Open Label Clinical Trial of Intravenous Crotoxin Part 3

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01481532
• Other study ID #: CRTX01
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: August 2024
• Est. completion date: December 2025

Study information

• Verified date: January 2024
• Source: Celtic Biotech Ltd
• Contact: Dorothy Bray, Ph.D.
• Phone: +447884005367
• Email: dorothy.bray[@]celticbiotech.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: December 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• Crotoxin
Intra patient dose escalation

Locations

Country	Name	City	State
France	Institut de Cancérologie de l'Ouest	Saint-Herblain

Sponsors (2)

Lead Sponsor	Collaborator
Celtic Biotech Ltd	Institut de Cancérologie de l'Ouest

Country where clinical trial is conducted

France, 

References & Publications (2)

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.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Assessment of drug efficacy	Document any objective anti-tumour responses that occur in patients treated on this protocol.	112 days