Clinical Trials /

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

NCT04116047

Description:

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

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
  • Tongue Squamous Cell Carcinoma
  • Tonsillar Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: CompARE: Escalating Treatment of Intermediate and High-risk Oropharyngeal Cancer (OPC)
  • Official Title: Phase III Randomised Controlled Trial Comparing Alternative Regimens for Escalating Treatment of Intermediate and High-risk Oropharyngeal Cancer

Clinical Trial IDs

  • ORG STUDY ID: RG 14-093
  • SECONDARY ID: 2014-003389-26
  • SECONDARY ID: ISRCTN41478539
  • NCT ID: NCT04116047

Conditions

  • Oropharyngeal Cancer

Interventions

DrugSynonymsArms
CisplatinCDDP, PlatinolArm 1 (control): chemoradiotherapy
DurvalumabMEDI-4736, ImfinziArm 5: Durvalumab + Arm 1

Purpose

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

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1 (control): chemoradiotherapyActive ComparatorConcomitant chemoradiotherapy, 3-weekly cisplatin 100mg/m2 or weekly 40mg/m2 with Intensity Modulated Radiotherapy (IMRT) using 70 gray (Gy) in 35F(fractions) +/- neck dissection as indicated by clinical and radiological assessment 3-months post treatment. This is the international gold standard.
  • Cisplatin
Arm 3: Dose-escalated chemoradiotherapyExperimentalDose-escalated chemoradiotherapy using intensity modulated radiotherapy (IMRT) 64Gy in 25F + Cisplatin 100mg/m2 day 1 of week 1 and of week 5 or weekly 40mg/m2. Neck dissection as indicated by clinical and radiological assessment at 3-months post-treatment.
  • Cisplatin
Arm 5: Durvalumab + Arm 1ExperimentalOne dose of induction durvalumab 1500mg by intravenous (IV) infusion followed by arm 1 within four weeks. Within one-two weeks after the completion of arm 1, durvalumab 1500mg every four weeks will be initiated for a total of 6 months
  • Cisplatin
  • Durvalumab

Eligibility 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
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Patient Overall survival (OS)
Time Frame:from randomisation until date of death from any cause (follow-up until 8 years post-treatment)
Safety Issue:
Description:defined as the interval in whole days between date of randomisation and date of death from any cause

Secondary Outcome Measures

Measure:Number of Acute (<3 months post-treatment) toxicity events experienced
Time Frame:From date of randomisation until 2 year follow-up
Safety Issue:
Description: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).
Measure:Number of late (up to 2 years post-treatment) toxicity events experienced using CTCAE
Time Frame:From date of randomisation until 2 year follow-up
Safety Issue:
Description: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.
Measure:Number of late (up to 2 years post-treatment) toxicity events experienced using RTOG
Time Frame:From date of randomisation until 2 year follow-up
Safety Issue:
Description: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
Measure:Head and neck specific quality of life at 2 years post-randomisation using EORTC C30
Time Frame:From date of randomisation until 2 year follow-up
Safety Issue:
Description: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
Measure:Head and neck specific Quality of Life at 2 years post-randomisation
Time Frame:From date of randomisation until 2 year follow-up
Safety Issue:
Description: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
Measure:Swallowing outcomes assessed using MDADI Questionnaire at 24 months post-chemoradiotherapy
Time Frame:From date of randomisation until 2 year follow-up
Safety Issue:
Description: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
Measure:Levels of Percutaneous Endoscopic Gastrostomy (PEG) use
Time Frame:From date of randomisation until 2 year follow-up
Safety Issue:
Description:PEG use will be assessed at baseline, throughout treatment and during 2 year follow-up period
Measure:Cost effectiveness of treatment as assessed using EuroQol Group (EQ-5D) questionnaire
Time Frame:From date of randomisation until 2 year follow-up
Safety Issue:
Description: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
Measure:Surgical complication rates in each arm for patients who require a neck dissection at 4 months following the 3 month post-chemoradiotherapy assessment scan.
Time Frame:At 4 months following the 3 month post-chemoradiotherapy scan
Safety Issue:
Description:Surgical complication rates will be assessed at trial visits if a neck dissection is required at 4 months post-chemotherapy

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Birmingham

Trial Keywords

  • Oropharyngeal cancer
  • HPV

Last Updated

March 27, 2020