Clinical Trials /

De-Escalation Therapy for Human Papillomavirus Negative Disease

NCT03944915

Description:

This study is looking to see if nivolumab, an immunotherapy drug, given with carboplatin and paclitaxel (2 chemotherapy agents) during induction therapy in advanced stage HPV negative patients can significantly shrink the subject's cancer.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: De-Escalation Therapy for Human Papillomavirus Negative Disease
  • Official Title: A Phase II Trial of Carboplatin, Paclitaxel, and Nivolumab Induction Therapy Followed by Response-stratified Locoregional Therapy for Patients With Locally Advanced, HPV-negative Head and Neck Cancer. The DEPEND Trial.

Clinical Trial IDs

  • ORG STUDY ID: IRB19-0162
  • NCT ID: NCT03944915

Conditions

  • Human Papilloma Virus
  • Squamous Cell Carcinoma
  • Squamous Cell Carcinoma of the Head and Neck
  • HPV-Related Squamous Cell Carcinoma
  • HNSCC

Interventions

DrugSynonymsArms
CarboplatinARM 1
PaclitaxelARM 1
NivolumabARM 1
Hydroxyurea PillARM 2
5-fluorouracil5-FUARM 2
Filgrastim InjectionFilgrastim shotARM 2
CisplatinARM 2

Purpose

This study is looking to see if nivolumab, an immunotherapy drug, given with carboplatin and paclitaxel (2 chemotherapy agents) during induction therapy in advanced stage HPV negative patients can significantly shrink the subject's cancer.

Trial Arms

NameTypeDescriptionInterventions
ARM 1ExperimentalInduction Therapy
  • Carboplatin
  • Paclitaxel
  • Nivolumab
ARM 2ExperimentalRadiation therapy with chemotherapy
  • Paclitaxel
  • Hydroxyurea Pill
  • 5-fluorouracil
  • Filgrastim Injection
  • Cisplatin

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must have pathologically confirmed locally advanced, non-metastatic,
             HPV-negative head and neck squamous cell carcinoma of the oral cavity, oropharynx,
             hypopharynx, nasopharynx, larynx, or sinuses.

          2. Stage IV disease with the exception of nasopharyngeal tumor-3, node-2 (stage III)
             based of American Joint Committee on Cancer staging 8th edition

          3. If a primary oropharyngeal squamous cell carcinoma is diagnosed, HPV must be ruled out
             by immunohistochemistry.

          4. Availability of ≥10 unstained 5 micron slides. Patients who cannot fulfill this
             requirement will need to undergo a new biopsy prior to enrollment on study.

          5. Patients must be at least 18 years of age.

          6. Measurable disease (either primary site and/or nodal disease) by RECIST criteria.

          7. No previous radiation or chemotherapy for a head and neck cancer.

          8. No complete surgical resection for a head and neck cancer within 8 weeks of enrollment
             (although lymph node biopsy including excision of an individual node with presence of
             residual nodal disease, or surgical biopsy/excision of the tumor with residual
             measurable disease is acceptable.) No surgical procedures or biopsies will occur after
             baseline scans are performed and measurable lesions are identified.

          9. Eastern Cooperative Oncology Group performance status 0-1

         10. Normal Organ Function

               1. Leukocytes ≥ 3000/mm3

               2. Platelets ≥ 100,000/mm3

               3. Absolute neutrophil count ≥ 1,500

               4. Hemoglobin ≥ 9.0 gm/dL

               5. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5x upper
                  limit of normal

               6. Alkaline phosphatase ≤ 2.5x upper limit of normal

               7. Albumin > 2.9 gm/dL

               8. Total bilirubin ≤ 1.5 mg/dL

               9. Creatinine clearance > 45 mL/min, normal within 2 weeks prior to start of
                  treatment (Of note, the standard Cockcroft and Gault formula must be used to
                  calculate creatinine clearance (CrCl) for enrollment or dosing)

         11. Patients must sign a study-specific informed consent form prior to study entry.
             Patients should have the ability to understand and the willingness to sign a written
             informed consent document.

