Bortezomib (PS-341) in Combination With Carboplatin and Docetaxel for Patients With Advanced Non-Small Cell Lung Cancer

NCT00714246 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PSU 26983
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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 utilize the dosage determined in the Phase I and implement regimen to determine time to progression, overall survival, and changes in serum proteomics patterns before \& after combination therapy.

Conditions

Non Small Cell Lung Cancer

Keywords

advanced non small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Expected average of 2 years

Secondary Outcomes (1)

• 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

  Expected average of 2 years

Study Arms (7)

Phase I - Dose Level 1

EXPERIMENTAL

Carboplatin AUC 5 mg/ml/min (Day 1) Docetaxel 60 mg/m2 (Day 1) Bortezomib 0.7 mg/m2 (Day 1,4,8,11)

Drug: Bortezomib; Drug: Carboplatin; Drug: Docetaxel

Phase I - Dose Level 2A

EXPERIMENTAL

Carboplatin AUC 6 mg/ml/min (Day 1) Docetaxel 60 mg/m2 (Day 1) Bortezomib 0.7 mg/m2 (Day 1,4,8,11)

Drug: Bortezomib; Drug: Carboplatin; Drug: Docetaxel

Phase I - Dose Level 2B

EXPERIMENTAL

Carboplatin AUC 6 mg/ml/min (Day 1) Docetaxel 60 mg/m2 (Day 1) Bortezomib 1.0 mg/m2 (Day 1,4,8,11)

Drug: Bortezomib; Drug: Carboplatin; Drug: Docetaxel

Phase I - Dose Level 3

EXPERIMENTAL

Carboplatin AUC 6 mg/ml/min (Day 1) Docetaxel 60 mg/m2 (Day 1) Bortezomib 1.0 mg/m2 (Day 1,4,8,11)

Drug: Bortezomib; Drug: Carboplatin; Drug: Docetaxel

Phase I - Dose Level 4

EXPERIMENTAL

Carboplatin AUC 6 mg/ml/min (Day 1) Docetaxel 75 mg/m2 (Day 1) Bortezomib 1.0 mg/m2 (Day 1,4,8,11)

Drug: Bortezomib; Drug: Carboplatin; Drug: Docetaxel

Phase I - Dose Level 5

EXPERIMENTAL

Carboplatin AUC 6 mg/ml/min (Day 1) Docetaxel 75 mg/m2 (Day 1) Bortezomib 1.3 mg/m2 (Day 1,4,8,11)

Drug: Bortezomib; Drug: Carboplatin; Drug: Docetaxel

Phase II

EXPERIMENTAL

Carboplatin AUC 5 mg/ml/min (Day 1) Docetaxel 60 mg/m2 (Day 1) Bortezomib 0.7 mg/m2 (Day 1,4,8,11)

Drug: Bortezomib; Drug: Carboplatin; Drug: Docetaxel

Interventions

Bortezomib DRUG

Dose escalation using traditional Phase I - 3 x 3 design to establish MTD of bortezomib when administered in combination with carboplatin and docetaxel

Also known as: VELCADE, PS-341

Phase I - Dose Level 1; Phase I - Dose Level 2A; Phase I - Dose Level 2B; Phase I - Dose Level 3; Phase I - Dose Level 4; Phase I - Dose Level 5; Phase II

Carboplatin DRUG

Establish MTD of bortezomib when administered in combination with carboplatin and docetaxel

Also known as: Paraplatin

Phase I - Dose Level 1; Phase I - Dose Level 2A; Phase I - Dose Level 2B; Phase I - Dose Level 3; Phase I - Dose Level 4; Phase I - Dose Level 5; Phase II

Docetaxel DRUG

Establish MTD of bortezomib when administered in combination with carboplatin and docetaxel

Also known as: Taxotere

Phase I - Dose Level 1; Phase I - Dose Level 2A; Phase I - Dose Level 2B; Phase I - Dose Level 3; Phase I - Dose Level 4; Phase I - Dose Level 5; Phase II

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• Sanofi: collaborator

Study Sites (1)

Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Bortezomib; Carboplatin; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Chandra P. Belani, MD

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 7, 2008
• First Posted: July 14, 2008
• Study Start: October 1, 2008
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 24, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)