Cisplatin, Etoposide, and Two Different Schedules of Radiation Therapy in Treating Patients With Limited Stage Small Cell Lung Cancer (CONVERT)

• Local progression-free survival [ Time Frame: August 2015 ] [ Designated as safety issue: No ]
• Metastasis-free survival [ Time Frame: August 2015 ] [ Designated as safety issue: No ]
• Toxicity [ Time Frame: August 2015 ] [ Designated as safety issue: Yes ]
• Cytotoxic dose intensity [ Time Frame: August 2015 ] [ Designated as safety issue: Yes ]
• Radiotherapy dose intensity [ Time Frame: August 2015 ] [ Designated as safety issue: No ]

• Local progression-free survival
• Metastasis-free survival
• Toxicity
• Response rate
• Cytotoxic dose intensity
• Radiotherapy dose intensity

RATIONALE: Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known which schedule of radiation therapy is more effective when given together with chemotherapy in treating small cell lung cancer.

PURPOSE: This randomized phase III trial is studying two different schedules of radiation therapy to compare how well they work when given together with cisplatin and etoposide in treating patients with limited stage small cell lung cancer.

OBJECTIVES:

Primary

• Compare overall survival of patients with limited stage small cell lung cancer treated with chemoradiotherapy comprising cisplatin, etoposide, and once vs twice daily radiotherapy.

Secondary

• Compare local progression-free survival of patients treated with these regimens.
• Compare metastasis-free survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare response rates in patients treated with these regimens.
• Compare the cytotoxic dose intensity of these regimens in these patients.
• Compare the dose intensity of two different schedules of radiotherapy in these patients.

OUTLINE: This is a multicenter, randomized, controlled study. Patients are stratified according to participating center, ECOG performance status (0-1 vs 2), and lactic dehydrogenase, sodium, and alkaline phosphatase levels. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cisplatin IV over 2 hours on days 1-3 OR on day 1 only and etoposide IV over 45-90 minutes on days 1-3. Treatment repeats every 21 days for up to 6 courses. During course 2, patients undergo concurrent radiotherapy once daily 5 days a week for 6½ weeks (total of 33 fractions).
• Arm II: Patients receive cisplatin and etoposide as in arm I. During courses 2 and 3, patients undergo concurrent radiotherapy twice daily 5 days a week for 3 weeks (total of 30 fractions).

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Beginning 3-4 weeks after completion of chemoradiotherapy, patients in both arms achieving a complete or partial response with no evidence of brain metastasis undergo prophylactic cranial irradiation once daily 5 days a week for 2 weeks (total of 10 fractions).

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 532 patients will be accrued for this study.

• Radiation: Once daily radiotherapy
  Standard of care chemotherapy (cisplatin/etoposide) + once daily radiotherapy
• Radiation: Twice daily radiotherapy
  Standard of care chemotherapy (cisplatin/etoposide) + twice daily radiotherapy

• Experimental: Once daily radiotherapy
  Once daily radiotherapy
  Interventions:

  • Radiation: Once daily radiotherapy
  • Radiation: Twice daily radiotherapy
• Active Comparator: Twice daily radiotherapy
  Twice daily radiotherapy
  Interventions:

  • Radiation: Once daily radiotherapy
  • Radiation: Twice daily radiotherapy

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer

  • Limited stage disease that can be encompassed within a radical radiation portal
  • No mixed small cell or non-small cell histologic features

• No more than 1 of the following adverse factors:

  • Alkaline phosphatase > 1.5 times upper limit of normal
  • Sodium < lower limit of normal
• No malignant pleural or pericardial effusions

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Absolute neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³
• Creatinine normal
• Creatinine clearance ≥ 50 mL/min
• FEV_1 > 1 L OR > 40% of predicted
• DLCO > 40% of predicted
• No other medical condition that would preclude study treatment
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior surgical resection of the primary tumor
• No prior radiotherapy for lung cancer
• No other prior or concurrent therapy that would preclude study treatment
• No concurrent epoetin alfa for anemia
• No concurrent sargramostim (GM-CSF)

• Cancer Research UK
• NCIC Clinical Trials Group
• European Organisation for Research and Treatment of Cancer - EORTC
• Spanish Lung Cancer Group
• Groupe Francais De Pneumo-Cancerologie
• Intergroupe Francophone de Cancerologie Thoracique