SBRT + Immunomodulating Systemic Therapy for Inoperable, Recurrent H&N

NCT03402737 | Terminated

• 2 other identifiers: EC/2017/06362017-000133-31
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

To derive the maximum tolerated dose of hypofractionated stereotactic body radiotherapy (SBRT) using dose painting by numbers with immunomodulating systemic therapy in patients that are reirradiated for recurrent squamous cell carcinoma of the head and neck.

Conditions

Head and Neck Neoplasm

Keywords

Stereotactic body radiotherapy; Immunomodulating systemic therapy

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose

  maximum tolerated dose of hypofractionated stereotactic body radiotherapy (SBRT) using dose painting by numbers with immunomodulating systemic therapy in patients that are reirradiated for recurrent squamous cell carcinoma of the head and neck

  3 months after radiotherapy

Secondary Outcomes (11)

• symptom palliation - pain

  through study completion, an average of 12 months

• symptom palliation - dysphagia

  through study completion, an average of 12 months

• local control

  3 months after SBRT and thereafter through study completion, an average of 12 months

• Overall survival

  through study completion, an average of 12 months

• Progression free survival

  through study completion, an average of 12 months

Study Arms (1)

Stereotactic body radiotherapy + IM

EXPERIMENTAL

Single arm phase I trial with 3 Stereotactic Body Radiation Therapy dose-escalation arms.

Radiation: Stereotactic body radiotherapy

Interventions

Stereotactic body radiotherapy RADIATION

The range of dose-painting will be escalated in following levels: * 2x 6-8Gy (day 1-4) * 3x 6-8Gy (day 1-4-7) * 3x 6-10Gy (day 1-4-7) * 3x 6-12Gy (day 1-4-7) Patients will take cyclophosphamide orally 50 mg tablets, 1 tablet a day from the first day of irradiation for 8 consecutive weeks. Nivolumab will be considered as standard therapy in patients with cisplatin refractory locoregional disease recurrence. Nivolumab will be administered as per current standard of care. In case patients that are treated with nivolumab will be included in the trial, they will not be treated with cyclophosphamide.

Stereotactic body radiotherapy + IM

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed local, regional or combined locoregional recurrence of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx or cancer of unknown primary (CUP) in the neck in previously irradiated tissue, with former irradiation with curative intent.
• Patients with non-symptomatic distant metastases and local, regional or combined locoregional recurrence can be included.
• In case of non-metastatic disease, the recurrence must be primarily unresectable recurrence and/or patients refused surgery.
• Time interval 6-24 months after the end of the initial radio(chemo)therapy for primary head and neck cancer.
• Decision of the Head and Neck Tumor Boards at the recruiting centre to offer salvage radio(chemo)therapy, palliative chemotherapy or anti-PD-1 antibody treatment with nivolumab for cisplatin-refractory locoregional recurrent head and neck squamous cell carcinoma.
• Karnofsky performance status ≥ 70.
• Age ≥ 18 years old.
• Informed consent obtained, signed and dated before specific protocol procedures.

You may not qualify if:

• Previous radiotherapy was for cT1-2 cN0 M0 glottic cancer.
• Grade ≥ 4 late toxicity after the initial radio(chemo)therapy.
• Brachytherapy as treatment for second primary / recurrence.
• Previous (combination with) immunotherapy for the primary or the recurrent squamous cell carcinoma.
• Impossibility of oral intake of cyclophosphamide.
• For patients receiving cyclophosphamide: necessary intake during therapy of allopurinol, amiodarone, digoxin, hydrochlorothiazide, indomethacin, phenobarbital, phenytoin, warfarin. clopidogrel, ticlopidine, carbamazepine, efavirenz, rifampicin, ritonavir
• High risk for arterial blow-out: 1 of following criteria is sufficient to exclude patients:
• soft tissue necrosis
• skin invasion of the recurrent cancer
• circumferential involvement of \> 180° of a carotid artery
• Symptomatic distant metastases.
• Other uncontrolled second primary tumors.
• Pregnant or lactating women.
• Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study.
• Patient unlikely to comply with protocol, i.e. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study.

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (3)

Radiotherapy department, University Hospital Ghent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

CHU Namur

Namur, Belgium

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Fréderic Duprez, MD, PhD

  Gent University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The range of dose-painting will be escalated in following levels: * 2x 6-8Gy * 3x 6-8Gy The standard "3+3" design will be used for the this trial. To obtain more precise toxicity rate of the MTD we will double the number of patients at the first dose prescription that gives totally 6 patients. The 3 remaining dose levels will include 3 patients each. Thus, fifteen (6+3+3+3) patients will be included in this radiotherapy dose finding study investigating the MTD. The number of patients will be doubled in case of 2 DLTs at the dose prescription I and 1 DLT at dose prescriptions II-IV with DLT in a maximum of 10 out of 30 patients. * 3x 6-10Gy * 3x 6-12Gy

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: January 18, 2018
• Study Start: July 31, 2017
• Primary Completion: December 3, 2020
• Study Completion: December 3, 2020
• Last Updated: February 18, 2021

Record last verified: 2021-02

Locations

BE (3)