Chemo-radiotherapy Versus Radiotherapy in the Treatment of Salivary Glands and Nasal Tumors (IMRT or Protontherapy) (SANTAL)

A Phase III Randomized Study of Chemo-radiotherapy Versus Radiotherapy Alone in the Adjuvant Treatment of Salivary Glands and Nasal Tumors (IMRT or Protontherapy)

A phase III, multicenter, randomized, open-label, french study comparing:

• Arm A : Radiotherapy alone (66 to 70 Gy; 5 fractions/week; 1fraction/day; 2 Gy/fraction) (IMRT or protontherapy)
• Arm B: Radiotherapy (66 to 70 Gy; 5 fractions/week; 1fraction/day; 2 Gy/fraction; IMRT or protontherapy) + concomitant cisplatin 100 mg/m2 IV on day 1 - J22 - 43 (3 cycles)

Study Overview

• Status: Recruiting
• Conditions: HNSCC
• Intervention / Treatment: Radiation: radiotherapy; Drug: Cisplatin

Detailed Description

Carcinomas of the sinuses and the salivary glands are rare. They are heterogeneous in terms of anatomical sites and histology subtypes. For this reason and in the absence of prospective study, their treatment is still largely extrapolated from data of frequent carcinomas of the upper digestive tract. These tumors are most often diagnosed lately. Their treatment is based on a multimodal management of care, with a central place for the surgery and radiotherapy (Proof level Grade C). Despite the advances in surgical techniques, and the addition of radiation therapy, the 5-year overall survival probability does not exceed 65% mainly due to a loco regional development.

In this context, a chemotherapy administered concomitantly to radiotherapy, could increase the efficacy of the locoregional treatment by a radiosensibilization process and regardless of the histology. This point is regularly discussed in multidisciplinary concertation meeting, including bi-monthly national REFCOR meeting (network of French Expertise on rare Cancers of the head and neck). At present, the lack of data brings even to discuss the addition of cisplatin to exclusive irradiation of unresectable or not operable tumors.

No randomized study has been published in this context. The first comparative prospective study addressing the addition of weekly cisplatin to the adjuvant irradiation of salivary, is a phase II randomized study (Radiation Therapy Oncology Group - RTOG 1008) currently enrolling patients in the United States of America.

The Sponsor propose to conduct a phase III randomized study evaluating the impact of the addition of cisplatin to a treatment by radiotherapy in adjuvant setting (≥ 65 Gy) in case of a high risk of recurrence: case of radioresistant histologies (e.g. cystic fibrosis adenoids carcinomas), or case of unfavourable histo-prognostic criteria (incomplete resection, presence of emboli, etc.) in this population.

• Study Type: Interventional
• Enrollment (Estimated): 342
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: François Régis FERRAND, MD; Phone Number: +33 1 78 65 12 49; Email: francoisregis.ferrand@gustaveroussy.fr
• Study Contact Backup: Name: Juliette THARIAT, Prof; Phone Number: +33 02 51 45 50 50; Email: j.thariat@baclesse.unicancer.fr

Study Locations

• France
  • Saint-Mandé, France, 94
    • Recruiting
    • Hopital Bégin
    • Contact: François Régis FERRAND, MD; Email: francoisregisferrand@gmail.com
    • Principal Investigator: Nicolas MEERT, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

- Resected tumors of the sinus or the salivary glands T3-4, N1-3 or T1-2 N0, with overgrown banks or positive margins (< 5 mm)

or

Unresectable or not operable tumors of salivary glands or sinuses

• Carcinomas of the main salivary glands (parotid, submandibular or sublingual glands) and accessories or Malignant sinus tumors with any histological type except melanoma, lymphoma, mesenchymal tumor (sarcoma type), squamous cell carcinoma and nasopharyngeal carcinoma type 1, 2, 3.
• Age ≥ 18 years
• Performance status 0 -2 (WHO criteria)
• For patients ≥ 70 years, the score to the G8 questionnaire must be > 14 with no fall in the previous 12 months or with a geriatric assessment consistent with the administration of chemotherapy
• Estimated life expectancy greater than or equal to 6 months
• Neutrophils > 1.5 x 109/l, platelets > 100 x 109/l, hemoglobin ≥ 9.5 g/dl, bilirubin ≤ 3 x upper normal value (ULN), AST/ALT < 5 ULN, PAL < 3 ULN
• Creatinin Clearance ≥ 60 mL/min (Cockroft formula)
• Adequate cardiac function according to the investigator, compatible with the administration of cisplatin 100 mg/m²
• Affiliation to a social insurance or beneficiary of such a regimen
• Patient having given his written consent signed before any study specific procedure.

