Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM060184 in Combination With Gemcitabine in Selected Patients With Advanced Solid Tumors

Inclusion Criteria

• •1. Voluntarily signed and dated written informed consent prior to any specific study procedure.
• •2. Age ≥ 18 years.
• •3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1 (see APPENDIX 1).
• •4. Life expectancy ≥ 3 months.
• •5. Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors that progressed to standard therapy or for whom no standard therapy exists:
• •* Breast cancer non-candidate for hormone therapy alone.
• •* Epithelial ovarian cancer (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas).
• •* Locally advanced or metastatic head and neck cancer.
• •* Non-small cell lung cancer (NSCLC).
• •* Germ cell tumors (GCTs).
• •* Biliary tract adenocarcinoma.
• •* Adenocarcinoma or carcinoma of unknown primary site (UKPS).
• •* Cervix carcinoma.
• •* Gastrointestinal stromal tumor (GIST).
• •* Urothelial cancer.
• •6. Expansion cohort at the RD:
• •All patients must have:
• •* Measurable disease according to RECIST v.1.1 (or Choi criteria and/or EORTC metabolic response criteria for solid tumors, in the case of GIST); or
• •* Evaluable disease by serum markers in the case of ovarian cancer \[Gynecologic Cancer Intergroup (GCIG) specific criteria\]; and
• •* Documented disease progression during or immediately after last therapy according to any of the aforementioned criteria.
• •7. Wash-out periods: at least three weeks since the last anticancer therapy, including radiation therapy (RT) in more than 35% of the bone marrow; at least three weeks since the last biological/investigational therapy \[excluding monoclonal antibodies (MAbs)\]; at least four weeks since the last MAb-containing therapy; and at least six weeks since nitrosoureas and mitomycin C (systemic). In the case of hormonesensitive breast cancer progressing while on hormone therapy, the latter must be either stopped up to one week before or continued without changes during the trial.
• •8. Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before inclusion in the study):
• •* Platelet count ≥ 100 x 109/l, hemoglobin ≥ 9.0 g/dl and ANC ≥ 1.0 x 109/l.
• •* AST and ALT ≤ 3.0 x ULN, independently of the presence of liver metastases.
• •* AP ≤ 2.5 x ULN (≤ 5 x ULN if disease-related).
• •* Total bilirubin ≤ 1.5 x ULN.
• •* International Normalized Ratio (INR) \< 1.5 (except if patient is on oral anticoagulation therapy).
• •* Calculated creatinine clearance (CrCl) ≥ 50 ml/minute (using Cockcroft and Gault's formula; see APPENDIX 2).
• •* Albumin ≥ 2.5 g/dl.
• •9. Recovery to grade ≤ 1 from any AE derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or asthenia).
• •10. Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiplegated acquisition (MUGA) within normal range (according to institutional standards).
• •11. Women of childbearing potential must have a negative serum or urine pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six weeks after discontinuation of treatment. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and/or double barrier.