Clinical Trials /

Cisplatin Plus Radiotherapy vs Durvalumab Plus Radiotherapy Followed by Durvalumab vs Durvalumab Plus Radiotherapy Followed by Tremelimumab and Durvalumab in Intermediate Risk HPV-Positive Oropharyngeal SCC

NCT03410615

Description:

Sometimes, cancer patients receive an initial treatment, followed by additional treatment to lower the chance of cancer coming back. The standard or usual treatment for this type of disease is initially having radiation therapy at the same time as chemotherapy (with a drug called cisplatin), with no additional therapy afterwards

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Cisplatin Plus Radiotherapy vs Durvalumab Plus Radiotherapy Followed by Durvalumab vs Durvalumab Plus Radiotherapy Followed by Tremelimumab and Durvalumab in Intermediate Risk HPV-Positive Oropharyngeal SCC
  • Official Title: Randomized Phase II Study of Cisplatin Plus Radiotherapy Versus Durvalumab Plus Radiotherapy Followed by Adjuvant Durvalumab Versus Durvalumab Plus Radiotherapy Followed by Adjuvant Tremelimumab and Durvalumab in Intermediate Risk HPV-Positive Locoregionally Advanced Oropharyngeal Squamous Cell Cancer (LA-OSCC)

Clinical Trial IDs

  • ORG STUDY ID: HN9
  • NCT ID: NCT03410615

Conditions

  • Oropharyngeal Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
CisplatinRadiation/Cisplatin
DurvalumabRadiation/Durvalumab + Adjuvant Durvalumab
TremelimumabRadiation/Durvalumab + Adjuvant Durvalumab/Tremelimumab

Purpose

Sometimes, cancer patients receive an initial treatment, followed by additional treatment to lower the chance of cancer coming back. The standard or usual treatment for this type of disease is initially having radiation therapy at the same time as chemotherapy (with a drug called cisplatin), with no additional therapy afterwards

Detailed Description

      This study is looking at whether a type of drug called durvalumab can be used with radiation
      during the initial treatment, (instead of cisplatin) and also afterwards as additional
      therapy. Durvalumab is an immunotherapy drug . It has been tested in many different types of
      cancers. Durvalumab works by allowing the immune system to detect the cancer and reactivate
      the immune response. This may help to slow down the growth of cancer or may cause cancer
      cells to die. Durvalumab has been shown to shrink tumours in animals. It has been studied in
      more than 5000 people, approved for use in other cancers and seems promising.

      This clinical trial will also test another type of immunotherapy drug called tremelimumab,
      which would also be given as additional treatment. Tremelimumab works in a different way to
      durvalumab to enhance the immune system reaction against cancer cells and may improve the
      effect of durvalumab. Tremelimumab may also help slow the growth of the cancer cells or may
      cause cancer cells to die. It has been shown to shrink tumours in animals. Tremelimumab has
      been studied in over 1200 people, approved for use in other cancers and seems promising.
    

Trial Arms

NameTypeDescriptionInterventions
Radiation/CisplatinActive ComparatorAll patients will receive standard fractionation radiation therapy (RT) scheme: 70 Gy in 35 fractions over 7 weeks (i.e. 2 Gy per fraction) Cisplatin IV 100 mg/m2 days 1, 22, 43 concurrently with RT
  • Cisplatin
Radiation/Durvalumab + Adjuvant DurvalumabExperimentalAll patients will receive standard fractionation radiation therapy (RT) scheme: 70 Gy in 35 fractions over 7 weeks (i.e. 2 Gy per fraction) Concurrent Phase: Durvalumab IV 1500 mg, days -7 and 22 (the second dose is given concurrently with RT). Adjuvant Phase (to start 4 weeks after completion of concurrent phase): Durvalumab IV 1500 mg q4 weekly for 6 doses.
  • Durvalumab
Radiation/Durvalumab + Adjuvant Durvalumab/TremelimumabExperimentalAll patients will receive standard fractionation radiation therapy (RT) scheme: 70 Gy in 35 fractions over 7 weeks (i.e. 2 Gy per fraction) Concurrent Phase: Durvalumab IV 1500 mg, days -7 and 22 (the second dose is given concurrently with RT). Adjuvant Phase (to start 4 weeks after completion of concurrent phase): Tremelimumab IV 75 mg q4 weekly for 4 doses + Durvalumab IV 1500 mg q4 weekly for 6 doses
  • Durvalumab
  • Tremelimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically and/or cytologically confirmed (primary lesion or regional lymph nodes)
             squamous cell carcinoma of the oropharynx (OSCC) which is locoregionally advanced,
             intermediate risk and non-metastatic (M0) as defined by the following (UICC/AJCC 8th
             Edition staging)

