Open Label Clinical Trial of Intravenous Crotoxin Part 3

NCT ID: NCT01481532

Last Updated: 2024-01-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-31
• Study Completion Date: 2025-12-31

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.

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.

Conditions

Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Crotoxin

Intervention Type: DRUG

Intra patient dose escalation

Interventions

Crotoxin

Intra patient dose escalation

Intervention Type: DRUG

Other Intervention Names

CB-24

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut de Cancérologie de l'Ouest

UNKNOWN

Sponsor Role: collaborator

Celtic Biotech Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mario Campone, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Institut de Cancérologie de l'Ouest

Saint-Herblain, , France

Countries

France

Central Contacts

Dorothy Bray, Ph.D.

Role: CONTACT

dorothy.bray@celticbiotech.com

+447884005367

References

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.

Reference Type: BACKGROUND

PMID: 29696184 (View on PubMed)

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.

Reference Type: BACKGROUND

Other Identifiers

CRTX01

Identifier Type: -

Identifier Source: org_study_id