Combination Therapy of F16IL2 and Paclitaxel in Solid Tumour Patients

Inclusion Criteria

• •For Phase I, cohorts 1 to 8, of the study:
• •For patient of Phase I cohort 1, i.e. those patients receiving F16IL2 alone, patients must not be amenable to therapy with paclitaxel/taxanes but must be considered by the Principal Investigator to be suitable candidates for F16IL2 therapy alone.
• •Histologically or cytologically confirmed solid cancer with/without evidence of locally advanced or metastatic disease.
• •For advanced solid cancer patients, patients may have received previous chemotherapy or radiation therapy, but they must be amenable for paclitaxel treatment according to the discretion of the principal investigator.
• •For Phase I, cohorts 9 onwards:
• •Histologically or cytologically confirmed bladder cancer, breast cancer, unresectable metastatic (stage IV) non-uveal melanoma, mesothelioma, NSCLC, prostate cancer or sarcoma.
• •Prior therapies for metastatic disease are allowed, but patients must be amenable for paclitaxel treatment according to the discretion of the principal investigator.
• •For breast cancer patients only: patients not suitable for trastuzumab therapy (i.e., no evidence of HER2-overexpressing disease, or trastuzumab therapy exhausted in HER2-overexpressing disease).
• •For Phase II of the study:
• •Histologically or cytologically confirmed breast cancer, unresectable metastatic (stage IV) non-uveal melanoma, or NSCLC.
• •Prior therapies for metastatic disease are allowed, but patients must be amenable for paclitaxel treatment according to the discretion of the principal investigator.
• •For breast cancer patients only: patients not suitable for trastuzumab therapy (i.e., no evidence of HER2-overexpressing disease, or trastuzumab therapy exhausted in HER2-overexpressing disease).
• •For phase I and II of the study:
• •Patients aged ≥ 18 years.
• •Prior radiation therapy is allowed, if the irradiated area is not the only source of measurable or assessable disease.
• •ECOG performance status ≤ 2
• •Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria (see Section APPENDIX A). This lesion must not have been irradiated during previous treatments.
• •All acute toxic effects (excluding alopecia) of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v3.0) Grade ≤ 1.
• •Sufficient hematologic, liver and renal function:
• •* Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, platelets ≥ 100 x 10\^9/L, haemoglobin (Hb) ≥ 9.5 g/dl.
• •* Alkaline phosphatase (AP), alanine aminotransferase (ALT) and or aspartate aminotransferase ≤ 3 x upper limit of reference range (ULN), and total bilirubin ≤ 2.0 mg/gL unless liver involvement by the tumor, in which case the transaminase levels could be up to 5 x ULN.
• •* Creatinine ≤ 1.5 ULN or 24 h creatinine clearance ≥ 50 mL/min.
• •Life expectancy of at least 12 weeks.
• •Documented negative test for human immunodeficiency virus.
• •Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment.
• •If of childbearing potential, agreement to use adequate contraceptive methods (e.g., oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug.
• •Evidence of a personally signed and dated Ethics Committee-approved Informed Consent form indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study.
• •Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.