Clinical Trials /

NKTR With Radiation for Head and Neck Squamous Cell Carcinoma

NCT04936841

Description:

This trial will evaluate safety and efficacy of the combination of anti-PD1, NKTR-214, and palliative radiation therapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Twenty-four participants will be enrolled to evaluate the efficacy of this combination.

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: NKTR With Radiation for Head and Neck Squamous Cell Carcinoma
  • Official Title: Phase II Study of Bempegaldesleukin (NKTR-214) Together With Palliative Radiation and Anti-PD-1 Checkpoint Blockade in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Clinical Trial IDs

  • ORG STUDY ID: UW20092
  • SECONDARY ID: A533300
  • SECONDARY ID: SMPH/HUMAN ONCOLOGY
  • SECONDARY ID: Protocol Version 4/19/2021
  • SECONDARY ID: 2021-0141
  • NCT ID: NCT04936841

Conditions

  • Head and Neck Cancer

Interventions

DrugSynonymsArms
NKTR-214bempegaldesleukinNKTR-214, anti-PD therapy plus Palliative Radiation
anti-PD-1 therapyPembrolizumabNKTR-214, anti-PD therapy plus Palliative Radiation

Purpose

This trial will evaluate safety and efficacy of the combination of anti-PD1, NKTR-214, and palliative radiation therapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Twenty-four participants will be enrolled to evaluate the efficacy of this combination.

Detailed Description

      Following an informed consent process, participants will receive anti-PD-1 therapy with 200
      mg of pembrolizumab and NKTR-214 at 0.006 mg/ml. Palliative radiation therapy will then be
      delivered to tumor sites causing or felt by the treating physician to have a high potential
      for causing symptoms with either 8 Gy X 3 or 4 Gy X 5 completed 3 to 7 days prior to cycle 2
      of anti-PD1 and NKTR-214. Combined anti-PD-1 and NKTR-214 will then be delivered each
      subsequent cycle.

      Efficacy will be measured by overall response rate (ORR), progression free survival (PFS),
      overall survival (OS), clinical benefit (CB), and duration of response with ORR the primary
      outcome being compared to historical control data. Toxicity will be evaluated prior to
      administration of each 21-day cycle, while receiving NKTR-214 followed by every four months
      after the participant is off trial. Health related quality of life questionnaires will be
      completed with cycle 1 and 2 and then every 4 cycles thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
NKTR-214, anti-PD therapy plus Palliative RadiationExperimentalCycle 1 consists of anti-PD-1 therapy (200mg) and NKTR-214 (0.006 mg/kg3 administered intravenously), followed by palliative radiation (8 Gy x 3 or 4 Gy x 5 fractions) combined with anti-PD-1 therapy and NKTR-214 in cycle 2. In subsequent cycles participants will receive NKTR-214 and anti-PD-1.
  • NKTR-214
  • anti-PD-1 therapy

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent and HIPAA authorization for release of personal health
             information. NOTE: HIPAA authorization may be included in the informed consent or
             obtained separately

          -  Qualify for anti-PD-1 therapy based on current guidelines at the time of registration.
             This includes the standard requirement for the participant's tumor to have been
             previously determined to express PD-L1 with a combined positive score ≥ 1, as
             determined by an FDA-approved test.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 30 days
             prior to enrollment

          -  Histologically proven diagnosis of head and neck squamous cell carcinoma that is
             metastatic or recurrent disease that is surgically incurable

          -  Prior cancer treatment other than anti-PD-1 therapy must be completed at least 30 days
             prior to registration and the participant must have recovered from all reversible
             acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline.
             Participants may not undergo concurrent anti-cancer treatment during treatment with
             protocol therapies. This includes no treatment with growth factors, tyrosine kinase
             inhibitors, tumor-specific antibodies, or cytotoxic chemotherapies such as cisplatin.
             Participants who have previously or are currently taking an anti-PD-1 therapy are
             eligible for this study if they meet eligibility criteria 2. Participants who have
             previously taken any other immune checkpoint inhibitor are eligible as long as they
             have completed that treatment at least 30 days prior to registration and meet all
             other eligibility criteria.

