Clinical trial NCT00052338: Bortezomib Plus Gemcitabine and Carboplatin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer
Official title: A Phase I Study Of PS-341 In Combination With Gemcitabine And Carbloplatin In Selected Stage IIIB Or IV Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Pleural Effusion
Recurrent Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug and bortezomib may kill more tumor cells

Detailed description: PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of combining bortezomib with gemcitabine and carboplatin in patients with advanced or recurrent non-small cell lung cancer.

II. Determine the maximum tolerated dose of bortezomib administered in combination with gemcitabine and carboplatin in these patients.

III. Correlate results from laboratory studies on patient tissue and serum specimens with potential predictors of response in patients treated with this regimen.

IV. Determine, preliminarily, the response of patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of bortezomib.

Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 15-30 minutes on day 1, followed 1 hour later by bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with a clinical or radiographic response may continue receiving bortezomib beyond 6 courses.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 10 additional patients with chemotherapy-naive disease receive treatment as above with the MTD of bortezomib.

Patients are followed for survival.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed non-small cell lung cancer

  * Selected stage IIIB (malignant pleural effusion) or stage IV disease
  * Recurrent disease after first-line therapy allowed
* Patients who received prior platinum-based chemotherapy must have no disease progression during or within 3 months after completion of therapy

  * Patients who are enrolled at the maximum tolerated dose must have chemotherapy-naïve disease
* Evaluable disease
* Asymptomatic brain metastases allowed if treated with surgical resection or radiotherapy, neurologically stable, and off steroids for at least 4 weeks
* Performance status - Karnofsky 60-100%
* More than 3 months
* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Bilirubin no greater than 1.5 mg/dL
* AST no greater than 2.5 times upper limit of normal
* Creatinine normal
* Creatinine clearance at least 50 mL/min
* No symptomatic congestive heart failure
* No unstable angina pectoris
* No cardiac arrhythmia
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No peripheral neuropathy grade 2 or greater
* No prior allergic reactions to compounds of similar chemical or biological composition to bortezomib or other agents used in this study
* No concurrent ongoing or active infection
* No other concurrent uncontrolled illness
* No psychiatric illness or social situation that would preclude study compliance
* No concurrent routine filgrastim (G-CSF)
* See Disease Characteristics
* No more than 1 prior chemotherapy regimen
* At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
* No prior gemcitabine
* See Disease Characteristics
* See Disease Characteristics
* At least 4 weeks since prior radiotherapy and recovered
* See Disease Characteristics
* More than 30 days since prior investigational drugs
* No prior bortezomib
* No concurrent anticonvulsant therapy
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No other concurrent investigational or commercial agents or therapies with intent to treat malignancy

Primary outcomes:
measure: Toxicities at each dose level, graded using the CTC version 2.0
timeFrame: 18 weeks
Secondary outcomes:
measure: Response rate, assessed by standard RECIST criteria
timeFrame: Up to 2 years
measure: Survival
timeFrame: From registration to time of death due to any cause, assessed up to 2 years
measure: Time to failure
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Angela Davies
role: PRINCIPAL_INVESTIGATOR
References: