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

NCT01970553 | Completed Phase 1

• 1 other identifier: PM1183-A-004-10
• Study Type: interventional
• Target: 47
• Locations: 2 countries
• Sites: 3

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

Keywords

lurbinectedin; PM01183; tumors; cancer; Pharma Mar

Outcome Measures

Primary Outcomes (1)

• Recommended Dose (RD)

  The RD will be the highest dose level explored at which less than one third of evaluable patients experience a DLT during Cycle 1.

  19 months

Secondary Outcomes (3)

• Pharmacokinetics (PK) characterisation

  19 months

• Preliminary antitumor efficacy

  29 months

• Pharmacogenomics (PGx)

  29 months

Study Arms (1)

lurbinectedin (PM01183) / gemcitabine

EXPERIMENTAL

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

Drug: lurbinectedin (PM01183); Drug: Gemcitabine

Interventions

lurbinectedin (PM01183) DRUG

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

lurbinectedin (PM01183) / gemcitabine

Gemcitabine DRUG

1000 mg vial, powder for injectable solution

lurbinectedin (PM01183) / gemcitabine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Breast cancer
• Epithelial ovarian cancer (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas)
• Stromal uterine sarcomas
• Non-small cell lung cancer (NSCLC)
• Platinum-refractory or relapsed germ cell tumors
• Adenocarcinoma of the exocrine pancreas
• Biliary tract adenocarcinoma
• Adenocarcinoma or carcinoma of unknown primary site
• Advanced or unresectable mesothelioma
• At least three weeks since the last anticancer therapy,including radiation therapy (RT)

You may not qualify if:

• 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

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (3)

Hospital Universitario Madrid Sanchinarro

Madrid, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

University College of London Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

PM 01183; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Sergio Szyldergemajn, MD

  Pharma Mar

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2013
• First Posted: October 28, 2013
• Study Start: May 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: April 1, 2015

Record last verified: 2013-10

Locations

ES (2); GB (1)