          -  Participants with central nervous system (CNS) metastases are eligible if the CNS
             lesions are stable for at least 2 months and if tapered off treatment doses of
             systemic corticosteroids for at least 2 weeks prior to enrollment on the trial.
             Management with maintenance physiologic doses of corticosteroids (equivalent doses of
             prednisone ≤ 10 mg daily) is acceptable.

          -  Participants must have an "index" tumor that: 1) is deemed by the treating radiation
             oncologist to potentially benefit from palliative radiation 2) is amenable to biopsy,
             3) is ≥ 1 cm in longest dimension.

          -  Demonstrate adequate organ function as defined in the table below; all screening labs
             to be obtained within 30 days prior to enrollment

               -  White blood cell (WBC) ≥ 3,000/mm3

               -  Absolute Neutrophil Count (ANC) ≥ 1,500/mm3

               -  Hemoglobin (Hgb) ≥ 9 g/dL

               -  Platelets ≥ 100,000/mm3

               -  Serum creatinine ≤ 2.0 mg/dL

               -  Total Bilirubin ≤ 2.0 × upper limit of normal (ULN) (< 3.0 for subjects with
                  Gilbert's Syndrome)

               -  Aspartate aminotransferase (AST) ≤ 3 × ULN

               -  Alanine aminotransferase (ALT) ≤ 3 × ULN

          -  Females of childbearing potential must have a negative serum pregnancy test within 14
             days prior to enrollment and must agree to use effective contraception during active
             treatment and for 5 months after last dose of pembrolizumab and/or NKTR-214. NOTE:
             Females are considered of childbearing potential unless they are surgically sterile
             (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)
             or they are naturally postmenopausal for ≥ 12 consecutive months.

          -  As determined by the enrolling physician or protocol designee, ability of the
             participant to understand and comply with study procedures for the entire length of
             the study

        Exclusion Criteria:

          -  Subjects with significant intercurrent illnesses per physician discretion

          -  Subjects with active or acute infections or active peptic ulcers, unless these
             conditions are adequately corrected or controlled, in the opinion of the treating
             physician

          -  Subjects with a diagnosed auto-immune disease (exceptions: subjects with controlled
             diabetes mellitus type I, thyroid disease, rheumatoid arthritis, vitiligo and alopecia
             areata not requiring treatment with immunosuppressants are eligible)

               -  Subjects with a history of diabetes mellitus requiring systemic therapy within
                  the past 3 months (i.e. either oral hypoglycemic agents or insulin) must have a
                  documented Hemoglobin A1c < 8.0 % within 90 days of registration.

          -  Subjects with known genetic conditions causing pre-disposition to radiotherapy (RT)
             toxicity (i.e.: Li-Fraumeni, ATM deficiency, active scleroderma, etc.)

          -  Participants with a prior diagnosis of cerebrovascular accident (CVA) or transient
             ischemic attack (TIA)

          -  Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
             mother is being treated on study)

          -  Known additional malignancy that is active and/or progressive requiring treatment;
             exceptions include basal cell or squamous cell skin cancer, in situ cervical or
             bladder cancer, or other cancer for which the subject has been disease-free for at
             least three years prior to enrollment

          -  Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for
             women at time of enrollment

          -  Subjects with symptoms of ischemic cardiac disease, congestive heart failure, or
             myocardial infarction within 6 months of registration and/or uncontrolled cardiac
             rhythm disturbance

          -  Subjects with a pulmonary embolism, deep vein thrombosis, or prior clinically
             significant venous or non-CVA/TIA arterial thromboembolic event (e.g., internal
             jugular vein thrombosis) within 3 months prior to enrollment

               -  Patients with a history of a venous or arterial thromboembolic event must be
                  asymptomatic prior to enrollment and must be receiving a stable regimen of
                  therapeutic anticoagulation (low molecular weight heparin (LMWH) or direct oral
                  anticoagulation (DOAC)). Use of coumadin is permitted; however, therapeutic
                  dosing should target a specific international normalized ratio (INR) stable for
                  at least 4 weeks prior to enrollment. NKTR-214 has the potential to down-regulate
                  metabolizing enzymes for coumadin for approximately 1 week after administration
                  of each dose of NKTR-214. Due to the possibility of drug-drug interactions
                  between coumadin and NKTR-214, frequent monitoring of INR and ongoing
                  consideration of dose adjustments are warranted throughout the patient's
                  participation on study.

