Trial Evaluating Adapted Chemotherapy in Patients With Squamous Carcinoma (TPFmORL)

A Phase II Randomized Trial, Non Comparative, Evaluating Chemotherapy Associated Cisplatin, 5-fluorouracil and Docetaxel at Adapted Doses in Patients With Locally Advanced Squamous Cell Carcinoma

The objective of this study is to evaluate the efficacity of the combination of cisplatin-5-FU and docetaxel in adapted doses in term of response to treatment without toxicity

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Study Overview

• Status: Active, not recruiting
• Conditions: Cancer of Head and Neck
• Intervention / Treatment: Drug: Docetaxel; Drug: Cisplatin; Drug: Fluoro Uracil

Detailed Description

After explaining the treatment modalities, having read and explained the information letter to them, patients who have signed the consent to participate in the trial and who meet the inclusion criteria will be enrolled and randomized in the trial .

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69008
    • Centre Leon Berard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically proven squamous cell carcinoma of the head and neck from one or more of the following primary sites: oral cavity, oropharynx, hypopharynx or larynx, lymphadenopathy without front door

2. Inoperable tumor or tumor whose surgery would be multilating.

   The non-operability criteria are:

   • Technically impossible resection: fixation / invasion of the tumor at the base of the skull or at the cervical vertebrae, nasopharynx involved, lymph nodes
   • Medical selection based on low surgical curability. This category includes all T3-T4 and all N2-N3 (AJCC 8th edition, June 2018)
   • Medical selection based on an organ preservation strategy
3. Patient not previously treated for ORL cancer
4. Age > 18 and < 75 years
5. PS 0 or 1 according to WHO
6. At least one lesion measurable according to the RECIST 1.1 criteria

7. Patient who can receive TPF according to the following criteria:

   • Adequate hematological function: neutrophils ³ 1.5 x 109 / l, platelets *100 x 109 / l, hemoglobin 10 g / dl (or 6.2 mmol / l)
   • Adequate renal function: calculated creatinine clearance (Cockroft & Gault) or measured ³ 60 ml / min.
   • Adequate liver function: normal total bilirubin; ASAT and ALAT less than or equal to 1.5 ´ LNS; PAL less than or equal to 2.5 X LNS
   • Grade <2 peripheral neuropathy according to NCI CTCAE v5.0
   • No clinical impairment of hearing function
   • For patients aged 71 to 74, PS at 0 and considered non-geriatrically fragile (G8 questionnaire and multidimensional assessments proposed by the GERICO group (ADL, MMSE, GDS scale, nutrition, motor skills and balance, geographic and personal situation and assessments) thymic))
8. Estimated life expectancy greater than or equal to 3 months
9. Weight loss of less than 10% during the 3 months before randomization
10. Patient understanding French and able to complete quality of life questionnaires
11. Patient having given written consent before any specific protocol procedure
12. Affiliation to a social security scheme or beneficiary of such a scheme
13. Women of childbearing potential and sexually active men agreeing to use effective contraceptive methods for the duration of treatment and at least 6 months after the last administration of study treatments
14. Patient agrees not to donate sperm for the duration of the treatment and at least 6 months after the last administration of the study treatments
15. Absence of deficiency in dihydropyrimidine dehydrogenase activity determined by uracilemia assay (Uracilemia < 16 ng/mL)

Exclusion Criteria:

1. Cancers of the nasopharynx, sinuses or nasal cavities, and any histology other than squamous cell carcinoma
2. Vaccination against recent or planned yellow fever
3. Known deficiency in dihydropyrimidine dehydrogenase (DPD) or determined by the determination of uricemia.
4. History of other cancer except in situ cervical cancer or controlled basal cell carcinoma. Patients in remission from cancer treated more than 3 years ago are eligible. Patients treated by surgery alone for ORL cancer in the previous 3 years are eligible.
5. Previous treatment of an ORL cancer by chemotherapy or radiotherapy. Patients treated by surgery alone for ORL cancer in the previous 3 years are eligible).
6. Presence of distant metastasis.
7. Participation in a therapeutic trial in the 30 days preceding randomization
8. Concomitant anticancer treatment
9. Patient under chronic treatment (3 months) with corticosteroid whose daily dosage is 10 mg / day of methylprednisolone or equivalent

