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

NCT01831089 | Completed Phase 1 Results

• 1 other identifier: PM1183-A-007-13
• Study Type: interventional
• Target: 69
• Locations: 3 countries
• Sites: 3

Brief Summary

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

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD)

  The MTD will be the lowest level at which one third or more evaluable patients experience a DLT in Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.

  The MTD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)

• Recommended Dose (RD)

  The RD will be the highest DL explored with less than one third of the patients experiencing a DLT during Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.

  The RD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)

• Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

  DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.

  DLT was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)

Secondary Outcomes (4)

• Best Tumor Response

  Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)

• Progression-free Survival

  Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)

• Duration of Response (DR)

  Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)

• Quality of Life (QoL)

  Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks)

Study Arms (1)

Treatment

EXPERIMENTAL

PM01183 + paclitaxel +/- bevacizumab

Drug: PM01183 + paclitaxel +/- bevacizumab

Interventions

PM01183 + paclitaxel +/- bevacizumab 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

Treatment

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 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:
• Breast cancer
• Epithelial ovarian cancer or gynecological cancer
• Head and neck squamous cell carcinoma
• Non-small cell lung cancer
• Small cell lung cancer
• Platinum-refractory germ-cell tumors.
• 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

You may not qualify if:

• 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:
• Less than three weeks since the last chemotherapy-containing regimen
• Less than three weeks since the last radiotherapy dose
• 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.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (3)

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Bellinzona, Switzerland

Location

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Interventions

PM 01183

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Clinical Development Department of PharmaMar´s Oncology Business Unit.
• Organization: Pharma Mar, S.A.

clinicaltrials@pharmamar.com

+34 91 846 60 00

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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: April 2, 2013
• First Posted: April 15, 2013
• Study Start: September 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: April 10, 2020
• Results First Posted: March 20, 2020

Record last verified: 2020-03

Locations

US (1); ES (1); CH (1)