Clinical Trials /

HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma

NCT04369937

Description:

This clinical trial will evaluate a new combination of pembrolizumab, HPV-16 E6/E7 specific therapeutic vaccination (ISA101b) and cisplatin-based chemoradiotherapy for patients with newly diagnosed, local-regionally advanced, intermediate risk HPV-associated head and neck squamous cell carcinoma.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma of Unknown Primary
  • Oropharyngeal Squamous Cell Carcinoma
  • Tonsillar Squamous Cell Carcinoma
  • Well-Differentiated Thyroid Gland Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma
  • Official Title: Phase II Study Evaluating HPV-16 Vaccination (ISA101b) and Pembrolizumab Plus Cisplatin Chemoradiotherapy for "Intermediate Risk" HPV-16 Associated Head and Neck Squamous Cell Carcinoma (HNSCC)

Clinical Trial IDs

  • ORG STUDY ID: HCC 19-082
  • NCT ID: NCT04369937

Conditions

  • HPV-Related Squamous Cell Carcinoma
  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabIMRT + Pembrolizumab + Cisplatin + ISA101b
CisplatinIMRT + Pembrolizumab + Cisplatin + ISA101b
ISA101bHPV-16 VaccineIMRT + Pembrolizumab + Cisplatin + ISA101b

Purpose

This clinical trial will evaluate a new combination of pembrolizumab, HPV-16 E6/E7 specific therapeutic vaccination (ISA101b) and cisplatin-based chemoradiotherapy for patients with newly diagnosed, local-regionally advanced, intermediate risk HPV-associated head and neck squamous cell carcinoma.

Detailed Description

      This study aims to enroll 50 patients (male and female, age 18+) who have intermediate risk
      disease with histologically-confirmed head and neck squamous cell carcinoma with no evidence
      of distant metastasis. All patients will receive the same treatment and there is no active
      control group.

      In this trial, patients will undergo biopsy followed by treatment with ISA101b vaccine which
      will be initiated 2 weeks prior to cisplatin-IMRT, and one week prior to the first dose of
      pembrolizumab. Vaccines will continue for 2 additional administrations at weeks 2 and 5, on
      the same day as successive pembrolizumab infusions. Pembrolizumab will be initiated 1 week
      prior to cisplatin-IMRT at the dose of 200 mg IV q3 weeks (+/- 3 days). Pembrolizumab will be
      continued concurrently through cisplatin-IMRT (weeks 3, 6 ), and continued for a 15 week
      maintenance period after completion of cisplatin-IMRT for a total pembrolizumab treatment
      period of 24 weeks (8 doses; 6 months).
    

Trial Arms

NameTypeDescriptionInterventions
IMRT + Pembrolizumab + Cisplatin + ISA101bExperimentalIMRT (Intensity Modulated Radiotherapy) of 70 Gy in 35 fractions over 7 weeks (5 fractions per week). Pembrolizumab will be administered at 200 mg (fixed dose) IV every 3 weeks (+/- 3 days), beginning beginning one week (week -1) prior to concurrent cisplatin-IMRT. Cisplatin will be administered at 100 mg/m2 IV on days 1(Week 0) and 22 (Week 3). ISA101b will be administered as three rounds of vaccination 3-4 weeks apart via two SC injections per vaccination round at 100ug/peptide, before pembrolizumab treatment. Vaccination #1 will be administered 1 week before pembrolizumab.
  • Pembrolizumab
  • Cisplatin
  • ISA101b

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically-confirmed head and neck squamous cell carcinoma with no evidence of
             distant metastasis, with a primary site being the oropharynx. Squamous cell carcinoma
             of unknown primary, metastatic to cervical lymph nodes - patients can enroll provided
             all other eligibility criteria are met.

          -  Patients must have intermediate risk disease.

             o Patients must meet one of the following criteria: Oropharynx: p16(+) PLUS HPV ISH(+)
             (DNA or RNA) AND one of the following; ≥ AND ≥ 10 pack-years tobacco exposure (see
             Tobacco Assessment Form, Appendix A)

          -  T4 or N2c/N3 disease irrespective of tobacco exposure

          -  Unknown primary: p16(+) PLUS HPV ISH(+) (DNA or RNA) AND one of the following

          -  ≥ N2a AND ≥ 10 pack-years tobacco exposure

          -  N2c/N3 disease irrespective of tobacco exposure

          -  Patients should be considered not a candidate for curative-intent surgery with
             diagnosis of AJCC 7th edition Stage III, IVa, or IVb disease.

               -  Diagnostic simple palatine or lingual tonsillectomy is permitted, provided
                  patient has RECIST-measurable nodal disease.

               -  Patients with a second HNSCC primary tumor are eligible for this study, provided
                  more than 2 years have elapsed since the first diagnosis of HNSCC, the original
                  tumor was managed with surgery only (no adjuvant chemotherapy or radiotherapy),
                  and has not recurred.

