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

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ClinicalTrials.gov Identifier: NCT04116047
Recruitment Status : Recruiting
First Posted : October 4, 2019
Last Update Posted : March 30, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University of Birmingham

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

Condition or disease Intervention/treatment Phase
Oropharyngeal Cancer Drug: Cisplatin Drug: Durvalumab Procedure: Radiotherapy Procedure: Dose-escalated radiotherapy Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 695 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III Randomised Controlled Trial Comparing Alternative Regimens for Escalating Treatment of Intermediate and High-risk Oropharyngeal Cancer
Actual Study Start Date : July 2015
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Active Comparator: Arm 1 (control): chemoradiotherapy
Concomitant 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.
Drug: Cisplatin
Other Name: CDDP, Platinol

Procedure: Radiotherapy
Experimental: Arm 3: Dose-escalated chemoradiotherapy
Dose-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.
Drug: Cisplatin
Other Name: CDDP, Platinol

Procedure: Dose-escalated radiotherapy
Experimental: Arm 5: Durvalumab + Arm 1
One 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
Drug: Cisplatin
Other Name: CDDP, Platinol

Drug: Durvalumab
Other Name: MEDI-4736, Imfinzi

Procedure: Radiotherapy



Primary Outcome Measures :
  1. Patient Overall survival (OS) [ Time Frame: from randomisation until date of death from any cause (follow-up until 8 years post-treatment) ]
    defined as the interval in whole days between date of randomisation and date of death from any cause

  2. Patient Event Free Survival (EFS) [ Time Frame: From randomisation until date of progression/persistence/recurrence/death (follow-up until 8 years post-treatment) ]
    defined as the interval in whole days between date of randomisation until date of progression/persistence/recurrence/death


Secondary Outcome Measures :
  1. Number of Acute (<3 months post-treatment) toxicity events experienced [ Time Frame: From date of randomisation until 2 year follow-up ]
    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).

  2. 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 ]
    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.

  3. 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 ]
    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

  4. 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 ]
    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

  5. Head and neck specific Quality of Life at 2 years post-randomisation [ Time Frame: From date of randomisation until 2 year follow-up ]
    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

  6. Swallowing outcomes assessed using MDADI Questionnaire at 24 months post-chemoradiotherapy [ Time Frame: From date of randomisation until 2 year follow-up ]
    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

  7. Levels of Percutaneous Endoscopic Gastrostomy (PEG) use [ Time Frame: From date of randomisation until 2 year follow-up ]
    PEG use will be assessed at baseline, throughout treatment and during 2 year follow-up period

  8. Cost effectiveness of treatment as assessed using EuroQol Group (EQ-5D) questionnaire [ Time Frame: From date of randomisation until 2 year follow-up ]
    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

  9. 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 ]
    Surgical complication rates will be assessed at trial visits if a neck dissection is required at 4 months post-chemotherapy



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04116047


Contacts
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Contact: Charlotte Firth CompARE@trials.bham.ac.uk
Contact: Isla Humphreys CompARE@trials.bham.ac.uk

Locations
Show Show 33 study locations
Sponsors and Collaborators
University of Birmingham
AstraZeneca
Investigators
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Principal Investigator: Prof Mehanna University of Birmingham
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Responsible Party: University of Birmingham
ClinicalTrials.gov Identifier: NCT04116047    
Other Study ID Numbers: RG 14-093
2014-003389-26 ( EudraCT Number )
ISRCTN41478539 ( Registry Identifier: International Standard Randomised Clinical Trial Number )
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: March 30, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Birmingham:
Oropharyngeal cancer
HPV
Additional relevant MeSH terms:
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Oropharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Durvalumab
Antineoplastic Agents
Antineoplastic Agents, Immunological