Clinical trial NCT00551733: Carboplatin With Either Paclitaxel Poliglumex or Paclitaxel in Treating Women With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
Official title: Paclitaxel Poliglumex (CT-2103)/Carboplatin vs Paclitaxel/Carboplatin for the Treatment of Chemotherapy-Naïve Advanced Non-Small Cell Lung Cancer (NSCLC) in Women With Estradiol >30 pg/mL
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
Lead sponsor: CTI BioPharma
Sponsor class: INDUSTRY
First posted: 2007-10-31
Enrollment: 450
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as carboplatin, paclitaxel, and paclitaxel poliglumex, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving carboplatin together with paclitaxel poliglumex is more effective than giving carboplatin together with paclitaxel in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying carboplatin and paclitaxel poliglumex to see how well they work compared with carboplatin and paclitaxel in treating women with stage III, stage IV, or recurrent non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the overall survival of patients with chemotherapy-naïve stage IIIB or IV or recurrent non-small cell lung cancer treated with paclitaxel poliglumex and carboplatin vs paclitaxel and carboplatin.

Secondary

* Compare the progression-free survival of women treated with these regimens.
* Compare the disease control in women treated with these regimens.
* Compare the clinical benefit in women treated with these regimens.
* Compare the response rate in women treated with these regimens.
* Compare the quality of life of women treated with these regimens.
* Compare the safety and tolerability in women treated with these regimens.

OUTLINE: This is a multicenter study.

Patients are stratified according to age (≥ 60 vs \< 60 years old), geographical location (United States of America, Canada, or Australia vs the rest of the world), extent of disease (independent of brain metastases, i.e., brain metastases are not considered in determining extent of disease) (intrathoracic disease only vs extrathoracic disease), and ECOG performance status (0 or 1 vs 2). Patients will be randomized to 1 of 2 treatment arms.

* Arm I: Patients receive paclitaxel poliglumex IV over 10 minutes followed by carboplatin IV over 30 minutes on day 1.
* Arm II: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1.

In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before each course, and at the completion of study treatment by the Pain Assessment Patient Questionnaire, the Pulmonary Symptom Index, and the Functional Assessment of Cancer Therapy- Lung Cancer Subscale (FACT-LCS) (only in countries in which a validated translation is currently available).

After completion of study therapy, patients are followed at least monthly.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)

  * Cytologic specimens obtained by brushings, washings, or needle aspiration of a defined lesion or from a pleural effusion are acceptable; sputum cytology alone is not acceptable for determining cell type
* Must meet one of the following criteria:

  * Recurrent disease following completion of radiation or surgery
  * Stage IIIB disease and not a candidate for combined modality therapy (primary radiation therapy or surgery)
  * Stage IV disease
* Patients may have either measurable or nonmeasurable disease according to RECIST criteria
* Baseline estradiol \> 30 pg/mL

  * Patients on hormone replacement therapy are eligible provided baseline estradiol \> 30 pg/mL
* Patients with known brain metastases must have received standard antitumor treatment (e.g. whole brain radiation, stereotactic radioablation, or surgery) for their CNS metastases as defined by the site's institutional standards

  * Neurologic function must have been stable for 2 weeks before randomization and patients must either be off steroid therapy for their brain metastases or on a tapering regimen
  * Patients must have recovered from therapy for their brain metastases with no evidence of significant unstable neurological symptoms within the 4 weeks before study randomization
* No evidence of small cell carcinoma, carcinoid, or mixed small cell/non-small cell histology

PATIENT CHARACTERISTICS:

* Female
* ECOG performance score 0-2
* Life expectancy ≥ 12 weeks
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 10 g/dL (may be achieved with transfusion)
* Creatinine ≤ 1.5 times upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 times ULN (CTC grade 1) (patients with Gilbert syndrome or other hereditary bilirubin defects may be included regardless of bilirubin levels)
* SGOT and SGPT ≤ 2.5 times ULN (CTC grade 0 or 1) (5 times ULN \[CTC grade 0 to 2\] if due to liver metastases)
* Alkaline phosphatase ≤ 2.5 times ULN except for elevated alkaline phosphatase with laboratory documentation that demonstrates bone origin
* No pregnant women or nursing mothers
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 6 months after study participation
* No known hypersensitivity to study drugs or excipients
* Meets all of the following criteria:

  * No weight loss \> 10% in previous 6 months
  * Lactate dehydrogenase (LDH) ≤ 600 IU/L (central laboratory) regardless of weight loss
  * LDH ≤ 400 IU/L (central laboratory) and no weight loss ≥ 5% in previous 6 months
  * BMI ≤ 35
* No concurrent primary malignancies except for carcinoma in situ or non-melanoma skin cancer
* No neuropathy grade 2 or greater
* No clinically significant active infection for which active therapy is underway
* No unstable medical conditions including unstable angina or myocardial infarction within the past 6 months

