Study Escalating Doses of PM01183 in Combination With Fixed Doxorubicin in Patients With Specific Advanced Unresectable Solid Tumors
Condition: Endometrial Adenocarcinomas; Neuroendocrine Tumors; Small-cell Lung Cancer With Less Than 2 Prior Cytotoxic-containing Lines of Therapy
MeSH terms: Small Cell Lung Carcinoma; Neuroendocrine Tumors
Intervention: lurbinectedin (PM01183); Doxorubicin
Intervention description: lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials.; Commercially available presentations of vials containing doxorubicin will be provided as appropriate.
Intervention MeSH terms: Doxorubicin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 122.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: lurbinectedin; PM01183; tumors; cancer; Pharma Mar

Summary:

      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.
    

Eligibility criteria:

        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.