               -  T1-2 N1 (smokers);

               -  T3 N0-N1 (smokers);

               -  T1-3 N2 (any smoking hx).

          -  Human papillomavirus (HPV)-related as determined by positive p16 immunohistochemical
             staining on any tumour specimens. Positive p16 expression is defined as strong and
             diffuse nuclear and cytoplasmic staining in 70% or more of the tumour cells. Local
             testing is acceptable; testing will not be done centrally in real-time.

          -  Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
             (see Appendix I) and a body weight of > 30 kg.

          -  The following radiological investigations must be done within 8 weeks of
             randomization:

               -  CT or MRI of the head and neck (with PET-CT as indicated);

               -  CT chest or x-ray, other radiology tests as clinically indicated.

          -  Women/men of childbearing potential must have agreed to use a highly effective
             contraceptive method.

          -  Patient must consent to provision of, and investigator(s) must confirm adequacy, of
             non-cytology tissue samples and confirm access to and agree to submit within 4 weeks
             of randomization to the CCTG Central Tumour Bank, a representative formalin fixed
             paraffin block of non-cytology tumour tissue in order that the specific correlative
             mark assays may be conducted.

          -  Patient must consent to provision of samples of blood, saliva and oropharyngeal swab
             in order that the specific correlative marker assays may be conducted

          -  Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life
             and health economics questionnaires in the languages provided.

          -  Patients must be accessible for treatment and follow-up. Patients registered on this
             trial must be treated and followed at the participating centre

          -  In accordance with CCTG policy, protocol treatment (cisplatin/RT or durvalumab) is to
             begin within 1 week of randomization.

          -  The patient is not receiving anti-cancer therapy in a concurrent clinical study
             testing new treatments or treatment strategies and the patient agrees not to
             participate in other clinical studies during their participation in this trial while
             on study treatment.

          -  Adequate normal organ and marrow function as defined below (must be done within 14
             days prior to randomization): Absolute neutrophils - ≥ 1.5 x 10^9/L; Platelets ≥100 x
             10^9; Hemoglobin ≥90 g/L; Bilirubin ≤ 1.5 x UNL; AST and ALT ≤2.5 x UNL; Creatine
             clearance ≥ 60 mL/min.

          -  Patient consent must be appropriately obtained in accordance with applicable local and
             regulatory requirements

          -  Patients must be assessed by a radiation oncologist and medical oncologist and deemed
             suitable for study participation

        Exclusion Criteria:

          -  Patients with a history of other malignancies, except: adequately treated non-melanoma
             skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
             curatively treated with no evidence of disease for ≥ 5 years.

          -  Current history of other non-OSCC malignancies of the head and neck.

          -  Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab, or an
             anti-CTLA4, including tremelimumab.

          -  Any previous cisplatin or carboplatin chemotherapy.

          -  Any previous induction chemotherapy for current SCCHN.

          -  Any previous surgical treatment of the current cancer (except for a diagnostic biopsy)
             and no major surgery within 28 days prior to randomization.

          -  Any previous radiation to the head and neck region that would result in overlap of
             fields for the current study.

          -  Peripheral neuropathy ≥ grade 2 (CTCAE v4.0).

          -  Hearing loss/tinnitus ≥ grade 3 (CTCAE v4.0).

          -  History of allergic or hypersensitivity reactions to any study drug or their
             excipients.

