Clinical Trials /

Quad Shot Radiotherapy in Combination With Immune Checkpoint Inhibition

NCT04454489

Description:

This is a single-arm, non-randomized pilot study to evaluate the efficacy and tolerability of combination quad-shot palliative radiotherapy with immunotherapy for advanced/recurrent/metastatic head and neck cancer.

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 in Combination With Immune Checkpoint Inhibition
  • Official Title: Quad-Shot Radiotherapy in Combination With Immune Checkpoint Inhibition for Advanced/Recurrent Head and Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB00066650
  • SECONDARY ID: WFBCCC 60320
  • SECONDARY ID: P30CA012197
  • NCT ID: NCT04454489

Conditions

  • Advanced Head and Neck Squamous Cell Carcinoma
  • Recurrent Head and Neck Squamous Cell Carcinoma
  • Metastatic Head-and-neck Squamous-cell Carcinoma

Interventions

DrugSynonymsArms
Pembrolizumab (immunotherapy)Quad-shot palliative radiotherapy and Immunotherapy

Purpose

This is a single-arm, non-randomized pilot study to evaluate the efficacy and tolerability of combination quad-shot palliative radiotherapy with immunotherapy for advanced/recurrent/metastatic head and neck cancer.

Detailed Description

      Primary Objective: Measure the overall response rate for immunotherapy given with quad-shot
      radiotherapy.

      Secondary Objective(s)

        -  Measure the response rate at the target lesion.

        -  Measure the response rate at non-target sites in patients with non-target sites.

        -  Evaluate the durability of response at the target lesion.

        -  Evaluate progression-free survival.

        -  Evaluate overall survival.

        -  Assess the tolerability of the combination of quad-shot radiotherapy with immunotherapy
           in order to assess the feasibility of this treatment regimen.

      Exploratory Objective: Evaluate the effect of quad- shot administration on increasing the
      immune activation by treatment with pembrolizumab and investigate possible mechanisms.
    

Trial Arms

NameTypeDescriptionInterventions
Quad-shot palliative radiotherapy and ImmunotherapyExperimentalSystemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively
  • Pembrolizumab (immunotherapy)

Eligibility Criteria

        Inclusion Criteria:

          -  Advanced, recurrent or metastatic head and neck squamous cell carcinoma, as defined by
             clinical or pathological diagnosis of any of the following:

          -  Locally advanced head and neck squamous cell carcinoma not suitable for curative local
             treatment.

          -  Locally recurrent head and neck squamous cell carcinoma not suitable for curative
             local treatment within or outside a previously irradiated tissue.

          -  Metastatic head and neck squamous cell carcinoma.

          -  Target site in the head and neck region amenable to quad-shot palliative radiotherapy,
             as determined by the treating radiation oncologist.

          -  Age 18 years or greater at time of registration.

          -  ECOG Performance Status of 0-2.

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately.

          -  Ability to understand and the willingness to sign an IRB-approved informed consent
             document (either directly or via a legally authorized representative).

          -  Willingness to provide blood and saliva samples for exploratory research purposes.

          -  Organ and Marrow Function as defined below: Absolute neutrophil count (ANC) ≥ 1.5 x
             109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 9.0 g/dL, serum bilirubin ≤ 1.5 x
             ULN (institutional upper limit of normal), AST and ALT ≤ 2.5 x ULN (institutional
             upper limit of normal), serum creatinine CL>40 mL/min by the Cockcroft-Gault formula
             (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of
             creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age)
             (divided by) 72 x serum creatinine (mg/dL). Females: Creatinine CL (mL/min) = Weight
             (kg) x (140 - Age) x 0.85 (divided by) 72 x serum creatinine (mg/dL)

        Exclusion Criteria:

          -  Radiation therapy to the head and neck region within 30 days of registration.

          -  Prior radiotherapy to the head and neck that precludes safe delivery of study
             radiotherapy, as determined by the treating radiation oncologist.

          -  Active medical conditions that are contraindications to study radiotherapy (i.e.
             scleroderma), as determined by the treating radiation oncologist.

          -  Pregnant or lactating women are excluded from this study because radiotherapy is
             contraindicated in pregnancy and because there is an unknown but potential risk for
             adverse events in nursing infants secondary to treatment of the mother with
             immunotherapy.

          -  Participation in another clinical study with an investigational product during the
             last 3 months.

          -  Any previous treatment with a PD1 or PD-L1 inhibitor.

