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

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: triapine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • Sydney Cancer Centre at Royal Prince Alfred Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital - Perth
• Hong Kong
  • Shatin, New Territories, Hong Kong
    • Prince of Wales Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Yonsei Cancer Center at Yonsei University Medical Center
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre - Singapore
  • Singapore, Singapore, 308433
    • Johns Hopkins Singapore International Medical Centre
  • Singapore, Singapore, 119074
    • Cancer Institute at National University Hospital
  • Singapore, Singapore, 119260
    • National University of Singapore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Objective tumor response as assessed by RECIST criteria

Secondary Outcome Measures

Outcome Measure
Overall survival
Pharmacokinetics
Median time to progression
Toxicity as assessed by NCI CTCAE v3.0
Duration of overall response

Collaborators and Investigators

• Sponsor: Cancer Therapeutics Research Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Brigette Ma, MD, Prince of Wales Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (ACTUAL): January 1, 2008
• Study Completion (ACTUAL): February 1, 2008

Study Registration Dates

• First Submitted: February 10, 2004
• First Submitted That Met QC Criteria: February 11, 2004
• First Posted (ESTIMATE): February 12, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): May 15, 2013
• Last Update Submitted That Met QC Criteria: May 14, 2013
• Last Verified: August 1, 2006

More Information

Terms related to this study

• 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; squamous cell lung cancer; large cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: CTRG-LUN012; CDR0000350313 (REGISTRY: PDQ (Physician Data Query)); NCI-6256