Randomized Phase II Study of Cisplatin Plus Radiotherapy Versus Durvalumab Plus Radiotherapy Followed by Adjuvant Durvalumab Versus Durvalumab Plus Radiotherapy Followed by Adjuvant Tremelimumab and Durvalumab in Intermediate Risk HPV-Positive Locoregionally Advanced Oropharyngeal Squamous Cell Cancer (LA-OSCC)

STATUS

Recruiting
End date

Jul 31, 2026
participants needed

180
sponsor

Canadian Cancer Trials Group

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Updated on 25 October 2022

See if I qualify

cancer

carcinoma

x-rays

neutrophil count

durvalumab

human papillomavirus

pet/ct scan

treatment schedule

oropharyngeal carcinoma

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

Description

This study is looking at whether a type of drug called durvalumab can be used with radiation during the initial treatment, (instead of cisplatin) and also afterwards as additional therapy. Durvalumab is an immunotherapy drug . It has been tested in many different types of cancers. Durvalumab works by allowing the immune system to detect the cancer and reactivate the immune response. This may help to slow down the growth of cancer or may cause cancer cells to die. Durvalumab has been shown to shrink tumours in animals. It has been studied in more than 5000 people, approved for use in other cancers and seems promising.

This clinical trial will also test another type of immunotherapy drug called tremelimumab, which would also be given as additional treatment. Tremelimumab works in a different way to durvalumab to enhance the immune system reaction against cancer cells and may improve the effect of durvalumab. Tremelimumab may also help slow the growth of the cancer cells or may cause cancer cells to die. It has been shown to shrink tumours in animals. Tremelimumab has been studied in over 1200 people, approved for use in other cancers and seems promising.

As of February 2019, tremelimumab will no longer be tested with new participants joining the study.

Details

Condition	Oropharyngeal Squamous Cell Carcinoma
Treatment	cisplatin, tremelimumab, Radiation, durvalumab
Clinical Study Identifier	NCT03410615
Sponsor	Canadian Cancer Trials Group
Last Modified on	25 October 2022

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	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
	Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix I) and a body weight of > 30 kg
	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
	The following radiological investigations must be done within 8 weeks of
	randomization
	cells. Local testing is acceptable; testing will not be done centrally in
	CT or MRI of the neck (with PET-CT and head imaging as indicated)
	real-time
	CT chest or x-ray, other radiology tests as clinically indicated
	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
	Women/men of childbearing potential must have agreed to use a highly effective
	contraceptive method
	In accordance with CCTG policy, protocol treatment (cisplatin/RT or durvalumab) is to begin within 1 week of randomization
	The patient is not receiving anti-cancer therapy in a concurrent clinical study testing new treatments or treatment strategies and the patient agrees not to participate in other clinical studies during their participation in this trial while on study treatment
	Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements
	Patients must be assessed by a radiation oncologist and medical oncologist and deemed suitable for study participation including administration of radiotherapy, cisplatin and durvalumab as outlined in the protocol
	Adequate normal organ and marrow function as defined below (must be done within 14 days prior to randomization): Absolute neutrophils - ≥ 1.5 x 10^9/L; Platelets ≥100 x 10^9; Hemoglobin ≥90 g/L; Bilirubin ≤ 1.5 x UNL; AST and ALT ≤2.5 x UNL; Creatine clearance ≥ 60 mL/min
Exclusion Criteria
	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
	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
	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
	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
	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
	Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years)
	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
	Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement
	Any chronic skin condition that does not require systemic therapy
	Patients with active or uncontrolled intercurrent illness including, but not limited
	to
	cardiac dysfunction (symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia)
	active peptic ulcer disease or gastritis
	active bleeding diatheses
	psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
	known history of previous clinical diagnosis of tuberculosis
	known active human immunodeficiency virus infection (positive HIV 1/2 antibodies); HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
	known active hepatitis B infection (positive HBV surface antigen (HBsAg). Patients with a past or resolved HBV infection (defined as presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible
	known active hepatitis C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
	Receipt of live attenuated vaccination (examples include, but are not limited to, vaccines for measles, mumps, and rubella, live attenuated influenza vaccine (nasal), chicken pox vaccine, oral polio vaccine, rotavirus vaccine, yellow fever vaccine, BCG vaccine, typhoid vaccine and typhus vaccine) within 30 days prior to randomization
	Pregnant or lactating women
	Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy
	Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol
	History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or
	evidence of interstitial lung disease on baseline CT scan

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