  * Patients with evidence of cardiac conduction abnormalities are eligible if their cardiac status is stable
* No circumstance that would preclude completion of the study or the required follow-up

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Recovered from major surgery
* At least 7 days since prior local palliative radiotherapy
* At least 30 days since prior radiation therapy with curative intent
* At least 4 weeks since prior investigational therapy, unless local requirements are more stringent
* No prior systemic chemotherapy for the treatment of lung cancer, including systemic radiosensitizers used to treat brain metastases or any biologic agents
* No concurrent non-protocol-specified systemic antitumor therapy
* No concurrent amifostine, investigational agents, other cytotoxic agents for this disease
* No concurrent radiotherapy (with the exception of radiotherapy for brain or bone metastases for palliative purposes or radiotherapy for a condition other than NSCLC that was ongoing at the time of randomization)

  * Patients receiving palliative radiotherapy (treatment for symptomatic metastatic disease) may be treated while on study

Primary outcomes:
measure: Overall survival
Secondary outcomes:
measure: Progression-free survival
measure: Disease control
measure: Clinical benefit as defined by use of opiates, growth factors, and transfusions,
measure: Response rate as assessed by complete response or partial response per RECIST criteria
measure: Quality of life as assessed by Fact-LCS Scores and Pulmonary Symptom Index (PSI) Scores and Pain Scores
measure: Safety as assessed by NCI CTCAE Version 3
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Medical Specialists
state: Arizona
city: Burbank
country: United States
facility: Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center
state: California
city: Escondido
country: United States
facility: Southwest Cancer Care - Escondido
state: California
city: Montebello
country: United States
facility: Clinical Trials and Research Associates, Incorporated
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Fort Lauderdale
country: United States
facility: Broward Oncology Associates
state: Florida
city: Hollywood
country: United States
facility: Horizon Institute for Clinical Research
state: Florida
city: Chicago
country: United States
facility: Rush Cancer Institute at Rush University Medical Center
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Naperville
country: United States
facility: Hematology Oncology Consultants - Naperville
state: Illinois
city: Olympia Fields
country: United States
facility: Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
state: Illinois
city: New Albany
country: United States
facility: Cancer Center of Indiana
state: Indiana
city: Terre Haute
country: United States
facility: Providence Medical Group
state: Indiana
city: Vincennes
country: United States
facility: Family Medicine of Vincennes Clinical Trial Center
state: Indiana
city: Free Soil
country: United States
facility: West Michigan Regional Cancer and Blood Center
state: Michigan
city: Southfield
country: United States
facility: Newland Medical Associates PC - Southfield
state: Michigan
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic, PA at Forrest General
state: Mississippi
city: Columbia
country: United States
facility: Columbia Comprehensive Cancer Care Clinic
state: Missouri
city: Kansas City
country: United States
facility: Kansas City Cancer Centers - South
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
state: Missouri
city: Las Vegas
country: United States
facility: Las Vegas Cancer Center
state: Nevada
city: Reno
country: United States
facility: Veterans Affairs Medical Center - Reno
state: Nevada
city: Bronx
country: United States
facility: Lincoln Medical and Mental Health Center
state: New York
city: Staten Island
country: United States
facility: Richmond University Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Bismarck
country: United States
facility: Mid Dakota Clinic, PC
state: North Dakota
city: Canfield
country: United States
facility: Blood and Cancer Center, Incorporated
state: Ohio
city: Canton
country: United States
facility: Aultman Cancer Center at Aultman Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Bethlehem
country: United States
facility: Vita Hematology Oncology at St. Luke's Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Eastside
state: South Carolina
city: Collierville
country: United States
facility: Family Cancer Center, PLLC - Collierville
state: Tennessee
city: Germantown
country: United States
facility: Mid-South Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Southwest Regional Cancer Center - Central
state: Texas
city: Austin
country: United States
facility: Lone Star Oncology - Austin
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center at Sammons Cancer Center
state: Texas
city: Ogden
country: United States
facility: Utah Hematology Oncology, PC
state: Utah
city: Abingdon
country: United States
facility: Cancer Outreach Associates - Abingdon
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Cell Therapeutics, Incorporated
state: Washington
Study officials:
affiliation: CTI BioPharma
name: Fred B. Oldham, MD
role: STUDY_CHAIR
References:
citation: Langer CJ, O'Byrne KJ, Socinski MA, Mikhailov SM, Lesniewski-Kmak K, Smakal M, Ciuleanu TE, Orlov SV, Dediu M, Heigener D, Eisenfeld AJ, Sandalic L, Oldham FB, Singer JW, Ross HJ. Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naive advanced non-small cell lung cancer. J Thorac Oncol. 2008 Jun;3(6):623-30. doi: 10.1097/JTO.0b013e3181753b4b.