Phase III randomised controlled trial Comparing Alternative Regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer (CompARE)

Phase 1

• Conditions: Oropharyngeal Cancer; MedDRA version: 20.0Level: PTClassification code 10031096Term: Oropharyngeal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-003389-26-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-07-24
• Last Update Posted: 19 October 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Inclusion Criteria:

1.Oropharyngeal squamous cell carcinoma (OPSCC) in base of tongue and tonsil (includes bilateral tumours) and uvula, with a Multidisciplinary Team (MDT) recommendation for treatment with definitive concurrent chemoradiotherapy

2.All OPC T4 or N3 (HPV-pos and HPV-neg)
OR
all HPV-neg OPC T1-T4, N1-N3 or T3-4, N0
OR
HPV-pos OPC T1-T4 with N2b-N3 nodes AND who are smokers = 10 pack years current or previous smoking history

3.Minimum life expectancy of 3 months

4.Eastern Cooperative Oncology Group (ECOG) performance status 0-1

5.Body weight of >30kg

6.Adequate renal function, estimated glomerular filtration rate (eGFR) >50ml/min calculated using Cockcroft-Gault formula

7.Adequate bone marrow function (absolute neutrophil count (ANC) =1.5 x 109/L, haemoglobin =9.0g/dL and platelets =100 x 109/L)

8.Adequate liver function i.e. serum bilirubin =1.5 times the upper limit of normal (ULN), AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal

9.Prothrombin time (PT) =1.5 x ULN or International Normalised Ratio (INR) =1. 5

10.No cancers in previous 5 years, except basal cell carcinoma of skin and cervical intra-epithelial neoplasia (CIN)

11. Aged 18-70

12. Written informed consent given for the trial

13.Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

-Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

-Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >12 months ago, had chemotherapy-induced menopause with last menses >12 months ago ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

14. Willingness to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations including follow up

Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 380
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 265

Exclusion Criteria

Exclusion Criteria

1.All T1-T2,N0 OPC (HPV-pos or HPV-neg)

2.HPV positive patients who are:
•T1-T3, N0-N2c non-smokers
•T1-T3, N0-N2c smokers with =10 pack years or
T1-T2, N0-N2a smokers with =10 pack years

3.Unfit for chemoradiotherapy regimens

4.Creatinine Clearance <50ml/min

5.Treatment with any of the following, prior to randomisation:
a.Any Investigational Medicinal Products (IMP) within 30 days
b.Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks
c.Major surgical procedure (as defined by the Investigator) within 4 weeks, unless for diagnostic purposes.
d. Concurrent use of hormonal therapy for non-cancer-
related conditions (e.g., hormone replacement therapy
is acceptable)
6.History of allergic reactions or hypersensitivity to any of the IMPs and excipients used in this trial

7.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhoea or any subject known to have psychiatric illness/social situations that would limit compliance with study requirement, substantially increase the risk of incurring AEs or compromise the ability of the subject to give written informed consent

8.Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA

9. Women who are pregnant or breast-feeding. Women of child-
bearing potential must have a negative pregnancy test performed within 7 days prior to randomisation

10.Men or women who are not prepared to practise methods of contraception of proven efficacy during treatment and for 6 months following the end of treatment

11.Any condition that, in the opinion of the Investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Additional Exclusion Criteria for Arm 5 only:
Note: from 12-Sep-2019 all patients who enter the trial must be eligible for Arm 5

12.Any previous treatment with PD-L or PD-L1 inhibitor, including durvalumab

13.Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, The following are exceptions to this criterion:
•Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection)
•Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
•Steroids as premedication for hypersensitivity reactions (e.g., CT scan, premedication)

14.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), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polya

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified