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Comparison of Two Concomitant Administration of RT With Cisplatin in Standard Infusion or Fractional Infusion (CisFRad)

Primary Purpose

Squamous Cell Carcinoma of the Head and Neck

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Split Cisplatin
Cisplatin
Radiotherapy
Sponsored by
Groupe Oncologie Radiotherapie Tete et Cou
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Squamous cell carcinoma of head and neck cancer stage III or IV: oral cavity, oropharynx, larynx or hypopharynx.
  • Patient non-operated and / or inoperable for reasons of non extirpabilité, local and regional expansion, general state or medical condition Or
  • Patient operated within 8 weeks before radiation therapy with a high risk of recurrence: unsatisfactory surgical margins (R1) and / or lymph node involvement with capsular rupture.
  • Activity Index according to WHO ≤ 2
  • Age ≤ 70 years
  • Ventricular ejection fraction left retained> 50%
  • Renal allowing the administration of cisplatin: creatinine clearance> 60 ml / min (Cockroft formula)
  • Hematologic function allowing administration of CT: PNN> 1500, Pl> 100000, Hb> 9g
  • Satisfactory Liver function: SGOT and SGPT <3N; total bilirubin <20 mg / dL; INR <1.5; albumin> 30 g / l
  • Stomatological care adapted
  • Signature of informed consent
  • Bilateral neck irradiation Indication
  • Women and men of reproductive age should have accepted a medically effective contraception during the treatment period and at least 6 months after discontinuation of study treatment. If pregnancy is declared by a patient or partner of a patient, it must be followed for know the evolution of pregnancy.

Exclusion Criteria:

  • Cancers of the nasopharynx, sinus or nasal cavities
  • Histology other than squamous
  • Presence of distant metastases
  • Prior systemic chemotherapy (neoadjuvant)
  • Other concomitant cancer therapies
  • Presence of infection requiring the use of IV antibiotics including tuberculosis and HIV infection
  • Coronary insufficiency, cardiac arrhythmias, uncontrolled or symptomatic heart failure
  • Uncontrolled hypertension
  • Peripheral neuropathy grade> 1
  • Vaccination against yellow fever and phenytoin recent or planned
  • History of cancer within 5 years prior to trial entry other than cutaneous basal cell carcinoma in situ or cervical
  • Pregnant woman capable of being or during lactation
  • Persons deprived of liberty, under guardianship
  • Inability to submit to medical monitoring testing for geographical, social or psychic
  • Unilateral cervical radiotherapy Indication

Sites / Locations

  • Centre Paul Strauss

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Split Cisplatin and radiotherapy

Cisplatin and radiotherapy

Arm Description

25 mg/m2/day IV infusion at D1 to D4, at D22 to D25, at D43 to D46 during the radiotherapy

100 mg/m2/day IV infusion at D1, D22 and D43 during the radiotherapy

Outcomes

Primary Outcome Measures

cumulative dose of administered cisplatin in each arm
cisplatin dose amount received at each cycle

Secondary Outcome Measures

Frequency of toxicities
Assessment of toxicity in accordance with NCI-CTC-AE 4.03
Maximum Platine Concentration [Cmax],
Blood sample
Area Under the Curve [AUC] of platine
Blood sample
Values of Neutrophil Gélatinase-associated Lipocalin (NGAL)
Urinary sample
Doses of radiation
total dose received
Duration of radiation
Interruption of radiotherapy due to toxicity
Loco-regional failure rate
Delay between the date of randomisation and the occurrence of a recurrence
overall survival
Delay between the date of randomization and death

Full Information

First Posted
January 17, 2017
Last Updated
March 10, 2022
Sponsor
Groupe Oncologie Radiotherapie Tete et Cou
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1. Study Identification

Unique Protocol Identification Number
NCT03330249
Brief Title
Comparison of Two Concomitant Administration of RT With Cisplatin in Standard Infusion or Fractional Infusion
Acronym
CisFRad
Official Title
Phase II Randomized Trial Comparating Two Concomitant Administration of Radiotherapy With Cisplatin in Patients With Not Operated or Inoperable HNSCC or With Recurrence High Risk in Adjuvant Postoperative Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
December 3, 2015 (Actual)
Primary Completion Date
May 10, 2021 (Actual)
Study Completion Date
May 10, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Groupe Oncologie Radiotherapie Tete et Cou