          -  Patients with simultaneous primaries are excluded, with the exception of patients with
             bilateral tonsil/base of tongue HPV+ cancers or patients with T1-2, N0, M0
             differentiated thyroid carcinoma (resected or management deferred), who are eligible.

          -  No prior systemic (chemotherapy or biologic/molecular targeted therapy) or radiation
             treatment for head and neck cancer.

               -  Patients may have received chemotherapy or radiation for a previous, curatively
                  treated non-HNSCC malignancy, provided at least 2 years have elapsed.

               -  Patients must be untreated with radiation above the clavicles.

          -  Patients with a history of curatively-treated non-HNSCC malignancy must be
             disease-free for at least 2 years except for excised and cured disease.

          -  The patient must consent to a research biopsy at baseline. Optional biopsies during
             week 2 of pembrolizumab/ISA101b vaccination (prior to start of cisplatin-IMRT), in
             week 2 after the start of IMRT and within 2 weeks after starting CRT.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  Age ≥ 18

          -  Patients must have measurable disease according to RECIST 1.1

          -  Patients must demonstrate adequate organ function

          -  Written informed consent must be obtained from all patients prior to study
             registration.

          -  Documentation of negative pregnancy within 14 days prior to first dose.

        Exclusion Criteria:

          -  Oral Cavity, Larynx, Hypopharynx or Nasopharyngeal primary site

          -  Current participation in or previous participation in a study of an investigational
             agent or using an investigational device within 4 weeks of the first dose of study
             treatment.

          -  Prior treatment with anti-HPV agents except prevention HPV vaccines

          -  History of severe allergic or anaphylactic reactions or hypersensitivity to
             recombinant proteins or excipients in the investigational agents (pembrolizumab and
             ISA101b

          -  Distant metastatic disease including CNS or leptomeningeal metastases is not allowed.

          -  Acquired Immune Deficiency Syndrome (AIDS).

          -  Received prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not
             recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier.

          -  History of second malignancy within 2 years prior to Study Day 1 (except for excised
             and cured non-melanoma skin cancer, carcinoma in situ of breast or cervix, superficial
             bladder cancer, or T1a or T1b prostate cancer comprising < 5% of resected tissue with
             normal prostate specific antigen (PSA) since resection).

          -  Active autoimmune disease requiring systemic treatment within the past 3 months or a
             documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents.

          -  Acquired Immune Deficiency Syndrome (AIDS).

          -  Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Received a live vaccine within 30 days prior to the first dose of trial treatment.

          -  Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways).

          -  Significant pulmonary disease including pulmonary hypertension, history of
             (non-infectious) pneumonitis that required steroids, evidence of interstitial lung
             disease or active, non-infectious pneumonitis

          -  History or current evidence of any other medical or psychiatric condition, therapy, or
             laboratory abnormality not in the best interest of the trial or subject to
             participate, per the treating investigator.

          -  Peripheral neuropathy ≥ Grade 2

          -  Significant cardiovascular disease.

          -  Significant thrombotic or embolic events within 3 months prior to Study Day 1.

          -  Major surgery within 6 weeks prior to Study Day 1 (subjects must have completely
             recovered from any previous surgery prior to Study Day 1). Biopsy, diagnostic
             tonsillectomy, airway tumor debulking or excisional lymph node biopsy do not
             constitute major surgery.

          -  Active infection requiring antibiotics or antifungals within 7 days prior to first
             dose of study drug.

          -  Significant electrolyte imbalance prior to enrollment (note that patients may be
             supplemented to achieve acceptable electrolyte values):

          -  Pregnant or breastfeeding (due to potential for teratogenic or abortifacient effects).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free Survival (PFS) at 2 years
Time Frame:Up to 2 years
Safety Issue:
Description:The proportion of participants whose disease has to progressed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 2 years. PFS will be calculated from treatment initiation to disease progression or death from any cause for 2 years. Per RECIST 1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Secondary Outcome Measures

Measure:Adverse Events Related to Study Treatment
Time Frame:Up to 3 years
Safety Issue:
Description:The percentage of Serious Adverse Events per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 that are possibly, probably or definitely related to study treatment.
Measure:Progression-free Survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description:The length of time during and after the treatment that patients remain alive with disease that does not progress. PFS will be calculated from treatment initiation to disease progression or death from any cause or last follow up. Per RECIST 1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Measure:Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:The length of time (months) from the initiation of treatment that patients are still alive.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Robert Ferris

Trial Keywords

  • Head and Neck Squamous Cell Carcinoma (HNSCC)
  • HPV-16-associated HNSCC
  • ISA101b
  • Pembrolizumab
  • Cisplatin
  • Chemoradiotherapy

Last Updated

April 27, 2020