PET Scan in Planning Treatment in Patients Undergoing Combination Chemotherapy For Stage IA or Stage IIA Hodgkin Lymphoma (RAPID)

• ClinicalTrials.gov Identifier: NCT00943423
• Recruitment Status: Active, not recruiting
• First Posted: July 22, 2009
• Last Update Posted: November 30, 2023
• Sponsor: University College, London
• Collaborator: The Christie NHS Foundation Trust
• Information provided by (Responsible Party): University College, London

Tracking Information

• First Submitted Date: July 20, 2009
• First Posted Date: July 22, 2009
• Last Update Posted Date: November 30, 2023
• Study Start Date: July 2003
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 9, 2013): Progression-free survival [ Time Frame: up to 5 years after randomisation ]
• Original Primary Outcome Measures (submitted: July 21, 2009): Progression-free survival

Current Secondary Outcome Measures (submitted: May 9, 2013)

• Incidence of FDG-PET scan positivity/negativity after 3 courses of chemotherapy [ Time Frame: 3 months after treatment start ]
• Survival and cause of death [ Time Frame: up to 5 years after randomisation ]
• Incidence and type of second cancers [ Time Frame: up to 5 years after randomisation ]

Original Secondary Outcome Measures (submitted: July 21, 2009)

• Incidence of FDG-PET scan positivity/negativity after 3 courses of chemotherapy
• Survival and cause of death
• Incidence and type of second cancers

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

Descriptive Information

• Brief Title: PET Scan in Planning Treatment in Patients Undergoing Combination Chemotherapy For Stage IA or Stage IIA Hodgkin Lymphoma
• Official Title: A Randomised Phase III Trial to Determine the Role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin's Disease

Brief Summary

RATIONALE: A PET scan may help doctors learn how the cancer responded to combination chemotherapy and whether radiation therapy is also required.

PURPOSE: This randomized phase III trial is studying giving a PET scan to see how well it works in deciding whether patients who have received combination chemotherapy for stage IA or stage IIA Hodgkin lymphoma also need radiation therapy.

Detailed Description

OBJECTIVES:

• Determine whether patients with stage IA or IIA Hodgkin lymphoma who have a negative fludeoxyglucose F 18 positron emission tomography (FDG-PET) imaging after 3 courses of chemotherapy comprising doxorubicin hydrochloride, bleomycin sulfate, vinblastine, and dacarbazine (ABVD) require consolidation radiotherapy (to areas of previous involvement) in order to delay or prevent disease progression.

OUTLINE: Patients receive doxorubicin hydrochloride IV, bleomycin sulfate IV, vinblastine IV, and dacarbazine IV (ABVD) on days 1 and 15. Treatment repeats every 28 days for 3 courses. On day 15 of the third course of chemotherapy, patients undergo a CT scan of the neck, thorax, abdomen and pelvis. Patients with nonresponsive disease or progressive disease are removed from the study. Patients who achieve response undergo fludeoxyglucose F 18 positron emission tomography (FDG-PET). Patients with a positive FDG-PET scan receive an additional course of ABVD and undergo involved field radiotherapy. Patients with a negative FDG-PET scan are randomized to 1 of 2 treatment arms.

• Arm I: Within 6 weeks after completion of course 3 of chemotherapy, patients undergo involved field radiotherapy to disease areas.
• Arm II: Patients receive no further treatment. After completion of study therapy, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma

Intervention

• Radiation: Involved Field Radiotherapy
  IFRT 30Gy delivered in daily fractions of 1.8 - 2.0Gy
• Other: No further treatment

Study Arms

• Active Comparator: Arm I
  Within 6 weeks after completion of course 3 of chemotherapy, patients undergo involved field radiotherapy to disease areas.
  Intervention: Radiation: Involved Field Radiotherapy
• Experimental: Arm II
  Patients receive no further treatment.
  Intervention: Other: No further treatment

Publications *

• Cutter DJ, Ramroth J, Diez P, Buckle A, Ntentas G, Popova B, Clifton-Hadley L, Hoskin PJ, Darby SC, Radford J, Illidge T. Predicted Risks of Cardiovascular Disease Following Chemotherapy and Radiotherapy in the UK NCRI RAPID Trial of Positron Emission Tomography-Directed Therapy for Early-Stage Hodgkin Lymphoma. J Clin Oncol. 2021 Nov 10;39(32):3591-3601. doi: 10.1200/JCO.21.00408. Epub 2021 Aug 13.
• Illidge TM, Phillips EH, Counsell N, Pettengell R, Johnson PWM, Culligan DJ, Popova B, Clifton-Hadley L, McMillan A, Hoskin P, Barrington SF, Radford J. Maximum tumor diameter is associated with event-free survival in PET-negative patients with stage I/IIA Hodgkin lymphoma. Blood Adv. 2020 Jan 14;4(1):203-206. doi: 10.1182/bloodadvances.2019001023.
• Barrington SF, Phillips EH, Counsell N, Hancock B, Pettengell R, Johnson P, Townsend W, Culligan D, Popova B, Clifton-Hadley L, McMillan A, Hoskin P, O'Doherty MJ, Illidge T, Radford J. Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study. J Clin Oncol. 2019 Jul 10;37(20):1732-1741. doi: 10.1200/JCO.18.01799. Epub 2019 May 21.
• Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, Wimperis J, Culligan D, Popova B, Smith P, McMillan A, Brownell A, Kruger A, Lister A, Hoskin P, O'Doherty M, Barrington S. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015 Apr 23;372(17):1598-607. doi: 10.1056/NEJMoa1408648.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 9, 2013): 602
• Original Estimated Enrollment (submitted: July 21, 2009): 400
• Estimated Study Completion Date: December 2028
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin Lymphoma

  • Stage IA or IIA disease

    • No stage IA Hodgkin lymphoma with no clinical or CT evidence of disease after diagnostic biopsy

  • Above the diaphragm with no mediastinal bulk, defined as maximum transverse diameter of mediastinal mass

    • Internal thoracic diameter at level of D5/6 interspace > 0.33
  • Bulky disease at other sites, defined as nodal mass with transverse diameter ≥ 10 cm allowed

PATIENT CHARACTERISTICS:

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for ≥ 6 months
• No prior malignancy except appropriately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
• No severe underlying illness considered to make the trial therapy hazardous (i.e., severe heart disease or lung fibrosis)
• Willing to travel to the nearest PET scan center
• Able to comply with protocol follow-up arrangements

PRIOR CONCURRENT THERAPY:

• No prior treatment for Hodgkin lymphoma
• No contraindications to chemotherapy or radiotherapy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT00943423
• Other Study ID Numbers: 03_DOG05_07; CHNT-RAPID; ISRCTN99811594; EU-20931
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University College, London
• Original Responsible Party: Not Provided
• Current Study Sponsor: University College, London
• Original Study Sponsor: The Christie NHS Foundation Trust
• Collaborators: The Christie NHS Foundation Trust

Investigators

• Principal Investigator: John Radford, MD; The Christie NHS Foundation Trust

• PRS Account: University College, London
• Verification Date: November 2023