3-AP and Gemcitabine as Second-Line Therapy in Treating Patients With Stage III or Stage IV Recurrent Non-Small Cell Lung Cancer

Cancer Therapeutics Research Group

Status and phase

Completed

Phase 2

Conditions

Lung Cancer

Treatments

Drug: gemcitabine hydrochloride

Drug: triapine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00077415

NCI-6256

CTRG-LUN012

CDR0000350313 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

31 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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