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

  • STATUS
    Recruiting
  • End date
    Jul 31, 2026
  • participants needed
    180
  • sponsor
    Canadian Cancer Trials Group
Updated on 19 September 2021
Investigator
Wendy Parulekar
Primary Contact
QEII Health Sciences Centre (0.8 mi away) Contact
+29 other location
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 IdentifierNCT03410615
SponsorCanadian Cancer Trials Group
Last Modified on19 September 2021

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 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
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
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
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

Exclusion Criteria

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
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
History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline CT scan
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
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