Overview

This trial is active, not recruiting.

Condition non small cell lung cancer
Treatments docetaxel, carboplatin, bortezomib
Phase phase 1/phase 2
Sponsor Milton S. Hershey Medical Center
Collaborator Sanofi
Start date August 2008
End date August 2016
Trial size 6 participants
Trial identifier NCT00714246, PSU 26983

Summary

This is a phase I/II study. The phase I portion of the study will determine the maximum tolerated dose of bortezomib when administered in combination with carboplatin & docetaxel and to determine the efficacy of the combination for patients with advanced NSCLC. Phase II will determine time to progression and overall survival and determine changes in serum proteomics patterns before & after combination therapy.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model factorial assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
docetaxel, carboplatin, bortezomib PS341
Patients will be enrolled to Phase 1 at the following dose levels: Level 1 - Carboplatin (day 1) 5 AUC mg/ml/min), Docetaxel (day 1) 60 mg/m2, Bortezomib (day 1,4,8,11) 0.7 mg/m2. Level 2A - Carboplatin (day 1) 6 AUC mg/ml/min), Docetaxel (day 1) 60 mg/m2, Bortezomib (day 1,4,8,11) 0.7 mg/m2. Level 2B - Carboplatin (day 1) 6 AUC mg/ml/min), Docetaxel (day 1) 60 mg/m2, Bortezomib (day 1,4,8,11) 1.0 mg/m2. Level 3 - Carboplatin (day 1) 6 AUC mg/ml/min), Docetaxel (day 1) 75 mg/m2, Bortezomib (day 1,4,8,11) 0.7 mg/m2. Level 4 - Carboplatin (day 1) 6 AUC mg/ml/min), Docetaxel (day 1) 75 mg/m2, Bortezomib (day 1,4,8,11) 1.0 mg/m2. Level 5 - Carboplatin (day 1) 6 AUC mg/ml/min), Docetaxel (day 1) 75 mg/m2, Bortezomib (day 1,4,8,11) 1.3 mg/m2
(Experimental)
docetaxel, carboplatin, bortezomib PS341
Phase II recommended dose is the highest dose level at which less than 2 patients (out of 6) experience dose limiting toxicity. A maximum of 4 cycles (1 cycle = 21 days) of chemotherapy will be administered to patients. Patients who demonstrate an ongoing response at the end of the 4th cycle of chemotherapy, may receive 2 more cycles of treatment.

Primary Outcomes

Measure
Determine maximum tolerated dose of bortezomib when administered in combination with carboplatin & docetaxel for treatment of patients with advanced NSCLC cancer. Determine the response rate of the combination for patients with advanced NSCLC.
time frame: Expected average of 2 years

Secondary Outcomes

Measure
Define dose-limiting toxicities of the combination of carboplatin, docetaxel & bortezomib for patients with advanced NSCLC. Determine the time to progression & overall survival, assess toxicities, determine changes in serum proteomics patterns
time frame: Expected average of 2 years

Eligibility Criteria

Male or female participants from 18 years up to 90 years old.

Inclusion Criteria: - Histologically/cytologically confirmed stage IIIB (pleural or pericardial effusion) or stage IV NSCLC - Age > 18 years - ECOG PS < 2 - No prior chemotherapy - Measurable disease - Signed informed consent - Adequate bone marrow function - Adequate renal function - Adequate hepatic function Exclusion Criteria: - Untreated clinically active brain metastasis - Radiotherapy within 2 weeks prior to initiation of protocol therapy - Treatment with any investigational therapy within 4 weeks prior to enrollment - History of any cancer other than NSCLC (except non-melanoma skin cancer or carcinoma on situ of the cervix) within the last 5 years - Patients in their reproductive age group should use an effective method of birth control. Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. Patients who are breast-feeding will be excluded from the study. Women of childbearing potential must have a negative pregnancy test. - Major surgery within 3 weeks prior to enrollment - Use of immunosuppressive agents including systemic corticosteroids within 4 weeks prior to enrollment (corticosteroids are permitted as physiological replacement therapy or as supportive care for nausea and emesis) - Known history of Human immunodeficiency virus infection - Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the investigator - Concurrent serious medical infection or illness, or psychiatric illness likely to interfere with participation in this clinical study. - History of known hypersensitivity to docetaxel or other drugs formulated with polysorbate 80, bortezomib, boron or mannitol - Patient has Grade 2 peripheral neuropathy within 14 days before enrollment. - Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.

Additional Information

Official title Phase I/II Study of Bortezomib (PS-341) in Combination With Carboplatin and Docetaxel for Patients With Advanced Non-Small Cell Lung Cancer
Principal investigator Chandra P. Belani, MD
Description A chemotherapy efficacy plateau' has been reached for the treatment of patients with advanced or metastatic non-small cell lung cancer. Platinum-based two-drug combination is considered the current standard of care for the treatment of advanced NSCLC. There is a need to develop novel regimens to improve the outcome for patients with advanced NSCLC. The combination of carboplatin and docetaxel is effective for therapy of advanced NSCLC. This combination results in improved survival and quality of life for patients with advanced NSCLC. Docetaxel exhibits preclinical synergy with bortezomib. Hence we plan to perform a phase I/II study to define the maximum tolerated dose of bortezomib that can be administered in combination with docetaxel and carboplatin and subsequently evaluate the efficacy of the regimen for patients with advanced NSCLC.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Milton S. Hershey Medical Center.