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

Oropharyngeal Cancer Clinical Trial

— CompARE  

Official title:

Phase III Randomised Controlled Trial Comparing Alternative Regimens for Escalating Treatment of Intermediate and High-risk Oropharyngeal Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04116047
• Other study ID #: RG 14-093
• Secondary ID: 2014-003389-26IS
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 2015
• Est. completion date: December 2030

Study information

• Verified date: May 2024
• Source: University of Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

CompARE is a multicentre, phase III open-label randomised controlled trial using an adaptive, Multi-Arm, Multi-Stage (MAMS) design.

Description:

The CompARE Trial examines alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer in an adult patient population. The aim is to assess whether escalated radiotherapy, adding surgery or immunotherapy will improve overall survival and quality of life in these patients.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 785
• Est. completion date: December 2030
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Oropharyngeal Cancer
• Oropharyngeal Neoplasms

Intervention

Drug:
• Cisplatin

• Durvalumab

Procedure:
• Radiotherapy

Locations

Country	Name	City	State
Ireland	St James's Hospital	Dublin
Ireland	St Luke's Hospital	Dublin
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Royal United Hospital	Bath
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Queen Elizabeth Hospital	Birmingham	West Midlands
United Kingdom	Bradford Royal Infirmary	Bradford	West Yorkshire
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Cheltenham General Hospital	Cheltenham
United Kingdom	Colchester General Hospital	Colchester	Essex
United Kingdom	Castle Hill Hospital	Cottingham	East Yorkshire
United Kingdom	University Hospital Coventry	Coventry	West Midlands
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Royal Devon and Exeter Hospital	Exeter	Devon
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	St James's University Hospital	Leeds	West Yorkshire
United Kingdom	Leicester Royal Infirmary	Leicester	East Midlands
United Kingdom	Aintree University Hospital	Liverpool
United Kingdom	North Middlesex Hospital	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	James Cook University Hospital	Middlesbrough	North Yorkshire
United Kingdom	Freeman Hospital	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	Norfolk and Norwich University Hospital	Norwich
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Churchill Hospital	Oxford	Oxfordshire
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Royal Preston Hospital	Preston	Lancashire
United Kingdom	Queen's Hospital	Romford	Essex
United Kingdom	Weston Park Hospital	Sheffield	South Yorkshire
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury
United Kingdom	Singleton Hospital	Swansea
United Kingdom	Musgrove Park Hospital	Taunton
United Kingdom	Torbay Hospital	Torquay
United Kingdom	Clatterbridge Cancer Centre	Wirral
United Kingdom	Newcross Hospital	Wolverhampton	West Midlands
United Kingdom	York Hospital	York	North Yorkshire

Sponsors (3)

Lead Sponsor	Collaborator
University of Birmingham	AstraZeneca, Cancer Trials Ireland

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient Overall survival (OS)	defined as the interval in whole days between date of randomisation and date of death from any cause	from randomisation until date of death from any cause (follow-up until 8 years post-treatment)
Primary	Patient Event Free Survival (EFS)	defined as the interval in whole days between date of randomisation until date of progression/persistence/recurrence/death	From randomisation until date of progression/persistence/recurrence/death (follow-up until 8 years post-treatment)
Secondary	Number of Acute (<3 months post-treatment) toxicity events experienced	Total number of acute (<3 months post-treatment) severe (grade 3-5) toxicity events experienced. Adverse events will be collected post-treatment and graded according to Common Terminology Criteria for Adverse Events (CTCAE).	From date of randomisation until 2 year follow-up
Secondary	Number of late (up to 2 years post-treatment) toxicity events experienced using CTCAE	Severe (grade 3-5) adverse events will be collected up to 2 years post randomisation, these events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and version 3.0 for scoring mucositis.	From date of randomisation until 2 year follow-up
Secondary	Number of late (up to 2 years post-treatment) toxicity events experienced using RTOG	Late and severe toxicity events at 2 years post randomisation,will be collected and graded using Radiation Therapy Oncology Group (RTOG) Radiation Morbidity Scoring Criteria	From date of randomisation until 2 year follow-up
Secondary	Head and neck specific quality of life at 2 years post-randomisation using EORTC C30	Patients will complete the European Organisation for Research and Treatment of Cancer (EORTC) C30 questionnaire at baseline, at the end of treatment, and during the follow-up period until 2 years post-treatment	From date of randomisation until 2 year follow-up
Secondary	Head and neck specific Quality of Life at 2 years post-randomisation	Patients will complete the European Organisation for Research and Treatment of Cancer (EORTC) H&N35 questionnaire at baseline, at the end of treatment, and during the follow-up period until 2 years post-treatment	From date of randomisation until 2 year follow-up
Secondary	Swallowing outcomes assessed using MDADI Questionnaire at 24 months post-chemoradiotherapy	Patients will complete the M.D. Anderson Dysphagia Inventory (MDADI) Questionnaire at baseline, at the end of treatment, and during the follow-up period until 2 years post-treatment	From date of randomisation until 2 year follow-up
Secondary	Levels of Percutaneous Endoscopic Gastrostomy (PEG) use	PEG use will be assessed at baseline, throughout treatment and during 2 year follow-up period	From date of randomisation until 2 year follow-up
Secondary	Cost effectiveness of treatment as assessed using EuroQol Group (EQ-5D) questionnaire	Patients will complete the EuroQol Group (EQ-5D) questionnaire at baseline, at the end of treatment, and during the follow-up period until 2 years post-treatment	From date of randomisation until 2 year follow-up
Secondary	Surgical complication rates in each arm for patients who require a neck dissection at 4 months following the 3 month post-chemoradiotherapy assessment scan.	Surgical complication rates will be assessed at trial visits if a neck dissection is required at 4 months post-chemotherapy	At 4 months following the 3 month post-chemoradiotherapy scan