          -  Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec
             in screening ECG measured using standard institutional method or history of familial
             long QT syndrome.

          -  History of primary immunodeficiency, history of allogenic organ transplant that
             requires therapeutic immunosuppression and the use of immunosuppressive agents within
             28 days of randomization* or a prior history of severe (grade 3 or 4) immune mediated
             toxicity from other immune therapy or grade ≥ 3 infusion reaction

          -  Current or prior use of immunosuppressive medication within 28 days of study entry,
             with the exceptions of intranasal and inhaled corticosteroids or systemic chronic
             corticosteroids at physiological doses, which are not to exceed 10 mg/day of
             prednisone, or an equivalent corticosteroid. Corticosteroids used on study for
             anti-emetic purpose are allowed. Corticosteroids as premedication for hypersensitivity
             reactions (e.g. computed tomography [CT] scan premedication) are allowed.

          -  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 (controlled by diet alone) or other
             serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus
             erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with
             polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3
             years prior to the start of treatment. The following are exceptions to this criterion:

          -  Patients with vitiligo or alopecia;

          -  Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment
             (within the last 2 years);

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

          -  Any chronic skin condition that does not require systemic therapy.

          -  Patients with active or uncontrolled intercurrent illness including, but not limited
             to:

               -  cardiac dysfunction (symptomatic congestive heart failure, uncontrolled
                  hypertension, unstable angina pectoris, cardiac arrhythmia);

               -  active peptic ulcer disease or gastritis;

               -  active bleeding diatheses;

               -  psychiatric illness/social situations that would limit compliance with study
                  requirements or compromise the ability of the subject to give written informed
                  consent;

               -  known history of previous clinical diagnosis of tuberculosis;

               -  known human immunodeficiency virus infection (positive HIV 1/2 antibodies);

               -  known active hepatitis B infection (positive HBV surface antigen (HBsAg).
                  Patients with a past or resolved HBV infection (defined as presence of hepatitis
                  B core antibody (anti-HBc) and absence of HBsAg) are eligible;

               -  known active hepatitis C infection. Patients positive for hepatitis C (HCV)
                  antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

          -  History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or
             evidence of interstitial lung disease on baseline CT scan.

          -  Receipt of live attenuated vaccination (examples include, but are not limited to,
             vaccines for measles, mumps, and rubella, live attenuated influenza vaccine (nasal),
             chicken pox vaccine, oral polio vaccine, rotavirus vaccine, yellow fever vaccine, BCG
             vaccine, typhoid vaccine and typhus vaccine) within 30 days prior to randomization.

          -  Pregnant or lactating women

          -  Any active disease condition which would render the protocol treatment dangerous or
             impair the ability of the patient to receive protocol therapy.

          -  Any condition (e.g. psychological, geographical, etc.) that does not permit compliance
             with the protocol
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:3 year event-free survival
Time Frame:3 years
Safety Issue:
Description:Event-free survival (EFS), is defined as the time from randomization to the time when a failure event is observed. Failure is define by Local-regional progression or recurrence, Distant metastasis, Non-protocol RT, chemotherapy, Surgery or death.

Secondary Outcome Measures

Measure:Functional Assessment of Cancer Therapy-Head and Neck Version (FACT-HN) score.
Time Frame:3 years
Safety Issue:
Description:The FACT-H&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients (1-3). It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for head and neck related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as an global QoL score. Higher scores represent better QoL.
Measure:Local regional failure
Time Frame:3 years
Safety Issue:
Description:Locoregional control defined as time from randomization to the time of first documented local (primary site) or regional (lymph node) recurrence
Measure:Distant metastasis-free survival
Time Frame:3 years
Safety Issue:
Description:Distant metastasis-free survival defined as time from randomization to the time of first documented distant metastasis or death from any cause
Measure:Overall survival
Time Frame:3 years
Safety Issue:
Description:Overall Survival defined as time from randomization to the time of death from any cause

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Canadian Cancer Trials Group

Last Updated

April 17, 2018