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The general aim is to compare the cumulative dose of cisplatin administered concomitantly with radiotherapy in reference arm A (cisplatin 100 mg / m2 day 1 every 21 days) and in the experimental arm B (Cisplatin split 25 mg / m2 / J D1 to D4 all 21 days).
Detailed Description
The standard treatment for squamous cell carcinoma of the head and neck locally advanced non-operated or non-operable is a combination of radiotherapy and concomitant chemotherapy. Indeed, the meta-analysis MACH showed for RT / CT associations an absolute survival benefit of 8% compared with radiotherapy alone. Cisplatin delivered optimally, ie at a dose of 100 mg / m2 on day 1, D22 and D43 of radiotherapy is as effective as combinations of cisplatin and 5-fluorouracil. In post operative, treatment of high risk recurrence forms by Cisplatin, concomitantly with radiotherapy, also increases local control and overall survival. However, it is an association whose toxicity is significant. The usual limiting toxicities were mucositis, dysphagia, nausea and vomiting with malnutrition and biologically kidney failure and myelotoxicity. Only 2/3 of the patients receive 3 cycles of cisplatin initially programmed. As shown in the RTOG 0129 trial, the number of cycles of cisplatin and thus the cumulative dose of cisplatin administered concurrently with radiation therapy, significantly influences the locoregional control, progression free survival and overall survival. One method of reducing the toxicity and thereby, increase the cumulative dose, would be to split the administration of cisplatin. Moreover, the efficacy of Cisplatin, which only the free fraction is active, seems correlated with AUC that peak plasma which would in turn responsible for toxicity. The completion of a pharmacokinetic study comparing the AUC and Cmax obtained with cisplatin 100 mg / m2 and cisplatin fractionated is essential. Finally, the limiting renal toxicity induced by cisplatin is currently diagnosed using the creatinine clearance. The Neutrophil gelatinase-associated lipocalin (NGAL) urinary is a new diagnosis and prognosis marker of renal impairment following treatment with cisplatin. However, further studies are needed to validate its clinical utility.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
124 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Split Cisplatin and radiotherapy
Arm Type
Experimental
Arm Description
25 mg/m2/day IV infusion at D1 to D4, at D22 to D25, at D43 to D46 during the radiotherapy
Arm Title
Cisplatin and radiotherapy
Arm Type
Active Comparator
Arm Description
100 mg/m2/day IV infusion at D1, D22 and D43 during the radiotherapy
Intervention Type
Drug
Intervention Name(s)
Split Cisplatin
Other Intervention Name(s)
Cisplatin infusion
Intervention Description
25 mg/m2/day IV infusion at D1 to D4, at D22 to D25, at D43 to D46 during the radiotherapy.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Cisplatin infusion
Intervention Description
100 mg/m2/day IV infusion at D1, D22 and D43 during the radiotherapy.
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Other Intervention Name(s)
Radiotherapy IMRT with possibly integrated boost
Intervention Description
70 Gy in 35 fractions of 2 Gy in non-operated patients and 66 Gy in 33 fractions in post-operative.
Primary Outcome Measure Information:
Title
cumulative dose of administered cisplatin in each arm
Description
cisplatin dose amount received at each cycle
Time Frame
36 months after the end of treatment
Secondary Outcome Measure Information:
Title
Frequency of toxicities
Description
Assessment of toxicity in accordance with NCI-CTC-AE 4.03
Time Frame
Every week during treatment and every 3 months after treatment up to 3 years
Title
Maximum Platine Concentration [Cmax],
Description
Blood sample
Time Frame
Cycle 1 before infusion, 90 min, 180 min,210 min, 270 min, 360 min and 420 min after the beginning of infusion in comparator arm and before infusion, 30 min, 45 min,75 min, 135 min, 225 min in experimental arm at Day 1 and Day 4
Title
Area Under the Curve [AUC] of platine
Description
Blood sample
Time Frame
Cycle 1 before infusion, 90 min, 180 min, 210 min, 270 min, 360 min and 420 min after the beginning of infusion in comparator arm and before infusion, 30 min, 45 min, 75 min, 135 min, 225 min in experimental arm at Day 1 and Day 4
Title
Values of Neutrophil Gélatinase-associated Lipocalin (NGAL)
Description
Urinary sample
Time Frame
Baseline and 24hour after infusion of cisplatin in comparator arm and 24hour after the last infusion of cisplatin in experimental arm
Title
Doses of radiation
Description
total dose received
Time Frame
7 weeks after the beginning of radiotherapy
Title
Duration of radiation
Description
Interruption of radiotherapy due to toxicity
Time Frame
7 weeks after the beginning of radiotherapy
Title
Loco-regional failure rate
Description
Delay between the date of randomisation and the occurrence of a recurrence
Time Frame
36 months after the end of randomization
Title
overall survival
Description
Delay between the date of randomization and death
Time Frame
36 months after the end of randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Squamous cell carcinoma of head and neck cancer stage III or IV: oral cavity, oropharynx, larynx or hypopharynx. Patient non-operated and / or inoperable for reasons of non extirpabilité, local and regional expansion, general state or medical condition Or Patient operated within 8 weeks before radiation therapy with a high risk of recurrence: unsatisfactory surgical margins (R1) and / or lymph node involvement with capsular rupture. Activity Index according to WHO ≤ 2 Age ≤ 70 years Ventricular ejection fraction left retained> 50% Renal allowing the administration of cisplatin: creatinine clearance> 60 ml / min (Cockroft formula) Hematologic function allowing administration of CT: PNN> 1500, Pl> 100000, Hb> 9g Satisfactory Liver function: SGOT and SGPT <3N; total bilirubin <20 mg / dL; INR <1.5; albumin> 30 g / l Stomatological care adapted Signature of informed consent Bilateral neck irradiation Indication Women and men of reproductive age should have accepted a medically effective contraception during the treatment period and at least 6 months after discontinuation of study treatment. If pregnancy is declared by a patient or partner of a patient, it must be followed for know the evolution of pregnancy. Exclusion Criteria: Cancers of the nasopharynx, sinus or nasal cavities Histology other than squamous Presence of distant metastases Prior systemic chemotherapy (neoadjuvant) Other concomitant cancer therapies Presence of infection requiring the use of IV antibiotics including tuberculosis and HIV infection Coronary insufficiency, cardiac arrhythmias, uncontrolled or symptomatic heart failure Uncontrolled hypertension Peripheral neuropathy grade> 1 Vaccination against yellow fever and phenytoin recent or planned History of cancer within 5 years prior to trial entry other than cutaneous basal cell carcinoma in situ or cervical Pregnant woman capable of being or during lactation Persons deprived of liberty, under guardianship Inability to submit to medical monitoring testing for geographical, social or psychic Unilateral cervical radiotherapy Indication
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian BOREL, MD
Organizational Affiliation
Centre Paul Strauss
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Paul Strauss
City
Strasbourg
ZIP/Postal Code
67065
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

Comparison of Two Concomitant Administration of RT With Cisplatin in Standard Infusion or Fractional Infusion

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