          -  Subjects with significant psychiatric disabilities or seizure disorders if considered
             unsafe in the opinion of the treating physician

          -  Subjects with symptomatic pleural effusions or ascites

          -  Subjects with organ allografts

          -  Subjects who require, or are likely to require, systemic treatment doses of
             corticosteroids, or other immunosuppressive drugs, or have used them within 2 weeks of
             registration (clarification: subjects receiving physiologic maintenance or replacement
             doses of systemic steroids or inhaled steroids are eligible)

          -  Subjects with known human immunodeficiency virus (HIV) infection, active or chronic
             hepatitis B or hepatitis C infection, or with clinical evidence of hepatitis 15.
             Subjects with known hypersensitivity to IL2 or those who experienced significant
             immune-related AEs requiring treatment with steroids or other immunosuppressant
             therapy during prior treatment with ipilimumab, or anti- PD-1/PD-L1 checkpoint
             blockade therapy 16. Subjects who cannot provide independent, legal, informed consent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:up to 7 months (at Standard-of-care imaging 3 to 6 months after Cycle 1)
Safety Issue:
Description:ORR is the percentage of participants whose cancer shrinks or disappears after treatment. ORR will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST1.1, by investigator assessment.

Secondary Outcome Measures

Measure:Adverse Events Greater than or equal to Grade 3
Time Frame:up to 5 years
Safety Issue:
Description:Toxicities ≥ Grade 3 is defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicities not "unrelated" to treatment, will be considered treatment-related.
Measure:Progression Free Survival (PFS)
Time Frame:up to 5 years
Safety Issue:
Description:PFS is the average length of time after the start of treatment in which a person is alive, and their cancer does not grow or spread. PFS is defined as the time from day 1 of treatment until the criteria for disease progression is met as defined by RECIST1.1 or death as a result of any cause.
Measure:Overall Survival (OS)
Time Frame:up to 5 years
Safety Issue:
Description:OS is defined as time from day 1 of treatment until death as a result of any cause.
Measure:Clinical Benefit (CB)
Time Frame:up to 5 years
Safety Issue:
Description:CB will include confirmed complete response (CR) + confirmed partial response (PR) + stable disease at ≥ 6 months (SD) and will be determined as per RECIST1.1.
Measure:Duration of Response
Time Frame:up to 5 years
Safety Issue:
Description:Duration of response is the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented.
Measure:Health Related Quality of Life as measured by EORTC QLQ-C30 Score
Time Frame:up to 5 years
Safety Issue:
Description:European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is a 30 item instrument with a total possible range of scores 30 - 126, where lower scores indicate improved quality of life.
Measure:Health Related Quality of Life as measured by EORTC QLQ-H&N35 Score
Time Frame:up to 5 years
Safety Issue:
Description:European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire - Head and Neck (EORTC QLQ-H&N35) is a 35 item instrument where 30 items are scored 1 (not at all) 2 (a little) 3 (quite a bit) and 4 (very much), and 5 items are scored 1 (no) and 2 (yes), for a total possible range of scores between 35 - 130 where lower scores indicate better health related quality of life.
Measure:Health Related Quality of Life as measured by EQ-5D Score
Time Frame:up to 5 years
Safety Issue:
Description:The EQ-5D is a 5 question measure of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression plus an overall measure of health reported on a visual analog scale. Scores are normalized between 1 (full health) and 0 (dead).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Wisconsin, Madison

Last Updated

June 23, 2021