Open Label Clinical Trial of Intravenous Crotoxin Part 3

NCT01481532 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CRTX01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer

Keywords

Antineoplastic agent

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Assessment of drug efficacy

  112 days

Study Arms (1)

Cohort 3

EXPERIMENTAL

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

Interventions

Crotoxin DRUG

Intra patient dose escalation

Also known as: CB-24

Cohort 3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Celtic Biotech Ltd: lead
• Institut de Cancérologie de l'Ouest: collaborator

Study Sites (1)

Institut de Cancérologie de l'Ouest

Saint-Herblain, 44805, France

Location

Related Publications (3)

• 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

  BACKGROUND

• 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.

  PMID: 29696184 BACKGROUND

• 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.

  BACKGROUND

MeSH Terms

Conditions

Neoplasms

Interventions

Crotoxin

Intervention Hierarchy (Ancestors)

Crotalid Venoms; Viper Venoms; Snake Venoms; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• Mario Campone, MD, Ph.D

  INSTITUT DE CANCEROLOGIE DE L'QUEST, Saint Herblain, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dorothy Bray, Ph.D.

CONTACT

+447884005367; dorothy.bray@celticbiotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase Ic, continuation to assess accelerated dose escalation and determine MTD

Study Record Dates

• First Submitted: October 11, 2011
• First Posted: November 29, 2011
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)