Open Label Phase I Clinical Trial of Crotoxin in Patients With Advanced Cancer Using an Intravenous Route of Administration
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
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
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.
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
3. Have pleural effusion/ ascites, cystic lesions or bone metastases, as the only
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