotoxin and achieve higher and more therapeutically effective doses levels without the previously reported adverse effects associated with bolus i.m. administration.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open Label Phase I Clinical Trial of Crotoxin in Patients With Advanced Cancer Using an Intravenous Route of Administration|
- Tolerability of intra-patient dose escalation [ Time Frame: 54 days ] [ Designated as safety issue: Yes ]Assess the safety and tolerability of Crotoxin administered intravenously to Stage IV cancer patients using intra-patient dose escalation procedure.
- Confirmation of the induction of drug tolerance [ Time Frame: 54 days ] [ Designated as safety issue: Yes ]Confirm in a controlled phase I trial that human subjects can be made tolerant to intravenously administered Crotoxin thereby reducing the potential for adverse drug effects
- Assessment of drug efficacy [ Time Frame: 54 days ] [ Designated as safety issue: No ]Document any objective anti-tumour responses that occur in patients treated on this protocol.
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||January 2017|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
Experimental: Cohort 1
The cohort I will initially include a maximum of 12 patients with doses of 0.04 to 0.32 mg/m2. In Cohort I, each dose will be initially administered for 5 consecutive days with 2 days break during week-end. Crotoxin will be administered daily by intravenous administration over a 2-hour period by saline drip. Subjects will receive increasing doses over the course of 40 treatment days (8 dose levels). Intra patient dose escalation is mandatory. The aim of this study is to identify a MTD. MTD is defined as a dose where no toxicity is observed for 3 consecutive patients, or no more than one DLT is observed for 6 patients
Intra patient dose escalation
Experimental: Cohort 2
The second cohort will include 12 patients with same doses of 0.04 to 0.32 mg/m2 in which the dose escalation speed will be faster. Subjects will receive increasing doses over the course of 27 treatment days (8 dose levels)
Intra patient dose escalation
Crotoxin has been shown to induce neurotoxic tolerance in animals allowing them to receive high doses associated with effective anti-tumor activity in the absence of adverse side effects.
The study plans to demonstrate this effect in human subjects using two dose escalation protocols; slow and fast. It is believed that this approach will prevent toxic side effects to subjects.
The route of administration has not been employed clinically and is designed to avoid the myonecrotic effects of intramuscular injections. The target maximum dose is almost double that off the previously reported MTD.
The protocol also incorporates an active suppression of the allergic reaction by pre-treatment administration of antihistamines.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01481532
|Hôpital Européen Georges Pompidou|
|Paris, France, 75908|
|Principal Investigator:||Jacques Medioni, MD||Hôpital Européen Georges Pompidou Paris, France|