Escalating Doses of PM01183 in Combination With Gemcitabine in Patients With Specific Unresectable Solid Tumors

NCT ID: NCT01970553

Last Updated: 2015-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2013-10-31

Brief Summary

Phase I multicenter, open-label, clinical and pharmacokinetic study of PM01183 in combination with gemcitabine 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 gemcitabine, to characterize the safety profile and feasibility of this combination in patients with selected advanced solid tumors, to characterize the pharmacokinetics (PK), to obtain preliminary information on the clinical antitumor activity in non-heavily pretreated selected solid tumor patients and to evaluate the pharmacogenomics (PGx) in tumor samples of patients exposed, in order to assess potential markers of response and/or resistance.

Conditions

Specific Advanced Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

lurbinectedin (PM01183) / gemcitabine

Patients will consecutively receive the following on Days 1 and 8 q3wk (three weeks = one treatment cycle):

• Gemcitabine: intravenous infusion of 800 mg/m2/day over 30 minutes,

immediately followed by:

• PM01183: intravenous infusion over one hour at a starting dose of 2.5 mg/day, flat dose (FD), both on Days 1 and 8 every 3 weeks

Group Type: EXPERIMENTAL

lurbinectedin (PM01183)

Intervention Type: DRUG

lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials

Gemcitabine

Intervention Type: DRUG

1000 mg vial, powder for injectable solution

Interventions

lurbinectedin (PM01183)

lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials

Intervention Type: DRUG

Gemcitabine

1000 mg vial, powder for injectable solution

Intervention Type: DRUG

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
• Life expectancy ≥ 3 months
• Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors:

1. Breast cancer

2. Epithelial ovarian cancer (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas)

3. Stromal uterine sarcomas

4. Non-small cell lung cancer (NSCLC)

5. Platinum-refractory or relapsed germ cell tumors

6. Adenocarcinoma of the exocrine pancreas

7. Biliary tract adenocarcinoma

8. Adenocarcinoma or carcinoma of unknown primary site

9. Advanced or unresectable mesothelioma

• At least three weeks since the last anticancer therapy,including radiation therapy (RT)
• Adequate bone marrow, renal, hepatic, and metabolic function
• Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiple-gated acquisition (MUGA) 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
• History of previous bone marrow and/or stem cell transplantation
• Prior treatment with gemcitabine-containing therapy for advanced disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergio Szyldergemajn, MD

Role: STUDY_CHAIR

Pharma Mar

Locations

Hospital Universitario Madrid Sanchinarro

Madrid, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

University College of London Hospital

London, , United Kingdom

Countries

Spain; United Kingdom

Other Identifiers

PM1183-A-004-10

Identifier Type: -

Identifier Source: org_study_id