Clinical trial NCT00723957: A Randomized Phase 2 Study of Ixabepilone Plus Carboplatin and Paclitaxel Plus Carboplatin in Advanced Nonsmall-Cell Lung Cancer
Official title: A Randomized Phase 2 Study of Ixabepilone Plus Carboplatin and Paclitaxel Plus Carboplatin in Patients With Advanced Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced/Metastatic Non-Small Cell Lung Cancer
Lead sponsor: R-Pharm
Sponsor class: INDUSTRY
First posted: 2008-07-29
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether progression-free survival with ixabepilone is superior to that achieved with paclitaxel plus carboplatin in participants with advanced nonsmall-cell lung cancer and beta III (βIII)-tubulin-positive tumors.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed non-small cell lung cancer (NSCLC)(squamous cell, adenocarcinoma, large cell, or bronchoalveolar carcinoma)
* Stage IIIB NSCLC with pleural effusion, Stage IV NSCLC, or recurrent disease following surgery with or without radiation therapy
* Available paraffin-embedded tissue to measure the expression levels of βIII tubulin
* Disease measurable by Response Evaluation Criteria in Solid Tumors, with at least 1 target lesion situated outside any previous radiotherapy field
* Karnofsky performance status of 70-100
* Life expectancy of at least 3 months
* Men and women, ages 18 years and older

Exclusion Criteria:

* Uncontrolled brain metastases
* Peripheral neuropathy greater than Grade 1
* Fewer than 4 weeks from prior radiation therapy or locoregional surgeries to randomization date (less than 1 week from focal/palliative radiotherapy or minor surgery)
* Any concurrent malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix
* Known HIV-positive status
* Absolute neutrophil count lower than 1500 cells mm\^3
* Total bilirubin level higher than upper limit of normal (ULN) as defined by the institution (with the exception of elevation due to Gilbert's syndrome)
* Aspartate transaminase or alanine transaminase level higher than 2.5\*ULN
* Serum creatine level of 1.5 mg/dL or higher
* Renal function with a creatinine clearance of less than 50 mL/min (as calculated with the Cockcroft and Gault equation)
* Any prior antineoplastic systemic regimens.

Primary outcomes:
measure: Progression-free Survival in the Subgroup of Participants With βIII-tubulin Positive Tumors
timeFrame: Randomization to disease progression or death (maximum reached: 14.39 months )
Secondary outcomes:
measure: Progression-free Survival in the Subgroup of Participants With βIII-tubulin Negative Tumors
timeFrame: Randomization to disease progression or death (maximum reached: 12.29 months)
measure: Progression-free Survival in the Overall Population
timeFrame: Randomization to disease progression or death, assessed to 12.29 months
measure: Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR)
timeFrame: At randomization and then every 6 weeks to date of CR, PR, or progression for 6 21-day cycles
measure: Time to Response
timeFrame: Randomization to date of first response (PR or CR)
measure: Number of Participants With Death as Outcome, Drug-related Adverse Events (AEs), Serious AEs (SAEs), Drug-related SAEs, AEs Leading to Discontinuation, and Drug-related Peripheral Neuropathy
timeFrame: Days 1 through 21, continuously
measure: Number of Participants With Hematology Laboratory Results of Grade 3 or 4
timeFrame: At screening and weekly during 21-day cycle
measure: Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results
timeFrame: At screening and within 72 hours of start of 21-day cycle (Cycle 2 and beyond)
measure: Median Length of Survival in the Overall Population and in the Subgroups of Patients With βIII-tubulin Positive (β3T+) and βIII-tubulin Negative (β3T-)Tumors
timeFrame: Randomization to death or last known alive date, up to 31.34 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Cancer Center
state: California
city: Baltimore
country: United States
facility: Uof Md,Greenebaum Cancer Ctr.
state: Maryland
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Bankstown
country: Australia
facility: Local Institution
state: New South Wales
city: Frankston
country: Australia
facility: Local Institution
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution
state: Western Australia
city: Poitiers
country: France
facility: Local Institution
city: Strasbourg
country: France
facility: Local Institution
city: Strasbourg
country: France
facility: Local Institution
city: Bad Berka
country: Germany
facility: Local Institution
city: Grosshansdorf
country: Germany
facility: Local Institution
city: Ulm
country: Germany
facility: Local Institution
city: Genova
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Sondrio
country: Italy
facility: Local Institution
city: Terni
country: Italy
facility: Local Institution
city: Goyang-Si
country: Korea, Republic of
facility: Local Institution
state: Gyeonggi-Do
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Chelyabinsk
country: Russian Federation
facility: Local Institution
city: Kazan
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Ryazan
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Baracaldo (Vizcaya)
country: Spain
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taoyuan Hsien
country: Taiwan
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Edelman MJ, Schneider CP, Tsai CM, Kim HT, Quoix E, Luft AV, Kaleta R, Mukhopadhyay P, Trifan OC, Whitaker L, Reck M. Randomized phase II study of ixabepilone or paclitaxel plus carboplatin in patients with non-small-cell lung cancer prospectively stratified by beta-3 tubulin status. J Clin Oncol. 2013 Jun 1;31(16):1990-6. doi: 10.1200/JCO.2012.45.3282. Epub 2013 Apr 15.