Clinical trial NCT00077415: 3-AP and Gemcitabine as Second-Line Therapy in Treating Patients With Stage III or Stage IV Recurrent Non-Small Cell Lung Cancer
Official title: A Randomized Phase II Study Of Triapine® Alone Versus Triapine and Gemcitabine As Second-Line Treatment Of Advanced Non-Small-Cell-Lung Cancer In Patients Who Had Prior Gemcitabine With Evaluation Of The Effect Of Triapine® On Gemcitabine Pharmacokinetics and Cellular Uptake In Peripheral Mononuclear Cells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
adenocarcinoma of the lung
bronchoalveolar cell lung cancer
large cell lung cancer
squamous cell lung cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-02-12
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as 3-AP and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving 3-AP together with gemcitabine as second-line therapy works in treating patients with recurrent stage III or stage IV non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the objective response rate in patients with stage III or IV recurrent non-small cell lung cancer treated with 3-AP (Triapine®) and gemcitabine as second-line therapy.

Secondary

* Determine the response duration, median time to progression, and overall survival of patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.
* Determine the effect of 3-AP (Triapine®) on gemcitabine pharmacokinetics and cellular uptake into peripheral mononuclear cells in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to participating center.

Patients receive 3-AP (Triapine®) IV over 4 hours and gemcitabine IV over 30 minutes on days 1, 8, and 15\*. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

NOTE: \*For course 1 only, gemcitabine is administered alone on day 1 and in combination with 3-AP (Triapine®) on days 8 and 15.

Patients are followed every 3 months for up to 2 years.

PROJECTED ACCRUAL: A total of 15-31 patients will be accrued for this study within 7.5-21 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

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

  * Stage III or IV disease
  * One of the following cellular types:

    * Adenocarcinoma
    * Non-diffuse bronchoalveolar cell carcinoma
    * Large cell carcinoma
    * Squamous cell carcinoma NOTE: \*A repeat biopsy of any accessible tumor site is required if \> 5 years have elapsed since the initial diagnosis
* Progressive disease after 1 prior gemcitabine-containing chemotherapy regimen for stage III or IV NSCLC and must have achieved, at least once, a partial response, complete response, or stable disease during therapy

  * Not a primary non-responder and experienced only progressive disease during gemcitabine-containing chemotherapy
* Measurable disease

  * At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
* No known brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2 OR
* Karnofsky 60-100%

Life expectancy

* Not specified

Hematopoietic

* WBC ≥ 3,000/mm\^3
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* No glucose-6-phosphate dehydrogenase (G6PD) deficiency

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)

Renal

* Creatinine ≤ 1.5 times ULN OR
* Creatinine clearance ≥ 50 mL/min

Cardiovascular

* No prior uncontrolled cardiac disease
* No myocardial infarction within the past 12 months
* No symptomatic congestive heart failure
* No coronary artery disease
* No cardiac arrhythmia

Pulmonary

* No uncontrolled symptomatic pulmonary disease
* No pulmonary disease that requires oxygen therapy

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other malignancy within the past 5 years except completely treated carcinoma in situ of the cervix or nonmelanoma skin cancer
* No prior allergic reaction attributed to compounds of similar chemical or biological composition to study agents
* No other concurrent uncontrolled illness
* No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* See Disease Characteristics
* More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

* Not specified

Radiotherapy

* More than 4 weeks since prior radiotherapy and recovered

Surgery

* Not specified

Other

* No concurrent combination antiretroviral therapy for HIV-positive patients
* No other concurrent investigational agents
* No other concurrent anticancer agents or therapies

Primary outcomes:
measure: Objective tumor response as assessed by RECIST criteria
Secondary outcomes:
measure: Toxicity as assessed by NCI CTCAE v3.0
measure: Overall survival
measure: Median time to progression
measure: Duration of overall response
measure: Pharmacokinetics
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Sydney Cancer Centre at Royal Prince Alfred Hospital
state: New South Wales
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital - Perth
state: Western Australia
city: Shatin, New Territories
country: Hong Kong
facility: Prince of Wales Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei Cancer Center at Yonsei University Medical Center
city: Singapore
country: Singapore
facility: Cancer Institute at National University Hospital
city: Singapore
country: Singapore
facility: National University of Singapore
city: Singapore
country: Singapore
facility: National Cancer Centre - Singapore
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Centre
Study officials:
affiliation: Prince of Wales Hospital
name: Brigette Ma, MD
role: STUDY_CHAIR
References: