Treatment of Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

NCT01086826 | Completed Phase 3

• 1 other identifier: H&N07
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 60

Brief Summary

This is a randomized multicenter open label phase III factorial trial evaluating the 3 years OS in patients with locally advanced squamous cell carcinoma of head and neck treated with locoregional treatment (radiotherapy plus concomitant chemotherapy or cetuximab) with or without neoadjuvant chemotherapy.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• overall survival

  overall survival defined as the time from the date of randomization to the date of death from any cause.

  3 years

Secondary Outcomes (1)

• progression free survival

  3 years

Study Arms (4)

RT+CDDP/5-FU

ACTIVE COMPARATOR

RT: Tumor: 70 Gy (2 Gy x1/day, 5 days per week for 7 weeks) Lymph nodes: at least 50 Gy (2 Gy x1/day, 5 days per week for 6 weeks) CDDP: 20 mg/m2/day as 30 minutes IV infusion from day 1 to day 4 5-FU 800 mg/m2/day for 4 will be administered as continuos iv infusion Both drugs will be administered during weeks 1 and 6 of irradiation, starting from day 1 of radiotherapy.

Drug: RT+CDDP/5-FU

RT+CETUXIMAB

EXPERIMENTAL

RT: Tumor: 70 Gy (2 Gy x1/day, 5 days per week for 7 weeks) Lymph nodes: at least 50 Gy (2 Gy x1/day, 5 days per week for 6 weeks) CETUXIMAB: Cetuximab 400 mg/m2 as first dose, 7 days before the beginning of radiotherapy as 120 minutes IV infusion. Subsequent doses of 250 mg/ m2 will be administered as 60 minutes IV infusion, weekly, for 7 times.

Drug: RT+CETUXIMAB

INDUCTION CTx(TPF)+(RT+CDDP/5-FU)

ACTIVE COMPARATOR

INDUCTION CTx(TPF): DOCETAXEL: 75 mg/m², 1 hour IV infusion, Day and every 3 weeks CISPLATIN: 80mg/m², intravenous infusion over 30-minute to 3 hours,Day 1 immediately after docetaxel administration and then every 3 weeks 5-FU 800 mg/m²/day, 24 hour continous infusion over 4 days, Day 1 after the end of cisplatin infusion, and every 3 weeks. RT: Tumor: 70 Gy (2 Gy x1/day, 5 days per week for 7 weeks) Lymph nodes: at least 50 Gy (2 Gy x1/day, 5 days per week for 6 weeks) CDDP: 20 mg/m2/day as 30 minutes IV infusion from day 1 to day 4 5-FU 800 mg/m2/day for 4 will be administered as continuos iv infusion

Drug: INDUCTION CTx(TPF)+(RT+CDDP/5-FU)

INDUCTION CTx(TPF)+(RT+CETUXIMAB)

EXPERIMENTAL

DOCETAXEL: 75 mg/m², 1 hour IV infusion, Day and every 3 weeks CISPLATIN: 80mg/m², intravenous infusion over 30-minute to 3 hours,Day 1 immediately after docetaxel administration and then every 3 weeks 5-FU 800 mg/m²/day, 24 hour continous infusion over 4 days, Day 1 after the end of cisplatin infusion, and every 3 weeks. RADIOTHRAPY: Tumor: 70 Gy (2 Gy x1/day, 5 days per week for 7 weeks) Lymph nodes: at least 50 Gy (2 Gy x1/day, 5 days per week for 6 weeks) CETUXIMAB: Cetuximab 400 mg/m2 as first dose, 7 days before the beginning of radiotherapy as 120 minutes IV infusion. Subsequent doses of 250 mg/ m2 will be administered as 60 minutes IV infusion, weekly, for 7 times.

