Open Label Clinical Trial of Intravenous Crotoxin Part 3

Open Label Phase I Clinical Trial of Crotoxin in Patients With Advanced Cancer Using an Intravenous Route of Administration

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 Overview

• Status: Not yet recruiting
• Conditions: Cancer
• Intervention / Treatment: Drug: Crotoxin

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 five times that of 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
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Dorothy Bray, Ph.D.; Phone Number: +447884005367; Email: dorothy.bray@celticbiotech.com

Study Locations

• France
  • Saint-Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: Cohort 3; The third cohort will include up to 24 patients with Crotoxin doses of 0.2 to 1.32 mg per m2 in which the dose escalation speed will be faster. Drug is administered over 3 + 4 day intervals using ambulatory infusion pumps; treating on an outpatient basis. Subjects will receive increasing doses over the course of 28 treatment days (8 dose levels). Dose escalation will continue if DLT is not established

Drug: Crotoxin; Intra patient dose escalation; Other Names: CB-24

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of intra-patient dose escalation	Assess the safety and tolerability of Crotoxin administered intravenously to Stage IV cancer patients using intra-patient dose escalation procedure.	28 days
Confirmation of the induction of drug tolerance	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	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of drug efficacy	Document any objective anti-tumour responses that occur in patients treated on this protocol.	112 days

Collaborators and Investigators

• Sponsor: Celtic Biotech Ltd
• Collaborators: Institut de Cancérologie de l'Ouest
• Investigators: Principal Investigator: Mario Campone, MD, Ph.D, INSTITUT DE CANCEROLOGIE DE L'QUEST, Saint Herblain, France

Publications and helpful links

General Publications

• 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. 2017 Jul 23;7:186-188. doi: 10.1016/j.conctc.2017.07.008. eCollection 2017 Sep.
• Gil-Delgado M, Paul G, Bray DH, Delgado F, Spano JP, Idbaih A, Reid PF, Benlhassan K, Diaw C, Khayat D. Continuous i.v. Crotoxin in advanced cancer: Intra-patient dose escalation. Cancer Res (2018) 78 (13_Supplement): CT071.
• Delgado MG, Gougis P, Bray DH, Delgado FM, Spano JP, Idbaih A, Reid PF, Benlhassan K, Diaw C, Khayat D. Abstract CT071: Continuous i.v. Crotoxin in advanced cancer: Intra-patient dose escalation. Cancer Res (2018) 78 (13_Supplement): CT071. https://doi.org/10.1158/1538-7445.AM2018-CT071

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: October 11, 2011
• First Submitted That Met QC Criteria: November 28, 2011
• First Posted (Estimated): November 29, 2011

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 12, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Antineoplastic agent
• Additional Relevant MeSH Terms: Neoplasms; Biological Factors; Complex Mixtures; Toxins, Biological; Venoms; Crotalid Venoms; Viper Venoms; Snake Venoms; Crotoxin
• Other Study ID Numbers: CRTX01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No