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

NCT ID: NCT01831089

Last Updated: 2020-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2016-07-31

Brief Summary

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

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(pharmacokinetic)/PD(pharmacodynamic) correlation and to conduct an exploratory pharmacogenomic(PGx) analysis in patients with selected advanced solid tumors.

Conditions

Breast Cancer; Ovarian Cancer; Gynecological Cancer; Head and Neck Carcinoma; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Non-squamous Cell Lung Cancer

Study Design

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

Study Groups

Treatment

PM01183 + paclitaxel +/- bevacizumab

Group Type: EXPERIMENTAL

PM01183 + paclitaxel +/- bevacizumab

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Eligibility 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 Adverse Event (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

• 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

Locations

New York, New York, United States

Madrid, , Spain

Bellinzona, , Switzerland

Countries

United States; Spain; Switzerland

Other Identifiers

PM1183-A-007-13

Identifier Type: -

Identifier Source: org_study_id