         12. Women of childbearing potential must have a negative serum or urine pregnancy test
             (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the
             start of study drug

         13. Women must not be breastfeeding

         14. Women of childbearing potential must agree to follow instructions for method(s) of
             contraception for the duration of treatment with study drug(s) plus 6 months after
             completing chemoradiation or receiving the last dose of consolidative nivolumab,
             whichever occurs latest.

         15. Men who are sexually active with women of childbearing potential must agree to follow
             instructions for method(s) of contraception for the duration of treatment with study
             drug(s) plus 6 months after completing chemoradiation or receiving the last dose of
             consolidative nivolumab, whichever occurs latest.

        Exclusion Criteria:

          1. Unequivocal demonstration of distant metastatic disease (M1 disease).

          2. Unidentifiable primary site.

          3. Inter-current medical illnesses which would impair patient tolerance to therapy or
             limit survival. This includes but is not limited to ongoing or active infection,
             immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction,
             cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance. Patients with clinically stable
             and/or chronically managed medical illnesses that are not symptomatic and/or are not
             expected to impact treatment on protocol are still eligible (conditions to be reviewed
             by the PI to confirm eligibility)

          4. Prior surgical therapy other than incisional/excisional biopsy or organ-sparing
             procedures such as debulking of airway-compromising tumors. Residual measurable tumor
             is required for enrollment as discussed above.

          5. Patients receiving other investigational agents.

          6. Diagnosis of immunodeficiency or is receiving systemic steroid therapy in excess of
             physiologic dose or any other form of immunosuppressive therapy within 7 days prior to
             the first dose of trial treatment.

          7. Known history of active tuberculosis (Bacillus Tuberculosis infection).

          8. Hypersensitivity to nivolumab or any other drug used in this protocol.

          9. Prior systemic anti-cancer treatment within the last 8 weeks.

         10. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer or any
             tumors that are not likely to influence life expectancy in the subsequent 3 years
             without active treatment.

         11. Has active autoimmune disease that has required systemic therapy in the past year
             (i.e. with steroids or immunosuppressive drugs). Replacement therapy e.g.
             levothyroxine, insulin, or physiologic corticosteroid doses for adrenal or pituitary
             insufficiency, etc. are not considered a form of systemic treatment.

         12. Has known history of, or any evidence of active, non-infectious pneumonitis.

         13. Has a history of HIV.

         14. Has known active Hepatitis B or hepatitis C. If eradicated, patient is eligible.

         15. Has received a live vaccine within 28 days of planned start of study therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Deep Response Rate (DRR)
Time Frame:2 years
Safety Issue:
Description:DRR is 50% or greater response to induction therapy based on RECIST criteria. The objective is to intensify induction chemotherapy with the addition of an immune checkpoint inhibitor aimed at increasing the proportion of patients achieving a deep tumor response in order to subsequently allow risk-adapted definitive chemoradiotherapy in advanced stage HPV negative head and neck squamous cell cancer patients.

Secondary Outcome Measures

Measure:Progression Free Survival rate (PFS)
Time Frame:24 months
Safety Issue:
Description:Progression free survival at 24 months after completing chemoradiation. PFS will be defined as the time from registration to the date of the first documented disease progression, clinical progression, or death due to any cause, whichever occurs first.
Measure:Overall Survival rate (OS)
Time Frame:24 months
Safety Issue:
Description:Overall survival will be defined as the time between the date of registration and the date of death.
Measure:Locoregional control after completing chemoradiation
Time Frame:24 months
Safety Issue:
Description:assess disease control in all patients receiving induction chemoimmunotherapy and compare disease control between radiation arms.
Measure:Distant control after completing chemoradiation
Time Frame:24 months
Safety Issue:
Description:Distant control will be defined as the time from registration to the date of the first documented disease progression below the clavicles. Comparison between the two radiation arms will be made.

Details

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

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