Drug: INDUCTION CTx(TPF)+(RT+CETUXIMAB)

Interventions

RT+CDDP/5-FU DRUG

RT=70 Gy (2 Gy x1/day, 5 days per week for 7 weeks) CDDP: 20 mg/m2/day as 30 minutes IV infusion from day 1 to day 4 5-FU: 800 mg/m2/day for 4 days Both drugs will be administered during weeks 1 and 6 of irradiation, starting from day 1 of radiotherapy.

Also known as: Radiotherapy, Cisplatin, 5-fluoruracil

RT+CDDP/5-FU

RT+CETUXIMAB DRUG

RT= 70 Gy (2 Gy x1/day, 5 days per week for 7 weeks) Cetuximab= 400 mg/m2 as first dose.Subsequent doses of 250 mg/ m2, weekly, for 7 times.

Also known as: Radiotherapy, Cetuximab

RT+CETUXIMAB

INDUCTION CTx(TPF)+(RT+CDDP/5-FU) DRUG

INDUCTION CTx(TPF):docetaxel 75 mg/m² + CDDP 80mg/m² + 5-FU 800 mg/m²/day from day 1 to day 4 will begin after the end of cisplatin infusion on day 1.Every 3 weeks. concomitant CTx= CDDP 20 mg/m2/day + 5-FU 800 mg/m2/day RT= 70 Gy(2 Gy x1/day, 5 days per week for 7 weeks)

Also known as: Docetaxel. Cisplatin, 5-fluoruracil, Radiotherapy

INDUCTION CTx(TPF)+(RT+CDDP/5-FU)

INDUCTION CTx(TPF)+(RT+CETUXIMAB) DRUG

INDUCTION CTx(TPF):docetaxel 75 mg/m² + CDDP 80mg/m² + 5-FU 800 mg/m²/day from day 1 to day 4 will begin after the end of cisplatin infusion on day 1.Every 3 weeks. RT= 70 Gy(2 Gy x1/day, 5 days per week for 7 weeks) CETUXIMAB= 400 mg/m2 as first dose. Subsequent doses of 250 mg/ m2, weekly, for 7 times.

Also known as: Docetaxel. Cisplatin, 5-fluoruracil, Radiotherapy, Cetuximab

INDUCTION CTx(TPF)+(RT+CETUXIMAB)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven squamous cell carcinoma of the head and neck.
• Primary tumor sites eligible : oral cavity, oropharynx, hypopharynx Although they are admittedly of squamous cell types, the following tumors will be excluded because of them responsiveness to chemotherapy: tumors of the nasal and paranasal cavities and of the nasopharynx.
• Stage 3 or 4 disease without evidence of distant metastases verified by chest X Ray, abdominal ultrasound, or CT (liver function test abnormalities); bone scan in case of local symptoms.
• At least one uni or bidimensionally measurable lesion.
• Tumor considered inoperable after evaluation by a multidisciplinary team (i.e. a surgeon, a medical oncologist and a radiation oncologist). Criteria for inoperability are:
• technical unresectability: tumor fixation/invasion to base of the skull or cervical vertebrae, involvement of the nasopharynx, and fixed lymph nodes.
• Physician decision based on low surgical curability. This category will include the following:
• i) All T3-4 stages. ii) All N2-3 stages excluding T1 N2. iii) Patients for organ preservation. Reason for inoperability will be recorded in the CRF.
• No previous chemotherapy or radiotherapy for any reason and no previous surgery for SCCHN (other than biopsy) are allowed at time of study entry.
• Age \> 18 years.
• Karnofsky performance status \> 70. (ECOG 0-1) (Appendix II)
• No active alcohol addiction.
• Life expectancy \> 6 months.
• Signed informed consent prior to beginning protocol specific procedures.
• Adequate bone marrow, hepatic and renal functions as evidenced by the following:

You may not qualify if:

