Open Label Clinical Trial of Intravenous Crotoxin

This study has suspended participant recruitment.
(Funding issues)
Sponsor:
Information provided by (Responsible Party):
Celtic Biotech Ltd
ClinicalTrials.gov Identifier:
NCT01481532
First received: October 11, 2011
Last updated: February 13, 2015
Last verified: February 2015
  Purpose

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 Intervention Phase
Cancer
Drug: Crotoxin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Further study details as provided by Celtic Biotech Ltd:

Primary Outcome Measures:
  • Tolerability of intra-patient dose escalation [ Time Frame: 54 days ] [ Designated as safety issue: Yes ]
    Assess the safety and tolerability of Crotoxin administered intravenously to Stage IV cancer patients using intra-patient dose escalation procedure.

  • Confirmation of the induction of drug tolerance [ Time Frame: 54 days ] [ Designated as safety issue: Yes ]
    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:
  • Assessment of drug efficacy [ Time Frame: 54 days ] [ Designated as safety issue: No ]
    Document any objective anti-tumour responses that occur in patients treated on this protocol.


Estimated Enrollment: 24
Study Start Date: September 2011
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
The cohort I will initially include a maximum of 12 patients with doses of 0.04 to 0.32 mg/m2. In Cohort I, each dose will be initially administered for 5 consecutive days with 2 days break during week-end. Crotoxin will be administered daily by intravenous administration over a 2-hour period by saline drip. Subjects will receive increasing doses over the course of 40 treatment days (8 dose levels). Intra patient dose escalation is mandatory. The aim of this study is to identify a MTD. MTD is defined as a dose where no toxicity is observed for 3 consecutive patients, or no more than one DLT is observed for 6 patients
Drug: Crotoxin
Intra patient dose escalation
Experimental: Cohort 2
The second cohort will include 12 patients with same doses of 0.04 to 0.32 mg/m2 in which the dose escalation speed will be faster. Subjects will receive increasing doses over the course of 27 treatment days (8 dose levels)
Drug: Crotoxin
Intra patient dose escalation

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 protocol also incorporates an active suppression of the allergic reaction by pre-treatment administration of antihistamines.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be adult patients with histologically confirmed advanced solid tumors who have progressed despite standard therapy, or for whom no standard therapy exists.
  2. Have an ambulatory PS (ECOG 0-1).
  3. Have tumour evaluation made within 28 days before study drug administration (patients with non measurable lesions according to the RECIST guidelines not previously irradiated are allowed to enter the trial).
  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 between 18 and 75 years
  7. Have normal marrow function with the following haematological parameters normal; Hb ≥10g/dl, WBC ≥4.0 x109/L, neutrophil count ≥ 2.0 x 109/L and platelets ≥100 x109 /L
  8. Have no medically significant impairment of cardiac or respiratory functions
  9. Have adequate hepatic function with Total bilirubin lower or equal to 1.5 x N and Transaminases lower or equal to 2.5 x N (lower or equal to 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. Will agree to participate in the study prior to starting with any specific study procedure, after having signed written informed consent.

Exclusion Criteria:

  1. Pregnant or planning to become pregnant
  2. 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
  3. Have pleural effusion/ ascites, cystic lesions or bone metastases, as the only assessable lesions
  4. Receiving any other experimental or anti-cancer therapy within 30 days before first study drug administration (except antalgic radiotherapy and hormonotherapy)
  5. 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
  6. Have had recent major surgery (within 21 days).
  7. Have a recent history of weight loss > 10% of current body weight.
  8. Have serious intermittent medical illnesses which would interfere with the ability of the patient to carry out the treatment program.
  9. On chronic steroid medication (> 20mg/day)
  10. Have primary or paraneoplastic myasthenia gravis
  11. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01481532

Locations
France
Hôpital Européen Georges Pompidou
Paris, France, 75908
Sponsors and Collaborators
Celtic Biotech Ltd
Investigators
Principal Investigator: Jacques Medioni, MD Hôpital Européen Georges Pompidou Paris, France
  More Information

No publications provided

Responsible Party: Celtic Biotech Ltd
ClinicalTrials.gov Identifier: NCT01481532     History of Changes
Other Study ID Numbers: CRTX01
Study First Received: October 11, 2011
Last Updated: February 13, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Celtic Biotech Ltd:
Antineoplastic agent

ClinicalTrials.gov processed this record on April 16, 2015