Cisplatin + Radiotherapy vs Durvalumab + Radiotherapy Followed by Durvalumab vs Durvalumab + Radiotherapy Followed by Tremelimumab + Durvalumab in Intermediate-Risk HPV-Positive Oropharyngeal SCC

NCT03410615 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: HN9
• Study Type: interventional
• Target: 129
• Locations: 4 countries
• Sites: 26

Brief Summary

Sometimes, cancer patients receive an initial treatment, followed by additional treatment to lower the chance of cancer coming back. The standard or usual treatment for this type of disease is initially having radiation therapy at the same time as chemotherapy (with a drug called cisplatin), with no additional therapy afterwards

Conditions

Oropharyngeal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 3 year event-free survival

  Event-free survival (EFS), is defined as the time from randomization to the time when a failure event is observed. Failure is define by Local-regional progression or recurrence, Distant metastasis, Non-protocol RT, chemotherapy, Surgery or death.

  3 years

Secondary Outcomes (13)

• Functional Assessment of Cancer Therapy-Head and Neck Version (FACT-HN) score.

  6 years

• Local regional failure

  6 years

• Distant metastasis-free survival

  6 years

• Overall survival

  6 years

• Cost-effectiveness of immunotherapy-based treatment arm vs standard of RT and cisplatin in patients with intermediate risk LA-OSC using the EQ-5D-5L

  6 years

Study Arms (3)

Radiation/Cisplatin

ACTIVE COMPARATOR

All patients will receive standard fractionation radiation therapy (RT) scheme: 70 Gy in 35 fractions over 7 weeks (i.e. 2 Gy per fraction) Cisplatin IV 100 mg/m2 days 1, 22, 43 concurrently with RT

Radiation: Radiation; Drug: Cisplatin

Radiation/Durvalumab + Adjuvant Durvalumab

EXPERIMENTAL

All patients will receive standard fractionation radiation therapy (RT) scheme: 70 Gy in 35 fractions over 7 weeks (i.e. 2 Gy per fraction) Concurrent Phase: Durvalumab IV 1500 mg, days -7 and 22 (the second dose is given concurrently with RT). Adjuvant Phase (to start 4 weeks after completion of concurrent phase): Durvalumab IV 1500 mg q4 weekly for 6 doses.

Radiation: Radiation; Drug: Durvalumab

Radiation/Durvalumab + Adjuvant Durvalumab/Tremelimumab

EXPERIMENTAL

ARM CLOSED TO ACCRUAL WITH AMENDMENT #1

Radiation: Radiation; Drug: Durvalumab; Drug: Tremelimumab

Interventions

Radiation RADIATION

70 Gy in 35 fractions over 7 weeks (i.e. 2 Gy per fraction)

Radiation/Cisplatin; Radiation/Durvalumab + Adjuvant Durvalumab; Radiation/Durvalumab + Adjuvant Durvalumab/Tremelimumab

Cisplatin DRUG

100 mg/m2 days 1, 22, 43 concurrently with RT

Radiation/Cisplatin

Tremelimumab DRUG

ARM CLOSED TO ACCRUAL - 2019

Radiation/Durvalumab + Adjuvant Durvalumab/Tremelimumab

Durvalumab DRUG

Given in concurrent and adjuvant phase

Radiation/Durvalumab + Adjuvant Durvalumab; Radiation/Durvalumab + Adjuvant Durvalumab/Tremelimumab

Eligibility Criteria

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

You may qualify if:

• Histologically and/or cytologically confirmed (primary lesion or regional lymph nodes) squamous cell carcinoma of the oropharynx (OSCC) which is locoregionally advanced, intermediate risk and non-metastatic (M0) as defined by the following (UICC/AJCC 8th Edition staging)
• T1-2 N1 (smoking ≥ 10 pack years);
• T3 N0-N1 (smoking ≥ 10 pack years);
• T1-3 N2 (any smoking hx).
• Human papillomavirus (HPV)-related as determined by positive p16 immunohistochemical staining on any tumour specimens. Positive p16 expression is defined as strong and diffuse nuclear and cytoplasmic staining in 70% or more of the tumour cells. Local testing is acceptable; testing will not be done centrally in real-time.
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix I) and a body weight of \> 30 kg.
• The following radiological investigations must be done within 8 weeks of randomization:
• CT or MRI of the neck (with PET-CT and head imaging as indicated);
• CT chest or x-ray, other radiology tests as clinically indicated.
• Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.
• Patient must consent to provision of, and investigator(s) must confirm location and commit to obtain a representation of formalin fixed paraffin block, of non-cytology tissue samples in order that the specific correlative mark assays may be conducted.
• Patient must consent to provision of samples of blood, saliva and oropharyngeal swab in order that the specific correlative marker assays may be conducted
• Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life and health economics questionnaires in the languages provided.
• Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre
• In accordance with CCTG policy, protocol treatment (cisplatin/RT or durvalumab) is to begin within 1 week of randomization.

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
• Current history of other non-OSCC malignancies of the head and neck.
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab, or an anti-CTLA4, including tremelimumab.
• Any previous cisplatin or carboplatin chemotherapy.
• Any previous induction chemotherapy for current SCCHN.
• Any previous surgical treatment of the current cancer (except for a diagnostic biopsy) and no major surgery within 28 days prior to randomization.
• Any previous radiation to the head and neck region that would result in overlap of fields for the current study.
• History of allergic or hypersensitivity reactions to any study drug or their excipients.
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome.
• History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization\* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction
• Current or prior use of immunosuppressive medication within 28 days of study entry, with the exceptions of intranasal and inhaled corticosteroids or systemic chronic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Corticosteroids used on study for anti-emetic purpose are allowed. Corticosteroids as premedication for hypersensitivity reactions (e.g. computed tomography \[CT\] scan premedication) are allowed.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease (controlled by diet alone) or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
• Patients with vitiligo or alopecia;
• Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years);
• Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement;

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator

Study Sites (26)

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

University Hospital of Antwerp

Edegem, Belgium

Location

University Hospital of Gent

Ghent, 9000, Belgium

Location

University Hospital Leuven

Leuven, B-3000, Belgium

Location

Clinique St. Elizabeth

Namur, 5000, Belgium

Location

AZ Sint Augustinus

Wilrijk, B-2610, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

The Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

The Research Institute of the McGill University

Montreal, Quebec, H4A 3J1, Canada

Location

CIUSSS de l'Estrie - Centre hospitalier

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

University Hospital Vall dHebron

Barcelona, 08035, Spain

Location

Hospital Duran i Reynals

Barcelona, 08907, Spain

Location

University Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

University Clinical Hospital of Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiation; Cisplatin; durvalumab; tremelimumab

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)

Physical Phenomena; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Anna Spreafico

  UNH/Princess Margaret Cancer Centre, Toronto ON Canada

  STUDY CHAIR

• Khalil Sultanem

  The Jewish General Hospital, Montreal QC, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: This is a non-comparative, randomized, phase II study of cisplatin plus radiotherapy or durvalumab plus radiotherapy followed by adjuvant durvalumab or durvalumab plus radiotherapy followed by adjuvant tremelimumab and durvalumab in intermediate risk, HPV-positive, locoregionally advanced oropharyngeal squamous cell cancer (LA-OSCC) of the head and neck.

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 25, 2018
• Study Start: May 28, 2018
• Primary Completion: January 9, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (14); ES (5); IT (1); BE (6)