Concurrent Once Daily Versus Twice Daily Radiotherapy for Limited Stage Small Cell Lung Cancer (CONVERT)

• ClinicalTrials.gov Identifier: NCT00433563
• Recruitment Status: Completed
• First Posted: February 12, 2007
• Last Update Posted: September 8, 2022
• Sponsor: The Christie NHS Foundation Trust
• Collaborators: 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
• Information provided by (Responsible Party): The Christie NHS Foundation Trust

Tracking Information

• First Submitted Date: February 8, 2007
• First Posted Date: February 12, 2007
• Last Update Posted Date: September 8, 2022
• Study Start Date: April 2008
• Actual Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 8, 2013): Overall survival [ Time Frame: August 2015 ]
• Original Primary Outcome Measures (submitted: February 8, 2007): Overall survival

Current Secondary Outcome Measures (submitted: September 5, 2022)

• Local progression-free survival [ Time Frame: August 2015 ]
• Metastasis-free survival [ Time Frame: August 2015 ]
• Toxicity of treatment [ Time Frame: August 2015 ]
• Cytotoxic dose intensity [ Time Frame: August 2015 ]
• Radiotherapy dose intensity [ Time Frame: August 2015 ]

Original Secondary Outcome Measures (submitted: February 8, 2007)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Concurrent Once Daily Versus Twice Daily Radiotherapy for Limited Stage Small Cell Lung Cancer
• Official Title: A 2-Arm Randomized Controlled Trial of Concurrent Chemo-Radiotherapy Comparing Twice-Daily and Once-Daily Radiotherapy Schedules in Patients With Limited Stage Small Cell Lung Cancer (SCLC) and Good Performance Status [CONVERT]

Brief Summary

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.

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lung Cancer

Intervention

• 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

Study Arms

• 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

Publications *

• Tay RY, Fernandez-Gutierrez F, Foy V, Burns K, Pierce J, Morris K, Priest L, Tugwood J, Ashcroft L, Lindsay CR, Faivre-Finn C, Dive C, Blackhall F. Prognostic value of circulating tumour cells in limited-stage small-cell lung cancer: analysis of the concurrent once-daily versus twice-daily radiotherapy (CONVERT) randomised controlled trial. Ann Oncol. 2019 Jul 1;30(7):1114-1120. doi: 10.1093/annonc/mdz122.
• Salem A, Mistry H, Hatton M, Locke I, Monnet I, Blackhall F, Faivre-Finn C. Association of Chemoradiotherapy With Outcomes Among Patients With Stage I to II vs Stage III Small Cell Lung Cancer: Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2019 Mar 1;5(3):e185335. doi: 10.1001/jamaoncol.2018.5335. Epub 2019 Mar 14.
• Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, Bezjak A, Cardenal F, Fournel P, Harden S, Le Pechoux C, McMenemin R, Mohammed N, O'Brien M, Pantarotto J, Surmont V, Van Meerbeeck JP, Woll PJ, Lorigan P, Blackhall F; CONVERT Study Team. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017 Aug;18(8):1116-1125. doi: 10.1016/S1470-2045(17)30318-2. Epub 2017 Jun 20.
• Groom N, Wilson E, Faivre-Finn C. Effect of accurate heart delineation on cardiac dose during the CONVERT trial. Br J Radiol. 2017 May;90(1073):20170036. doi: 10.1259/bjr.20170036. Epub 2017 Mar 31.
• Colaco R, Sheikh H, Lorigan P, Blackhall F, Hulse P, Califano R, Ashcroft L, Taylor P, Thatcher N, Faivre-Finn C. Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer--evidence from a phase II trial. Lung Cancer. 2012 Apr;76(1):72-7. doi: 10.1016/j.lungcan.2011.09.015. Epub 2011 Oct 19.
• Sheikh H, Colaco R, Lorigan P, Blackhall F, Califano R, Ashcroft L, Taylor P, Thatcher N, Faivre-Finn C. Use of G-CSF during concurrent chemotherapy and thoracic radiotherapy in patients with limited-stage small-cell lung cancer safety data from a phase II trial. Lung Cancer. 2011 Oct;74(1):75-9. doi: 10.1016/j.lungcan.2011.01.020. Epub 2011 Feb 26.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 19, 2014): 547
• Original Enrollment (submitted: February 8, 2007): 532
• Actual Study Completion Date: January 2019
• Actual Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion/exclusion criteria:

• Either sex, age ≥18 years
• Performance status ECOG grade 0-1. Patients with PS 2 whose general condition is explained by obstructive/bulky disease likely to improve after the first cycle of chemotherapy can be included at the discretion of the local investigator. Patients with PS 2 as a result of comorbid conditions will be excluded.
• Histologically or cytologically confirmed SCLC
• No patients with mixed small-cell and non-small-cell histologic features
• No history of previous malignancy in the last 5 years (except non melanomatous skin or in-situ cervix carcinoma). Patients with previous malignancies (except breast cancer) and in remission for at least 5 years can be included.
• Limited stage disease (Veterans Administration Lung Cancer Study Group) ie patients whose disease can be encompassed within a radical radiation portal.
• No pleural or pericardial effusions proven to be malignant
• RT target volume acceptable by the local radiotherapist

• Pulmonary function

  1. FEV1 >1 litre or 40% predicted value
  2. KCO (DLCO/VA) >40%predicted

• Maximum of one of the following adverse biochemical factors:

  1. Serum alkaline phosphatase more than >1.5 times the upper limit of normal (ULN)
  2. Serum sodium < Lower limit of Normal
  3. Serum LDH > ULN
• Normal serum creatinine and calculated creatinine clearance >50 ml/min. If calculated creatinine clearance is <50 ml/mn according to the Cockroft and Gault formula, an EDTA clearance should be performed

• Adequate haematological function

  1. Neutrophils >1.5 x 109/l
  2. Platelets >100 x 109/l
• Adequate liver function: ALT & AST <= 2.5 x ULN
• No other previous or concomitant illness or treatment which in the opinion of the clinician will interfere with the trial treatments or comparisons
• No prior surgical resection of the primary tumour, no prior radiotherapy for lung cancer
• Considered fit to receive any of the trial regimens
• Female patients must satisfy the investigator that they are not pregnant, or are not of child-bearing potential, or are using adequate contraception. Men must also use adequate contraception, as etoposide is clastogenic.
• Patients must not be breastfeeding
• Patient has read the patient information sheet and has signed the consent form.
• Patients available for follow-up

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom
• Removed Location Countries: Belgium, Canada, France, Spain

Administrative Information

• NCT Number: NCT00433563
• Other Study ID Numbers: CDR0000531709; CHNT-CONVERT ( Other Identifier: Christie Hospital NHS Foundation Trust ); CHNT-CTAAC-CONVERT-C17052/A815 ( Other Grant/Funding Number: Cancer Research UK )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: The Christie NHS Foundation Trust
• Original Responsible Party: Not Provided
• Current Study Sponsor: The Christie NHS Foundation Trust
• Original Study Sponsor: Same as current

Collaborators

• 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

Investigators

• Study Chair: Corinne Faivre-Finn, MD; The Christie NHS Foundation Trust

• PRS Account: The Christie NHS Foundation Trust
• Verification Date: September 2022