• Pregnant or lactating women or women of childbearing potential not using adequate contraception.
• Symptomatic peripheral neuropathy \> grade 2 by NCIC-CTG criteria
• Symptomatic altered hearing \> grade 2 by NCIC-CTG criteria.
• Other serious illnesses or medical conditions including:
• Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry.
• History of significant neurologic or psychiatric disorders including dementia or seizures.
• Active uncontrolled infection.
• Active peptic ulcer.
• Hypercalcemia.
• Chronic obstructive pulmonary disease requiring hospitalization during the year preceding study entry
• History of hypersensitivity reaction to polysorbate 80 (Appendix IV)
• Patients requiring intravenous alimentation.
• Patients who experienced a weight loss of more than 20% of their body weight in the 3 months preceding study entry.
• Concomitant treatment with any other anticancer therapy.
• Participation in a therapeutic clinical trial within 30 days of study entry

Sponsors & Collaborators

• Associazione Volontari Pazienti Oncologici: lead
• Mario Negri Institute for Pharmacological Research: collaborator

Study Sites (60)

Istituto tumori "Giovanni Paolo II" IRCCS

Bari, Bari, 70124, Italy

Location

Ospedale S.Martino

Belluno, Belluno, 32100, Italy

Location

Ospedale "S. Maria Del Prato"

Feltre, Belluno, 32032, Italy

Location

Ospedale Di Treviglio - Caravaggio

Treviglio, Bergamo, 24047, Italy

Location

Ospedale Bellaria Di Bologna

Bologna, Bologna, 40100, Italy

Location

Policlinico S.Orsola-Malpighi

Bologna, Bologna, 40138, Italy

Location

Ospedale "S.Maurizio"

Bolzano, Bolzano, 39100, Italy

Location

Istituto Clinico S.Anna

Brescia, Brescia, 25127, Italy

Location

"Ospedale Businco"

Cagliari, Cagliari, 09121, Italy

Location

Policlinico Universitario

Cagliari, Cagliari, 09121, Italy

Location

A.O Pugliese-Ciaccio

Catanzaro, Catanzaro, 88100, Italy

Location

Ospedale Clinicizzato Di Chieti

Chieti, Chieti, 66100, Italy

Location

A.O. Ospedale Sant'Anna

S.Fermo, Como, 22100, Italy

Location

Ospedale "AUGUSTO MURRI"

Fermo, Fermo, 63023, Italy

Location

A.O.Universitaria

Ferrara, Ferrara, 44100, Italy

Location

IRCCS Casa Sollievo della Sofferenza

S. Giovanni Rotondo, Foggia, 71013, Italy

Location

Azienda Ospedaliera "Alessandro Manzoni"

Lecco, Lecco, 23900, Italy

Location

Ospedale di Macerata

Macerata, Macerata, 62100, Italy

Location

Ospedale "B.Eustachio" - S.Severino

San Severino Marche, Macerata, 62027, Italy

Location

P.O. SAN VINCENZO di Messina

Messina, Messina, 98039, Italy

Location

A.O. Universitaria Di Messina

Messina, Messina, 98151, Italy

Location

Irccs - Ospedale "S. Raffaele"

Milan, Milano, 20132, Italy

Location

"Istituto Europeo di Oncologia"

Milan, Milano, 20141, Italy

Location

"Ospedale San Paolo"

Milan, Milano, 20143, Italy

Location

A.O. Niguarda-Cà Granda

Milan, Milano, 20162, Italy

Location

"A.O. - Policlinico Di Modena"

Modena, Modena, 41100, Italy

Location

H.S. Gerardo dei Tintori

Monza, Moza-Brianza, 20052, Italy

Location

Ospedale Di Camposampiero

Camposampiero, Padova, 35012, Italy

Location

Ospedale Civile di Cittadella

Cittadella, Padova, 35010, Italy

Location

"Istituto Oncologico Veneto"

Padua, Padova, 35100, Italy

Location

Policlinico Universitario di Palermo

Palermo, Palermo, 90100, Italy

Location

Casa di Cura "La Maddalena"

Palermo, Palermo, 90121, Italy

Location

A.O.Universitaria "Ospedale Maggiore"

