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Open Label Clinical Trial of Intravenous Crotoxin

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ClinicalTrials.gov Identifier: NCT01481532
Recruitment Status : Recruiting
First Posted : November 29, 2011
Last Update Posted : February 2, 2018
Immunoclin Ltd
Information provided by (Responsible Party):
Celtic Biotech Ltd

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cancer Drug: Crotoxin Phase 1

Detailed 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 revised protocol incorporates continuous infusion with a mobile pump and includes active suppression of the allergic reaction by pre-treatment administration of antihistamines.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (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
Anticipated Study Start Date : February 2018
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : February 2019

Arm Intervention/treatment
Experimental: Cohort 3
The third cohort will include up to 18 patients with Crotoxin doses of 0.12 to 1.16 mg per m2 in which the dose escalation speed will be faster. Drug is administered over 48 hour intervals using ambulatory infusion pumps; treating on an outpatient basis. Subjects will receive increasing doses over the course of 35 treatment days (15 dose levels).
Drug: Crotoxin
Intra patient dose escalation
Other Name: antihistamine

Primary Outcome Measures :
  1. Tolerability of intra-patient dose escalation [ Time Frame: 35 days ]
    Assess the safety and tolerability of Crotoxin administered intravenously to Stage IV cancer patients using intra-patient dose escalation procedure.

  2. Confirmation of the induction of drug tolerance [ Time Frame: 35 days ]
    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

Secondary Outcome Measures :
  1. Assessment of drug efficacy [ Time Frame: 35 days ]
    Document any objective anti-tumour responses that occur in patients treated on this protocol.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Subjects will:

  1. Be adult patients with histologically confirmed advanced solid tumors (excluding basal cell, colon, pancreatic and stomach cancers) who have progressed despite standard therapy, or for whom no standard therapy exists.
  2. Have an ambulatory PS (ECOG 0-1).
  3. Have tumor evaluation made within 28 days before study drug administration
  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 ≥ 18 years
  7. Have normal marrow function with the following haematological parameters normal; Hb ≥10g/dl, WBC ≥4.0 x10E9/L, neutrophil count ≥ 2.0 x 10E9/L and platelets ≥100 x10E9 /L
  8. Have no medically significant impairment of cardiac or respiratory functions<
  9. Have adequate hepatic function with Total bilirubin 1.5 x N and Transaminases < 2.5 x N (< 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. Not be pregnant or planning to become pregnant
  14. Not 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
  15. Not have pleural effusion/ ascites, cystic lesions or bone metastases, as the only assessable lesions
  16. Not 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
  17. Not have had recent major surgery (within 21 days).
  18. Not have a recent history of weight loss > 10% of current body weight.
  19. Not have serious intermittent medical illnesses which would interfere with the ability of the patient to carry out the treatment program.
  20. Not be on chronic steroid medication (> 20mg/day)
  21. Not have primary or paraneoplastic myasthenia gravis
  22. Be free of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
  23. Will agree to participate in the study prior to starting with any specific study procedure, after having signed written informed consent.
  24. Be patients of childbearing age willing to use contraceptive for the duration of the study
  25. Not live alone and live no further than approximately 30 km away from the hospital, and for the study duration have continuous access to the use of mobile telephone in case of medical emergency

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01481532

Contact: Dorothy Bray, Ph.D. +447884005367 dorothy.bray@immunoclin.com

Salpetriere Hospital Recruiting
Paris, France, 75013
Contact: Maria A Gil-Delgado, MD    +33 1 42 16 05 08    marian-gil-delgado@psl.aphp.fr   
Principal Investigator: Maria A Gil-Delgado, MD         
Sponsors and Collaborators
Celtic Biotech Ltd
Immunoclin Ltd
Principal Investigator: Maria A Gil-Delgado, MD, Ph.D Salpetriere Hospital, Paris, France

Medioni J, Brizard M, Elaidi R, Reid PF, Benlhassan K, Bray D. Innovative design for a phase 1 trial with intra-patient dose escalation: The Crotoxin study. Contemp Clin Trials Commun 7:186-188, 2017

Responsible Party: Celtic Biotech Ltd
ClinicalTrials.gov Identifier: NCT01481532     History of Changes
Other Study ID Numbers: CRTX01
First Posted: November 29, 2011    Key Record Dates
Last Update Posted: February 2, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Celtic Biotech Ltd:
Antineoplastic agent