Clinical Trials /

"QUAD SHOT" Radiotherapy With Pembrolizumab in Patients With Recurrent Head & Neck Cancer

NCT04373642

Description:

The purpose of this study is to test the safety of palliative "QUAD SHOT" radiotherapy combined with pembrolizumab and evaluate the effects of the combination treatment patients with recurrent cancer of head and neck.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: "QUAD SHOT" Radiotherapy With Pembrolizumab in Patients With Recurrent Head & Neck Cancer
  • Official Title: A Single-arm Phase II Trial of Palliative "QUAD SHOT" Radiotherapy Combined With Pembrolizumab in Patients With Recurrent Head & Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: OU-SCC-QUADSHOT
  • NCT ID: NCT04373642

Conditions

  • Head and Neck Cancer

Interventions

DrugSynonymsArms
Pebrolizumab + QUADSHOT RadiotherapyPembrolizumab + QUADSHOT Radiotherapy

Purpose

The purpose of this study is to test the safety of palliative "QUAD SHOT" radiotherapy combined with pembrolizumab and evaluate the effects of the combination treatment patients with recurrent cancer of head and neck.

Detailed Description

      During this study, patients will receive infusions of pembrolizumab with radiotherapy
      (palliative QUADSHOT regimen). The patient will receive treatment of pembrolizumab once every
      3 weeks and palliative "QUAD SHOT" radiotherapy every 4 weeks. These 28 day period of time is
      called a cycle. The cycle will be repeated 3 times. Each cycle is numbered in order. The
      patient will be treated for up to 3 cycles followed by pembrolizumab single drug until
      unacceptable toxicity or tumor progression.

      The patient will also complete a survey.

      Total duration of the study is up to two years.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + QUADSHOT RadiotherapyExperimentalCombination Treatment Pembrolizumab by IV once on day 1 of 21 day cycle, begin 7 days before the first round of QUAD SHOT radiotherapy. QUAD SHOT radiotherapy twice a day for two days, begin 7 days after the first dose of pembrolizumab; repeat every 28 days for up to 3 rounds. Maintenance Treatment Pembrolizumab by IV once on day 1 of 21 day cycle On day 21, if the medical oncologist feels that the patient may safely continue treatment, patient will receive a new 21 days cycle of treatment with pebrolizumab.
  • Pebrolizumab + QUADSHOT Radiotherapy

Eligibility Criteria

        Inclusion Criteria:

          1. Age 18 years and older

          2. Written informed consent and any locally-required authorization obtained from the
             patients prior to performing any protocol-related procedures, including screening
             evaluations

          3. Pathologically (histologically or cytologically) proven diagnosis of squamous cell
             carcinoma of the head and neck (nasopharynx, oral cavity, oropharynx, hypopharynx,
             larynx, or unknown primary).

          4. Locally recurrent or metastatic HNSCC not deemed amenable to curative-intent salvage
             therapy, in whom at least six months have passed since their prior RT, if received.

          5. Must have evaluable lesion per RECIST v1.1

          6. Patients agree to provide their smoking history prior to registration

          7. ECOG performance status of 0-2

          8. Adequate bone marrow: absolute neutrophil count ≥ 1,500/μl, platelets ≥ 100,000/μl,
             hemoglobin ≥ 9 g/dL

          9. Adequate hepatic function: total bilirubin ≤ 1.5 X upper normal limit (UNL) (except
             subjects with Gilbert syndrome, who can have total bilirubin < 3 mg/dl), aspartate
             aminotransferase (AST) ≤ 2.5 X UNL, alanine aminotransferase (ALT) ≤ 2.5 X UNL

         10. Adequate renal function: calculated serum creatinine clearance >40 mL/min by the
             Cockcroft-Gault formula or by 24-hour urine collection or Serum creatinine less than
             or equal to 1.5 x upper limit of normal (ULN)

         11. Female patients of reproductive potential and their male partners must agree to
             practice total abstinence or use a highly effective method of contraception (failure
             rate < 1% per year) prior to study entry, during treatment and for 90 days following
             the last dose of study treatment.

         12. Male patient agrees to use an adequate method of contraception

        Exclusion Criteria:

          1. Histologically confirmed other types (Non-SCC) of salivary gland cancer

          2. History of another primary malignancy EXCEPT For:

               1. malignancy treated with curative intent and with no known active disease ≥5 years
                  before the first dose of study drug and of low potential risk for recurrence;

               2. adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease; adequately treated carcinoma in situ without evidence of disease (eg,
                  carcinoma in situ of the breast, oral cavity and cervix are all permissible);

               3. low to favorable intermediate risk prostate cancer based on NCCN criteria on
                  active surveillance, .

          3. Prior radiotherapy to the region of the study cancer within less than 6 months

          4. Patients who have received prior radiation therapy and who, in the opinion of the
             treating radiation oncologist, cannot be reirradiated safely without excess risk of
             severe toxicity given prior radiation dose to critical structures.

          5. Patients with known contraindications to radiotherapy, including inherited syndromes
             associated with hypersensitivity to ionizing radiation (e.g., Ataxia-Telangiectasia,
             Nijmegen Breakage Syndrome)

          6. Patients with inadequate renal function or other contraindications to IV contrast

          7. Any previous treatment with PD-1 or PD-L1 inhibitors, including pembrolizumab

          8. Current or prior use of immunosuppressive medication within 28 days before the first
             dose of pembrolizumab, 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

          9. Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy

         10. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous
             immunotherapy agent, or any unresolved irAE >Grade 1

         11. Active or prior documented autoimmune disease within the past 2 years (subjects with
             vitiligo, Grave's disease, or psoriasis not requiring systemic treatment within the
             past 2 years are not excluded)

         12. Patients with evidence of interstitial lung disease or active, non-infectious
             pneumonitis

         13. History of primary immunodeficiency

         14. History of allogeneic organ transplant

         15. 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 or 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

         16. Severe, active co-morbidity, defined as follows:

               1. Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months

               2. Transmural myocardial infarction within the last 6 months

               3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration

               4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within 30 days of
                  registration

               5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

               6. Known history of active infection including tuberculosis

         17. Female patients who are pregnant or breastfeeding or male or female patients of
             reproductive potential who are not willing to employ effective birth control from
             screening to 90 days after the last dose of pembrolizumab.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tumor Response Rate
Time Frame:up to 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:up to 2 years
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:6 months
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:12 months
Safety Issue:
Description:
Measure:Incidence of post treatment toxicities
Time Frame:up to 2 years
Safety Issue:
Description:
Measure:Duration of Response
Time Frame:up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Oklahoma

Trial Keywords

  • QUADSHOT
  • Head and Neck Cancer
  • Pembrolizumab

Last Updated

May 1, 2020