S0222: Tirapazamine Combined With Chemo and RT in Limited-Stage Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00066742
First received: August 6, 2003
Last updated: February 27, 2013
Last verified: February 2013
  Purpose

This phase II trial is studying how well giving tirapazamine together with cisplatin, etoposide, and radiation therapy works in treating patients with limited-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Tirapazamine may make the tumor cells more sensitive to chemotherapy and radiation therapy. Combining chemotherapy and radiation therapy with tirapazamine may kill more tumor cells.


Condition Intervention Phase
Lung Cancer
Drug: cisplatin
Drug: etoposide
Drug: tirapazamine
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Tirapazamine (NSC-130181)/Cisplatin/Etoposide And Concurrent Thoracic Radiotherapy For Limited Stage Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Weekly during protocol treatment, then every 3 months for first year, then every 6 months for up to 3 years after enrollment. ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from date of enrollment until the date of death due to any cause. Patients last known to be alive were censored at the date of last conatct. Patients were followed for a maximum of 3 years from the date of enrollment.


Secondary Outcome Measures:
  • Response Rate (Confirmed and Unconfirmed Complete and Partial Responses Per RECIST) in the Subset of Patients With Measurable Disease at Baseline. [ Time Frame: After completeion of concurrent chemotherapy+radiation (Week 8); then after completion of consolidation chemotherapy (Week15); once off treatment, every 3 months until disease progression for a maximum of 3 years after enrollment. ] [ Designated as safety issue: No ]
    A complete response (CR) was defined as a complete disappearance of all disease with no new lesions. A partial response (PR) was defined as at least a 30% decrease under baseline of the sum of longest diameters of all target measurable lesions with no unequivocal progression of non-measurable disease and no new lesions. Both CR and PR had to be confirmed by a second determination at least 4 weeks apart. All disease had to be assessed using same method as baseline. Only patients with measurable disease at baseline were included in this analysis.

  • Progression-Free Survival [ Time Frame: At end of concurrent chemoradiotherapy (Week 8), then at end of consolidation chemotherapy (Week 15). After off treatment, every 3 months for the first 2 years then every 6 months for up to 3 years after enrollment. ] [ Designated as safety issue: No ]
    Progression was defined as a >= 20% increase in the sum of longest diameters of measurable lesions over the smallest sum observed or unequivocal progression of non-measurable disease or the appearance of any new lesion/site. Symptomatic deterioration was defined as a global deterioration of health status requiring discontinuation of treatment. Progression-free survival was defined as the time from the date of enrollment until the date of progression, symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at last contact date.


Enrollment: 72
Study Start Date: September 2003
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tirapazamine/cisplatin/etoposide and RT
tirapazamine/cisplatin/etoposide and RT
Drug: cisplatin

During Induction: 50 mg/m2/day, IV on Days 1, 8, 29, 36. 1 hour infusion

During Consolidation: 60 mg/m2 IV Day 1 only at the beginning of each cycle. 1 hour infusion.

Other Name: platinol
Drug: etoposide

During Induction: 50 mg/m2/day IV on Days 1 - 5, 29 - 33. 1 hour infusion.

During Consolidation: 120 mg/m2 IV Days 1, 2 and 3 at the beginning of each cycle. 1 hour infusion.

Other Name: VP-16
Drug: tirapazamine

During Induction:

260 mg/m2/day IV on days 1 and 29. 1 hour infusion

160 mg/m2/day IV on Days 8, 10, 12, 36, 38, 40. 1 hour infusion

Radiation: radiation therapy

RT given to a total dose of 4500 cGy in 25 fractions. 180 cGy per day for 5 days a week for 5 weeks. Radiotherapy Boost: There will be no break (other than the weekend) between induction radiation and the boost radiation. RT will be continued for an additional 1,600 cGy with 200 cGy fractions, daily except weekends. Dose will be prescribed to the central axis at isocenter.

Patients achieving a complete response after consolidation chemotherapy will receive PCI. PCI is to be delivered at 200 cGy daily to a total dose of 3,000 cGy in 15 fractions over three weeks.

Other Name: RT

Detailed Description:

OBJECTIVES:

I. Determine the overall survival of patients with limited stage small cell lung cancer treated with tirapazamine, cisplatin, and etoposide with concurrent thoracic radiotherapy followed by consolidation cisplatin and etoposide.

II. Determine the time to treatment failure and response (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with this regimen.

III. Determine the toxicity of this regimen in these patients. IV. Correlate baseline PAI-1, VEGF, OPN, and NDRG1 plasma markers with response and survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Chemoradiotherapy: Patients receive tirapazamine IV over 1 hour on days 1, 8, 10, 12, 29, 36, 38, and 40; cisplatin IV over 1 hour on days 1, 8, 29, and 36; and etoposide IV over 1 hour on days 1-5 and 29-33. Beginning on day 1 of chemotherapy, patients undergo thoracic radiotherapy once daily 5 days a week for 7 weeks.

Consolidation chemotherapy: Within 28 days after completion of radiotherapy, patients with stable or responding disease receive cisplatin IV over 1 hour on days 1 and 22 and etoposide IV over 1 hour on days 1-3 and 22-24.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2-3 months for 2 years and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 30-85 patients will be accrued for this study within 17 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed limited stage small cell lung cancer (SCLC)

    • Diagnosis by sputum cytology is allowed provided there is pathologic confirmation of disease
    • No positron-emission tomography scans for tumor staging
  • Measurable or non-measurable disease by CT scan, MRI, or x-ray

    • Disease must be present outside the area of any prior surgical resection
  • No metastatic disease, including brain metastases
  • No malignant pericardial or pleural effusion*, defined as 1 of the following:

    • Cytologically positive effusion
    • Exudative effusion not attributable to other etiologies NOTE: *Patients with effusions too small to tap are eligible
  • Patients must be offered participation in SWOG-S9925

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • SGOT or SGPT no greater than 2 times ULN

Renal

  • Creatinine clearance at least 50 mL/min* NOTE: *If calculated creatinine clearance is used, creatinine must be < 1.5 mg/dL

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Patients with significant clinical hearing loss must be willing to accept the potential for worsening of symptoms
  • No grade 1 or greater symptomatic sensory neuropathy
  • No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior biologic therapy for SCLC
  • No concurrent filgrastim (G-CSF) during radiotherapy administration

Chemotherapy

  • No prior chemotherapy for SCLC

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior thoracic or neck radiotherapy
  • No concurrent intensity-modulated radiotherapy

Surgery

  • See Disease Characteristics
  • At least 2 weeks since prior thoracic or major surgery and recovered

Other

  • No concurrent amifostine
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00066742

  Show 134 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Quynh-Thu X. Le, MD Stanford University
Study Chair: Stephen K. Williamson, MD University of Kansas
Study Chair: Primo N. Lara, MD University of California, Davis
Study Chair: Zelanna Goldberg, MD University of California, Davis
  More Information

Additional Information:
Publications:
Le Q, Moon J, Redman M, et al.: SWOG 0222: A phase II study of tirapazamine (NSC-130181, TPZ)/cisplatin/etoposide (PE) and concurrent thoracic radiotherapy (TRT) for limited stage small-cell lung cancer (LSCLC). [Abstract] J Clin Oncol 26 (Suppl 15): A-7523, 2008.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00066742     History of Changes
Other Study ID Numbers: NCI-2012-03042, S0222, U10CA032102, CDR0000318805
Study First Received: August 6, 2003
Results First Received: June 14, 2012
Last Updated: February 27, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
limited stage small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide phosphate
Tirapazamine
Cisplatin
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 20, 2014