A Phase I, Dose-Escalating, Safety Study of an Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PL-MLP, PROMITIL) in Cancer Patients With Solid Tumors.
1. Patients diagnosed with inoperable, recurrent or metastatic malignant solid tumors,
deemed incurable, and who have either:
- Failed to respond to standard therapy or
- For whom no standard therapy is available or
- Refuse to receive standard therapies
2. Histologically or cytologically confirmed diagnosis of solid tumor on file.
3. Age 18-80 years
4. BMI: 18-36
5. ECOG Performance Status ≤ 2
6. Estimated life expectancy of at least 3 months
7. Adequate bone marrow function (an absolute neutrophil count ≥1500/mm3, hemoglobin
≥9.5 g/dl, HgbA1C≤7%, and a platelet count ≥100,000/mm3(
8. Adequate liver function (serum bilirubin ≤2.0 mg/100 ml; alanine aminotransferase ≤2×
9. Adequate renal function (serum creatinine ≤1.5 mg/100 ml or creatinine clearance ≥45
10. No prior intravenous treatment with Mitomycin-C either alone or in combination
11. No other myelosuppressive treatment within 4 weeks before start of the study drug.
12. No other anti-cancer treatment within 2 weeks before start of the study drug
13. No prior extensive radiotherapy (e.g., whole pelvis or craniospinal) or bone marrow
transplantation with total body irradiation.
14. Women of child bearing potential practicing an acceptable method of birth control.
15. Understanding of study procedures and willingness to comply for the entire length of
the study and to give written informed consent
1. Known hypersensitivity to the study drug or to any of its components
2. CHF (NYHA = Class IV) or LVEF≤40%
3. COPD > Stage 3 (FEV1<50%, FEV1/FVC<70%);
4. CKF >Stage 4 (patients with known GFR<30mL/min/1.73m2);
5. Cirrhosis (Child-Pugh Class C score);
6. Any other severe concurrent disease which in the judgment of the investigator would
make the subject inappropriate for entry into this study
7. History of human immunodeficiency virus (HIV) infection
8. History of chronic active hepatitis including subjects who are carriers of hepatitis
B virus (HBV) or hepatitis C virus (HCV).
9. Presence of uncontrolled infection.
10. Evidence of active bleeding or bleeding diathesis
11. Brain metastases in symptomatic patients requiring ≥4 mg dexametasone/day. However,
patients with treated brain metastases by surgery or radiation who are stable and
symptom-free (<4 mg dexametasone/day) for a minimum period of 4 weeks post-treatment
12. Pregnant or lactating
13. Treatment with other investigational drugs within 14 days of start of the study drug
for non-myelosuppressive agents, and within 28 days of start of the study drug for