A Study of rSIFN-co in Subjects With Advanced Solid Tumors (rSIFN-01)

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung Read More

Inclusion Criteria:

1. a) Histologically confirmed diagnosis of advanced solid tumors that is metastatic or unresectable and for which standard therapies (according to local practice) or palliative measures do not exist or subject decides not to receive any available treatment (dose escalation cohort) OR

   b) Histologically or Cytologically diagnosis of Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Melanoma, Hepatocellular Carcinoma* and Colon Cancer metastatic or unrespectable and for which standard therapies (according to local practice) or palliative measures do not exist or subject decides not to receive any available treatment (dose expansion cohort) (dose expansion cohort)

   * Hepatocellular Carcinoma patients may be enrolled based on radiological diagnosis instead of histological or cytological diagnosis - based on "EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma (Journal of Hepatology 56:908-943, 2012), non-invasive hepatocellular carcinoma patients should not be put under additional undue risk of liver biopsy after the diagnosis of hepatocellular carcinoma has been ascertained with clinical, laboratory and radiographic evaluation."

2. Measurable disease is preferred but not mandatory for the purpose of study accrual. Evaluable disease is sufficient.
3. Age > or = 21 years
4. ECOG performance status < or = 2

5. Adequate laboratory values at the time of screening:

   (For both dose escalation and expansion)

   • leukocytes ≥3,000/mcL
   • absolute neutrophil count ≥1,500/mcL
   • platelets ≥100,000/mcL
   • haemoglobin ≥9.0 g/DL

   (Dose escalation only)

   • total bilirubin ≤ the upper limits of normal (ULN)
   • AST(SGOT)/ALT(SGPT) ≤ the upper limits of normal (ULN)
   • creatinine < the upper limits of normal (ULN) OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal

   (Dose expansion only)

   • total bilirubin ≤ 1.5 times the upper limits of normal (ULN)
   • AST(SGOT)/ALT(SGPT) ≤ 2.5 times the upper limits of normal (ULN) or ≤ 4 times upper limits of normal (ULN) for patients with liver metastasis
   • creatinine ≤1.5 times the upper limits of normal (ULN) OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels above 1.5 times the institutional upper limits of normal

   (For renal cell carcinoma patients)

   • creatinine ≤ 1.5 times the upper limits of normal (ULN) OR creatinine clearance ≥ 40 mL/min/1.73 m2 for subjects with creatinine levels above 1.5 times the institutional upper limits of normal.
6. Life expectancy > 3 months
7. Agreement to be compliant to visit schedules as defined in the protocol.
8. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
9. The effects of rSIFN-co on the developing human fetus are unknown. For this reason women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of r-SIFN-co administration. WOCBP must have a negative urine pregnancy test at Visit 1 (Screening).

Exclusion Criteria:

1. Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to start of rSIFN-co administration or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
2. Subjects receiving other investigational drugs within 5 times the half-life of the investigational drugs or within 4 weeks, prior to start of rSIFN-co administration.
3. Subject must not have known untreated brain or meningeal metastases. CT scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease. Subjects with treated brain metastases that are radiographically or clinically stable for at least 4 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion(s) are eligible, provided that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 4 weeks prior to start of rSIFN-co administration).
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to interferon.
5. Uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial pneumonia or psychiatric illness/social situations that would limit compliance with study requirements.
6. HIV-positive subjects on combination antiretroviral therapy are ineligible because of the increased risk of lethal infections when treated with immunomodulatory therapy. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated.
7. The investigator or sub-investigator considers the subject's physique as inappropriate for investigational product treatment or any other reason(s) that may render the subjects inappropriate for participation in the trial.
8. Subjects who may have autoimmune disorders, decompensated liver diseases or life-threatening neurologic diseases.