This trial is active, not recruiting.

Condition cancer
Treatment crotoxin
Phase phase 1
Sponsor Celtic Biotech Ltd
Collaborator Immunoclin
Start date September 2011
End date December 2016
Trial size 24 participants
Trial identifier NCT01481532, CRTX01


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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
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

Primary Outcomes

Tolerability of intra-patient dose escalation
time frame: 54 days
Confirmation of the induction of drug tolerance
time frame: 54 days

Secondary Outcomes

Assessment of drug efficacy
time frame: 54 days

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria: 1. Be adult patients with histologically confirmed advanced solid tumors who have progressed despite standard therapy, or for whom no standard therapy exists. 2. Have an ambulatory PS (ECOG 0-1). 3. Have tumour evaluation made within 28 days before study drug administration (patients with non measurable lesions according to the RECIST guidelines not previously irradiated are allowed to enter the trial). 4. Have completed radiotherapy or chemotherapy or any other anticancer therapy (including experimental therapy) more than 4 weeks prior to enrolment into the trial and must have recovered from all acute side effects of these treatments 5. Have a life expectancy greater than 3 months 6. Have an age between 18 and 75 years 7. Have normal marrow function with the following haematological parameters normal; Hb ≥10g/dl, WBC ≥4.0 x109/L, neutrophil count ≥ 2.0 x 109/L and platelets ≥100 x109 /L 8. Have no medically significant impairment of cardiac or respiratory functions 9. Have adequate hepatic function with Total bilirubin lower or equal to 1.5 x N and Transaminases lower or equal to 2.5 x N (lower or equal to 5 x N in case of liver metastasis). 10. Have no history of prior severe allergic reactions to venoms 11. Have Creatinine clearance ≥ 50 mL/min. 12. Be on stable doses of any drugs which may affect hepatic drug metabolism or renal drug excretion (e.g.--non-steroidal anti-inflammatory drugs, barbiturates, narcotic analgesics, probenecid). Such drugs should not be initiated while the patient is participating in this study. 13. Will agree to participate in the study prior to starting with any specific study procedure, after having signed written informed consent. Exclusion Criteria: 1. Pregnant or planning to become pregnant 2. Known to have brain metastases or leptomeningeal involvement. CT-scan or MRI is not required to rule this out unless there is clinical suspicion of central nervous system involvement 3. Have pleural effusion/ ascites, cystic lesions or bone metastases, as the only assessable lesions 4. Receiving any other experimental or anti-cancer therapy within 30 days before first study drug administration (except antalgic radiotherapy and hormonotherapy) 5. Have a history of other malignancies, except for patients with a cancer free interval of > 5 years after treatment completion, patients with prior history of adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix 6. Have had recent major surgery (within 21 days). 7. Have a recent history of weight loss > 10% of current body weight. 8. Have serious intermittent medical illnesses which would interfere with the ability of the patient to carry out the treatment program. 9. On chronic steroid medication (> 20mg/day) 10. Have primary or paraneoplastic myasthenia gravis 11. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Additional Information

Official title Open Label Phase I Clinical Trial of Crotoxin in Patients With Advanced Cancer Using an Intravenous Route of Administration
Principal investigator Jacques Medioni, MD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Celtic Biotech Ltd.