Parma, Parma, 43121, Italy

Location

Osp. S. Maria della Misericordia

Perugia, Perugia, 06132, Italy

Location

Ospedale Santa Croce Di Fano

Fano, Pesaro-urbino, 61032, Italy

Location

A.O. "Ospedale S. Salvatore"

Pesaro, Pesaro-urbino, 61100, Italy

Location

Ospedale "G. Da Saliceto"

Piacenza, Piacenza, 29121, Italy

Location

Osp. S. Maria Delle Croci

Ravenna, Ravenna, 48100, Italy

Location

A.O. "S.Camillo de' Lellis"

Rieti, Rieti, 02100, Italy

Location

Istituto Nazionale Tumori Regina Elena

Roma, Roma, 00144, Italy

Location

Ospedale S.Pietro "Fatebenefratelli"

Roma, Roma, 00189, Italy

Location

Ospedale Civile Di Sondrio

Sondrio, Sondrio, 23100, Italy

Location

Osp. S.G. Moscati

Taranto, Taranto, 74100, Italy

Location

Ospedale "S. Chiara"

Trento, Trento, 38100, Italy

Location

Ospedale Civile di Castelfranco

Castelfranco Veneto, Treviso, 31033, Italy

Location

Ospedale Ca' Foncello

Treviso, Treviso, 31100, Italy

Location

"Ospedali Riuniti"

Trieste, Trieste, 34100, Italy

Location

Ospedale Civile di Latisana

Latisana, Udine, 33057, Italy

Location

P.O. "S.Antonio Abate"

Tolmezzo, Udine, 33028, Italy

Location

A.O. Santa Maria della Misericordia

Udine, Udine, 33100, Italy

Location

Azienda Ospedaliera Di Circolo

Busto Arsizio, Varese, 21052, Italy

Location

Azienda Ospedaliera "S.Antonio Abate"

Gallarate, Varese, 21013, Italy

Location

Ospedale Di Circolo E Fondazione Macchi

Varese, Varese, 21100, Italy

Location

"Ospedale dell' Angelo"

Mestre, Venezia, 30173, Italy

Location

"Ospedale Civile di Mirano"

Mirano, Venezia, 30035, Italy

Location

Ospedale Civile SS Giovanni e Paolo

Venezia, Venezia, 30174, Italy

Location

"AULSS 21 Mater Salutis"

Legnago, Verona, 37045, Italy

Location

Ospedale Civile Maggiore Borgo Trento

Verona, Verona, 37126, Italy

Location

Ospedale "Boldrini"

Thiene, Vicenza, 36015, Italy

Location

Ospedale civile di Vicenza

Vicenza, Vicenza, 36100, Italy

Location

Related Publications (1)

• Ghi MG, Paccagnella A, Ferrari D, Foa P, Alterio D, Codeca C, Nole F, Verri E, Orecchia R, Morelli F, Parisi S, Mastromauro C, Mione CA, Rossetto C, Polsinelli M, Koussis H, Loreggian L, Bonetti A, Campostrini F, Azzarello G, D'Ambrosio C, Bertoni F, Casanova C, Emiliani E, Guaraldi M, Bunkheila F, Bidoli P, Niespolo RM, Gava A, Massa E, Frattegiani A, Valduga F, Pieri G, Cipani T, Da Corte D, Chiappa F, Rulli E; GSTTC (Gruppo di Studio Tumori della Testa e del Collo) Italian Study Group. Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial. Ann Oncol. 2017 Sep 1;28(9):2206-2212. doi: 10.1093/annonc/mdx299.

  PMID: 28911070 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy; Cisplatin; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Maria Grazia Ghi, MD

  Ospedale SS Giovanni e Paolo - Venezia, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2010
• First Posted: March 15, 2010
• Study Start: March 1, 2008
• Primary Completion: April 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 26, 2015

Record last verified: 2013-06

Locations

IT (60)