Exclusion Criteria:

• History of radiotherapy in the ENT region and/or neoadjuvant chemotherapy for the pathology concerned
• Synchronous metastases
• Contraindications for administration of cisplatin or carboplatin
• Allergy to cisplatin and/or its excipients
• Vaccination against yellow fever, recent or planned
• Administration of phenytoin with prophylactic purpose
• Other cancer, except for cancer in situ of the cervix, skin Carcinoma (except melanoma) or cancer controlled for more than 5 years
• Pregnant, breastfeeding or without birth control woman. Woman having the ability to procreate should have (serum or urinary) negative pregnancy test within 14 days prior to study treatment decision-making. (Men or women) patients should use a reliable contraceptive method throughout the treatment and at least 6 months after the end of chemotherapy.
• Persons deprived of liberty under supervision or under curatorship, or unable to adhere to medical follow-up of the study for geographical, social or psychological reasons.

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: Radiotherapy; Arm A Radiation therapy: 66 to 70 Gy in fractions of 2 Gy, 1 fraction/day, 5 fractions per week. Radiation therapy will be conducted by conformational intensity modulation radiotherapy (IMRT) or protontherapy. Irradiation by 3D conformational radiotherapy can be discussed on a case by case with the Intergroup Coordinator GORTEC.	Radiation: radiotherapy; 66 à 70 Gy per fractions of 2 Gy, 1 fraction/day, 5 fractions/week
Experimental: Radiotherapy + concomitant cisplatin; Arm B Concomitant systemic treatment with cisplatin + radiotherapy According to standard protocol of concomitant cisplatin 100 mg/m2 IV on day 1 - J22 - 43 (3 maximum cycles). Radiation therapy: 66 to 70 Gy in fractions of 2 Gy, 1 fraction/day, 5 fractions per week. Radiation therapy will be conducted by conformational intensity modulation radiotherapy (IMRT) or protontherapy. Irradiation by 3D conformational radiotherapy can be discussed on a case by case with the Intergroup Coordinator GORTEC	Radiation: radiotherapy; 66 à 70 Gy per fractions of 2 Gy, 1 fraction/day, 5 fractions/week; Drug: Cisplatin; intravenous, concomitant to irradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Compare progression-free survival between the 2 treatment arms: radiation therapy alone versus radiochimiotherapy in adjuvant patients treatment operated.	From date of randomization to date of disease progression or death, which occur first, assessed during 62 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Compare the 2 arms of treatment in operated patients in terms of overall survival	From date of randomization to date of death, assessed during 62 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of quality of Life: QLQC30 overall score	Compare quality of life (QLQC30 overall score) between arms	From date of randomization to end of study or death or progression (the first occurred), assessed during 62 months

Collaborators and Investigators

• Sponsor: Groupe Oncologie Radiotherapie Tete et Cou
• Collaborators: National Cancer Institute, France

Publications and helpful links

General Publications

• Joshi NP, Broughman JR. Postoperative Management of Salivary Gland Tumors. Curr Treat Options Oncol. 2021 Feb 9;22(3):23. doi: 10.1007/s11864-021-00820-9.
• Ferrari M, Orlandi E, Bossi P. Sinonasal cancers treatments: state of the art. Curr Opin Oncol. 2021 May 1;33(3):196-205. doi: 10.1097/CCO.0000000000000726.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2017
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: December 15, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (Estimated): December 20, 2016

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: cisplatin; salivary glands; sinus carcinoma; radiochemotherapy concomitant; protontherapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Musculoskeletal Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Bone Diseases; Nose Diseases; Skull Neoplasms; Bone Neoplasms; Nose Neoplasms; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: GORTEC 2016-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No