          -  Any anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted
             therapy, biologic therapy, tumor embolization, monoclonal antibodies, other
             investigational agent) within the last 30 days.

          -  Mean QT interval corrected for heart rate (QTc) ≥470 ms.

          -  Current or prior use of immunosuppressive medication within 30 days, with 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.

          -  Any unresolved toxicity (>CTCAE grade > 2) from previous anti-cancer therapy. Subjects
             with irreversible toxicity that is not reasonably expected to be exacerbated by the
             investigational product may be included (e.g., hearing loss, peripherally neuropathy).

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

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

          -  Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
             ulcerative colitis).

          -  History of primary immunodeficiency.

          -  History of allogeneic organ transplant.

          -  History of hypersensitivity to any excipient in pembrolizumab.

          -  History of pneumonitis or interstitial lung disease.

          -  Subjects with uncontrolled seizures.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, uncontrolled cardiac arrhythmia, active peptic ulcer disease or
             gastritis, active bleeding diatheses, 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.

          -  Known history of active tuberculosis.

          -  Receipt of live attenuated vaccination within 30 days prior to study entry or within
             30 days of receiving pembrolizumab.

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of study treatment or interpretation of patient safety or study results.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response
Time Frame:Up to 30 weeks at cycle 10 (each cycle is 3 weeks) weeks after start of intervention
Safety Issue:
Description:Overall response will be measured according to RECIST 1.1 criteria to determine the percentage of participants with either a partial or complete response and the corresponding 95% Clopper-Pearson exact confidence interval. The best overall response is the best response recorded from the start of the treatment across all time points.

Secondary Outcome Measures

Measure:Response Rate in the Target Lesions
Time Frame:Up to 30 weeks at cycle 10 (each cycle is 3 weeks) weeks after start of intervention
Safety Issue:
Description:Response rate will be measured as the following: Complete: Disappearance (or decrease to the point at which measurement is not possible) of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial: At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease: Greater than 20% increase in the sum of the longest diameters (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 mm increase over the nadir. When sum becomes very small, increases within measurement error (2-3 mm) can lead to 20% increase. Stable Disease: Greater than 20% increase in the sum of the longest diameters (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 mm increase over the nadir. When sum becomes very small, increases within measurement error (2-3 mm) can lead to 20% increase.
Measure:Response Rate in the Non-Target Lesions
Time Frame:Up to 30 weeks at cycle 10 (each cycle is 3 weeks) weeks after start of intervention
Safety Issue:
Description:Response rate will be measured using RECIST 1.1: Complete: Disappearance (or decrease to the point at which measurement is not possible) of all non-target lesions. All lymph nodes must be non-pathological in size (< 10 mm short axis). Partial: Non-complete response/Non-progressive disease: Persistence of 1 or more non-target lesion(s). Progressive Disease: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. Stable Disease: Greater than 20% increase in the sum of the longest diameters (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 mm increase over the nadir. When sum becomes very small, increases within measurement error (2-3 mm) can lead to 20% increase.
Measure:Duration of Response at the Target Lesions - Mean Measurement
Time Frame:Up to 30 weeks at cycle 10 (each cycle is 3 weeks) weeks after start of intervention
Safety Issue:
Description:For the duration of response, among participants investigators will estimate both the mean duration and the corresponding 95% confidence intervals for the mean and inter-quartile range for the median.
Measure:Duration of Response at the Target Lesions - Median Measurement
Time Frame:Up to 30 weeks at cycle 10 (each cycle is 3 weeks) weeks after start of intervention
Safety Issue:
Description:For the duration of response, among participants investigators will estimate the median duration and the corresponding 95% confidence intervals for the mean and inter-quartile range for the median.
Measure:Percentage of Participants with Progression-Free Survival
Time Frame:At 6 months and 1 year post treatment
Safety Issue:
Description:For progression-free survival investigators will estimate Kaplan Meier survival curves and the median time to progression-free survival.
Measure:Percentage of Participants with Overall Survival
Time Frame:At 6 months and 1 year post treatment
Safety Issue:
Description:For time to event measure of overall survival investigators will estimate Kaplan Meier survival curves and the median time to overall survival.
Measure:Incidences of Adverse Events
Time Frame:Up to 2 months after last study drug administered
Safety Issue:
Description:Tolerability of intervention will be assessed using Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Event (PRO CTCAE). Investigators will estimate the percentage of patients with different adverse events using a 95% Clopper Pearson exact confidence level.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Wake Forest University Health Sciences

Last Updated

June 26, 2020