10. Other existing serious medical pathologies (non-exhaustive list):

    • Uncontrolled cardiac pathology despite adequate treatment
    • Myocardial infarction in the 6 months preceding randomization
    • Neurological or psychiatric history such as dementia, convulsions
    • Active infection
    • Significant gastrointestinal abnormalities, including those that require parenteral nutrition, active peptic ulcer, and history of surgeries affecting absorption
    • Obstructive pulmonary disease requiring hospitalization in the year preceding randomization
    • Uncontrolled type II diabetes or other corticosteroid contraindications.
    • Moderate or severe eczema
11. Known hypersensitivity to docetaxel, cisplatin 5FU or one of their excipients.
12. Intended concomitant use of phenytoin, carbamazepine, barbiturates or rifampicin
13. Presence, upon selection, of psychological, family, social or geographic factors likely to influence the patient's compliance with the study and monitoring protocol.
14. Pregnant or lactating woman
15. Patient (male or female) of reproductive age who is unable or unwilling to take adequate contraceptive measures during treatment and up to 6 months after the last treatment is administered.
16. Persons deprived of their liberty, under guardianship or curatorship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TPF (docetaxel, cisplatine, 5-FU); Docetaxel, cisplatine, 5-FU administered, every 3 weeks for a total of 3 cycles	Drug: Docetaxel; Docetaxel 75 mg/m² administered at D1 of each cure, every 3 weeks by intravenous infusion in 1 hour; Drug: Cisplatin; cisplatine 75 mg/m² administered at D1 of each cure, every 3 weeks by intravenous infusion in 1 hour; Drug: Fluoro Uracil; 750 mg/m²/j administered continuously at D1 to D5 of each cure, every 3 weeks by intravenous infusion ( so 120 hours)
Experimental: TPFm (docetaxel, cisplatine, 5-FU) modifié; Docetaxel, cisplatine, 5-FU administered, every 2 weeks for a total of 6 cycles	Drug: Docetaxel; Docetaxel 75 mg/m² administered at D1 of each cure, every 3 weeks by intravenous infusion in 1 hour; Drug: Cisplatin; cisplatine 75 mg/m² administered at D1 of each cure, every 3 weeks by intravenous infusion in 1 hour; Drug: Fluoro Uracil; 750 mg/m²/j administered continuously at D1 to D5 of each cure, every 3 weeks by intravenous infusion ( so 120 hours)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacity of combination of TPFm	Success rate of patients at 8 weeks	8 weeks after the end of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The time from date of randomization to date of death due to any cause	3 months after the end of treatment
Progression free survival	The time from date randomization to date of first evidence of progression	3 months after the end of treatment
incidence of local and/or locorégional failure		3 months after the end of treatment
Laryngeal preservation		3 months after the end of treatment
incidence of distant metastatic failure	The time from the date of randomization and the date of first evidence of metastatic progression, or the date of death, whatever the cause	3 months after the end of treatment
Toxicities of complementary treatment to induction tretatment	Rate of patients who received the whole of complementary treatment	3 months after the end of treatment
QLQ-C30 questionnaires	These questionnaires assess the impact of the desease and treatment on tthe patient's life	8 weeks, 6 months (3 months after the end of treatment) and 24 months after the end of treatment
QLQ-H&N35 questionnaires	These questionnaires assess the impact of the desease and treatment on tthe patient's life	8 weeks, 6 months (3 months after the end of treatment) and 24 months after the end of treatment

Collaborators and Investigators

• Sponsor: Groupe Oncologie Radiotherapie Tete et Cou
• Collaborators: Centre Leon Berard

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: April 10, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: ORL cancer without front door, TPFm, inoperable tumor
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Fluorouracil
• Other Study ID Numbers: GORTEC 2019-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No