Overview

CompARE: Escalating Treatment of Intermediate and High-risk Oropharyngeal Cancer (OPC)

Status:
Recruiting
Trial end date:
2023-01-01
Target enrollment:
0
Participant gender:
All
Summary
CompARE is a multicentre, phase III open-label randomised controlled trial using an adaptive, Multi-Arm, Multi-Stage (MAMS) design.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Birmingham
Collaborator:
AstraZeneca
Treatments:
Cisplatin
Durvalumab
Criteria
Inclusion Criteria:

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

2. All OPC T4 or N3 (HPV+ and HPV-) OR all HPV -ve (negative) OPC T1-T4, N1-N3 or T3-4,
N0 OR HPV +ve (positive) 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. Adequate renal function, glomerular filtration rate (GFR) >50ml/min calculated using
Cockcroft-Gault formula

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

7. Adequate liver function i.e. plasma bilirubin ≤1.5 times the upper limit of normal
(ULN), and alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤2.5 x ULN

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

9. Magnesium ≥ lower limit of normal

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. Surgically resectable disease if being randomised to all four arms

14. Females must either be of non-reproductive potential (i.e. post-menopausal by history:
≥55 years old and no menses for ≥1 year without an alternative medical cause; or
history of hysterectomy, or history of bilateral tubal ligation or history of
bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry

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

Exclusion Criteria:

1. All T1-T2,N0 OPC (HPV +ve or HPV-ve)

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:

1. Any Investigational Medicinal Products (IMP) within 30 days

2. Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks

3. Major surgery within 4 weeks

6. History of allergic reactions 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, active peptic ulcer disease or gastritis, active
bleeding diatheses including any subject known to have evidence of acute or chronic
hepatitis B, hepatitis C, Human Immunodeficiency Virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the subject to give written informed consent

8. 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

9. 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

10. 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:

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

12. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid dose

13. 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, systemic lupus erythematosus, Sarcoidosis syndrome,
or Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis). The following are exceptions to this criterion:

- Patients with vitiligo or alopecia

- Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on
hormone replacement

- Any chronic skin condition that does not require systemic therapy

- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician

14. Patients with an active non-infectious pneumonitis

15. History of primary immunodeficiency

16. History of allogeneic organ transplant

17. Known history of previous clinical diagnosis of tuberculosis

18. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab. Inactivated viruses, such as those in the influenza
vaccine, are permitted