Phase I Study of Lurbinectedin (PM01183) in Combination With Paclitaxel, With or Without Bevacizumab, in Selected Advanced Solid Tumors

This study is currently recruiting participants.
Verified March 2014 by PharmaMar
Sponsor:
Information provided by (Responsible Party):
PharmaMar
ClinicalTrials.gov Identifier:
NCT01831089
First received: April 2, 2013
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

Clinical trial of PM01183 in combination with paclitaxel, with or without bevacizumab, in patients with solid tumors


Condition Intervention Phase
Breast Cancer
Ovarian Cancer
Gynecological Cancer
Head and Neck Carcinoma
Non-small Cell Lung Cancer
Small Cell Lung Cancer
Non-squamous Cell Lung Cancer
Drug: PM01183 + paclitaxel +/- bevacizumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination With Weekly Paclitaxel, With or Without Bevacizumab, in Patients With Selected Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by PharmaMar:

Primary Outcome Measures:
  • To determine the maximum tolerated dose (MTD) and the recommended dose (RD) [ Time Frame: Around 24 months from the begining of the study ] [ Designated as safety issue: Yes ]
    To determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with weekly paclitaxel, with or without bevacizumab, in patients with selected advanced solid tumors.


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: Around 24 monts after the begining of the study ] [ Designated as safety issue: No ]
    To characterize the pharmacokinetics (PK) and to detect major drug-drug PK interactions

  • Preliminary antitumor activity. [ Time Frame: Every nine weeks, up to around 24 months from the begining of the study ] [ Designated as safety issue: No ]
    Antitumor activity will be measured clinically and/or radiologically according to the RECIST (Response Evaluation Criteria in Solid Tumors)

  • Information on quality of life (QoL) [ Time Frame: baseline, 9, 18 and 24 weeks ] [ Designated as safety issue: No ]
    Changes in Quality of Life scores over time will be evaluated according to the European Organization for Research and Treatment of Cancer (EORTC) questionnaire EORTC-QLQ-C15-pal

  • Pharmacogenomic (PGx) [ Time Frame: Around 24 months from the begining of the study ] [ Designated as safety issue: No ]
    Identification and validation of putative molecular markers associated with the clinical outcome of treated patients


Estimated Enrollment: 60
Study Start Date: September 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatmen
PM01183 + paclitaxel +/- bevacizumab
Drug: PM01183 + paclitaxel +/- bevacizumab

PM01183: 1 mg and 4 mg vials. Powder for concentrate for solution for infusion

paclitaxel: 6 mg/ml concentrate for solution for infusion

bevacizumab: 25 mg/ml concentrate for solution for infusion

Once a recommended dose is defined for the PM01183 and weekly paclitaxel combination, the feasibility of adding bevacizumab to this combination will be explored in a prospectively selected cohort of patients


Detailed Description:

Clinical trial to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with weekly paclitaxel, with or without bevacizumab. Once a recommended dose is defined for the PM01183 and weekly paclitaxel combination, the feasibility of adding bevacizumab to this combination will be explored in a selected cohort of patients to characterize the safety profile and feasibility of this combination, to obtain preliminary information on antitumor activity, to obtain preliminary information on quality of life (QoL), to characterize the pharmacokinetics (PK) of this combination and to detect major drug-drug PK interactions and PK/PD (pharmacokinetic/pharmacodynamic) correlation and to conduct an exploratory pharmacogenomic(PGx) analysis in patients with selected advanced solid tumors.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Voluntarily signed and dated written informed consent
  • Age between 18 and 75 years old (both inclusive)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1
  • Life expectancy ≥ 3 months.
  • Patients with a histologically/cytologically confirmed diagnosis of advanced and/or unresectable disease of any of the following tumors:

    1. Breast cancer
    2. Epithelial ovarian cancer or gynecological cancer
    3. Head and neck squamous cell carcinoma
    4. Non-small cell lung cancer
    5. Small cell lung cancer
    6. Platinum-refractory germ-cell tumors.
    7. Adenocarcinoma or carcinoma of unknown primary site
  • Adequate bone marrow, renal, hepatic, and metabolic function
  • Recovery to grade ≤ 1 or to baseline from any AE derived from previous treatment (excluding alopecia of any grade).
  • Pre-menopausal women must have a negative pregnancy test before study entry and agree to use a medically acceptable method of contraception throughout the treatment period and for at least six weeks after treatment discontinuation

Exclusion Criteria:

  • Prior treatment with PM01183 or weekly paclitaxel or nanoalbumin-paclitaxel
  • Patients who have previously discontinued paclitaxel-based regimes due to drug related toxicity.
  • Known hypersensitivity to bevacizumab or any component of its formulation
  • Patients who have previously discontinued bevacizumab-containing regimes due to drug-related toxicity.
  • More than three prior lines of chemotherapy
  • Less than three months since last taxane-containing therapy.
  • Wash-out period:

    1. Less than three weeks since the last chemotherapy-containing regimen
    2. Less than three weeks since the last radiotherapy dose
    3. Less than four weeks since last monoclonal antibody-containing therapy
  • Concomitant diseases/conditions:

Unstable angina, myocardial infarction, valvular heart disease, encephalopathy, ischemic attacks, hemorrhagic or ischemic cerebrovascular accident (CVA) or ongoing pulmonary embolism within last year, arrhythmia, hepatopathy, uncontrolled infection, hemoptysis or oxygen requiring dyspnea, known HIV infection, bleeding risk, muscular problems, peripheral neuropathy, Symptomatic or progressive brain metastases or leptomeningeal disease.

  • Men or pre-menopausal women who are not using an effective method of contraception as previously described; actively breast feeding women.
  • Patients who have pelvic irradiation with doses ≥ 45 Grays (Gy).
  • History of previous bone marrow and/or stem cell transplantation.
  • Confirmed bone marrow involvement
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01831089

Contacts
Contact: Sergio Szyldergemajn, MD +34 91-846-6068 sszyldergemajn@pharmamar.com

Locations
United States, New York
Not yet recruiting
New York, New York, United States
Spain
Recruiting
Madrid, Spain
Switzerland
Recruiting
Bellinzona, Switzerland
Sponsors and Collaborators
PharmaMar
  More Information

No publications provided

Responsible Party: PharmaMar
ClinicalTrials.gov Identifier: NCT01831089     History of Changes
Other Study ID Numbers: PM1183-A-007-13
Study First Received: April 2, 2013
Last Updated: March 31, 2014
Health Authority: United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Ovarian Neoplasms
Small Cell Lung Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms, Squamous Cell
Paclitaxel

ClinicalTrials.gov processed this record on April 14, 2014