Study Escalating Doses of PM01183 in Combination With Fixed Doxorubicin in Patients With Specific Advanced Unresectable Solid Tumors

Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination With Doxorubicin in Non-heavily Pretreated Patients With Selected Advanced Solid Tumors

Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination with Fixed Doxorubicin in Non- Heavily Pretreated Patients with Selected Advanced Solid Tumors to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with doxorubicin, to characterize the safety profile and feasibility of this combination, to characterize the pharmacokinetics (PK) of this combination, to obtain preliminary information on the clinical antitumor activity,to explore the feasibility, safety and efficacy of a potential improvable dose of this combination in selected tumor types [i.e. small cell lung cancer (SCLC) and endometrial cáncer] and to evaluate the pharmacogenomics (PGx) in tumor samples of patients exposed to PM01183 and doxorubicin at the RD in order to assess potential markers of response and/or resistance.

The study has currently met its primary end point and is now recruiting patients to be treated at the RD expansion cohort of selected tumor types, specifically: endometrial adenocarcinomas, neuroendocrine tumors, and small-cell lung cancer (SCLC).

Inclusion Criteria:

• Voluntarily written informed consent

• Age: between 18 and 75 years (both inclusive).

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1. Cohort of patients with SCLC and endometrial cáncer ECOG PS ≤ 2.

• Life expectancy ≥ 3 months.

• Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors:

  1. Breast cancer
  2. Soft-tissue sarcoma
  3. Primary bone sarcomas.
  4. Gynecologic tumors (endometrial adenocarcinomas, epithelial ovarian cancer...)
  5. Hepatocellular carcinoma
  6. Gastroenteropancreatic neuroendocrine tumors
  7. Small cell lung cancer (SCLC)
  8. Gastric cancer
  9. Bladder cancer
  10. Adenocarcinoma of unknown primary site

• At least three weeks since the last anticancer therapy, including radiotherapy

• Adequate bone marrow, renal, hepatic, and metabolic function

• Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within normal range (according to institutional standards).

• Women of childbearing potential must have a negative serum 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

Exclusion Criteria:

• Concomitant diseases/conditions:

  • History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
  • Symptomatic or any uncontrolled arrhythmia
  • Ongoing chronic alcohol consumption, or cirrhosis
  • Active uncontrolled infection.
  • Known human immunodeficiency virus (HIV) infection.
  • Any other major illness that, in the Investigator's judgment

• Brain metastases or leptomeningeal disease involvement.

• Men or women of childbearing potential who are not using an effective method of contraception

• Patients who have had radiation therapy in more than 35% of the bone marrow. This criterion will not apply to cohort of patients with SCLC and endometrial cáncer.

• History of previous bone marrow and/or stem cell transplantation.