Trial Comparing Two Protocols of re Irradiation in an Irradiated Area for Carcinoma of the Upper Aerodigestive Tract (JANORL2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Gustave Roussy, Cancer Campus, Grand Paris
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier:
NCT01211938
First received: September 29, 2010
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

Patients will be randomised after surgery, provided surgery is macroscopically adequate, that there is a flap of tissue protecting the vascular axis and that wound healing allows reirradiation to begin less than 8 weeks after surgery.Reirradiation will begin in the two arms less than 8 weeks after surgery in the irradiated area. The reirradiated volume : tumour bed + a safety margin of < 2 cm with immediate protection of bone marrow. This volume should be jointly defined by the radiotherapist and the surgeon. During reirradiation, 60 Gy will be delivered in the two arms but will last 11 weeks in the reference arm and 5 weeks in the investigational arm.Acute toxicity (NCI-CTCAE) will be evaluated at the end of reirradiation and at 6 months from randomization (first follow-up consultation)


Condition Intervention Phase
Squamous Cell Carcinoma
Radiation: single-fraction radiotherapy with concomitant 5FU and Hydrea
Radiation: hyperfractionated radiotherapy with concomitant Cetuximab
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase 2 Trial Evaluating the Acute Toxicity of Two Protocols of Reirradiation After Surgery in an Irradiated Area for Carcinoma of the Upper Aerodigestive Tract - Single-fraction Radiotherapy With Concomitant 5FU and Hydrea Administered Every Other Week - Continuous Hyperfractionated Radiotherapy With Concomitant Cetuximab

Resource links provided by NLM:


Further study details as provided by Gustave Roussy, Cancer Campus, Grand Paris:

Primary Outcome Measures:
  • Acute toxicity requiring an interruption of radiotherapy for more than 2 weeks [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Overall survival at 3 years and loco-regional control at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 384
Study Start Date: April 2010
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: single-fraction radiotherapy with concomitant 5FU and Hydrea
six 5-day cycles with a 9-day rest period between each cycle (split course). Each cycle includes : a single-fraction at a dose of 2 Gy per session for 5 sessions, combined with 5FU (800 mg/m2/day) and Hydrea (500 mg x 3/day) over the 5 days of the cycle. The total dose of radiotherapy is therefore 60 Gy delivered over 11 weeks.
Radiation: single-fraction radiotherapy with concomitant 5FU and Hydrea
single-fraction radiotherapy with concomitant 5FU and Hydrea
Experimental: hyperfractionated radiotherapy with concomitant Cetuximab
Bifractionated radiotherapy at a dose of 1.2 Gy per session at a rate of 2 sessions per day, at least 6h apart, 5 days per week over 5 weeks, without a split course, combined with Cetuximab. The total dose of radiotherapy is 60 Gy delivered over 5 weeks. Cetuximab (ErbituxÒ) is to be administered in a 2-hour IV infusion at a dose of 400 mg/m2, 8 days before the start of radiotherapy, then in a 1-hour infusion at a dose of 250 mg/m2 on days 1, 8, 15, 22 and 29 of radiotherapy.
Radiation: hyperfractionated radiotherapy with concomitant Cetuximab
hyperfractionated radiotherapy with concomitant Cetuximab

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recurrent or second upper aerodigestive tract carcinoma in an area previously irradiated at a dose of >= 50 Gy
  • Squamous cell carcinoma
  • No grade III or IV sequels linked to the first radiation therapy (excepted radiation sequels of salivary glands)
  • Relapse or second carcinoma (clinically invasive and/or lymph node recurrence >= 3 cm and/or the association of a local and lymph node recurrence
  • Oral cavity, pharynx, larynx (if rT4), cervical region (if >3cm)
  • No distant metastases confirmed by chest CT scan, abdominal ultrasound (or CT scan) in case of abnormal liver function, and bone scintigraphy in case of local symptoms
  • Surgery in the previously irradiated region allowing a macroscopically adequate resection
  • Surgery and vascular protection with a myocutaneous or free flap
  • Interval > = 6 months between the end of the first radiation treatment and surgery in the previously irradiated area
  • Wound healing allowing reirradiation within an interval of 8 weeks after surgery in the previouly irradiated area.
  • No participation in a clinical trial during the 30 days preceding inclusion
  • Age between 18 et 70 years.
  • Performance Status 0 or 1 according to WHO criteria.
  • Hematological function : neutrophils * 2 x 106/l, platelets : * 100 x 106/l, hemoglobin : * 10 g/dl (or 6.2 mmol/l)
  • Liver function : total bilirubin (normal) ; ASAT (SGOT) and ALAT (SGPT) * 2.5 * upper limit of normal (ULN) in each centre ; alkaline phosphatases * 5 * ULN. Patients whose ASAT or ALAT levels > 1.5 * ULN associated with alkaline phosphatases * 2.5 * ULN are not eligible for the trial
  • Renal function : serum creatinine * 120 *mol/l (1.4 mg/dl) ; if creatinine level is > 120 *mol/l, creatinine clearance should be * 60 ml/min.
  • Written consent of participants

Exclusion Criteria:

  • Superficial recurrence not associated with a lymph node relapse, isolated lymph node recurrence measuring less than 3 cm
  • Distant metastases
  • Grade 3 or 4 sequels of first radiation therapy (excepted salivary gland sequels)
  • Macroscopically inadequate surgery
  • Delay in wound healing obliging reirradiation to be postponed beyond 8 weeks.
  • > Grade 3 Toxicity induced by chemotherapy administered during a previous treatment
  • Hypersensitivity to Erbitux
  • Concomitant severe comorbidities (non exhaustive list)
  • Unstable cardiac comorbidity in spite of treatment.
  • Neurological or psychiatric history such as dementia, convulsions.
  • Severe uncontrolled infection
  • Obstructive bronchopneumopathy which required hospitalisation during the year preceding inclusion.
  • Factors (psychological, familial, social or geographic) likely to hinder patient compliance with the study protocol and follow-up are considered exclusion criteria. These factors should be discussed with the patient before enrollment in the trial
  • Women who are pregnant, breast-feeding or of birthgiving age without effective contraception
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01211938

Contacts
Contact: François JANOT, MD 00 33 42114590 francois.janot@igr.fr
Contact: Sandrine LANCEREAU 00 33 1 42116261 sandrine.lancereau@igr.fr

Locations
France
Institut Gustave Roussy Recruiting
Villejuif, France, 94800
Contact: François JANOT, MD    00 33 1 42114590    francois.janot@igr.fr   
Contact: Sandrine LANCEREAU    00 33 1 42116261    sandrine.lancereau@igr.fr   
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
Ministry of Health, France
  More Information

Additional Information:
No publications provided

Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT01211938     History of Changes
Other Study ID Numbers: CSET 1542-JANORL2, 2009-017047-34
Study First Received: September 29, 2010
Last Updated: March 31, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Gustave Roussy, Cancer Campus, Grand Paris:
phase II/III
upper aerodigestive tract carcinoma
re irradiation
Recurrent or second upper aerodigestive tract carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Fluorouracil
Cetuximab
Hydroxyurea
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antisickling Agents
Hematologic Agents
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014