Summary

for people ages 18 years and up (full criteria)
at San Francisco, California
study started
estimated completion:
Alain Algazi

Description

Summary

To determine the effect of neoadjuvant atezolizumab alone or in combination with emactuzumab, CPI-444, and other immune modulating agents on T-cell infiltration in advanced SCCHN. To determine the impact of neo-adjuvant immunotherapy on surgical outcomes.

Official Title

A Phase II Study of Perioperative Immunotherapy in Patients With Advanced Non-Virally Associated Squamous Cell Carcinoma of the Head and Neck

Details

PRIMARY OBJECTIVES:

  1. To determine the effect of neoadjuvant atezolizumab alone or in combination with emactuzumab and other immune modulating agents on T-cell infiltration in advanced squamous cell carcinoma of the head and neck (SCCHN). (Translational) II. To determine the impact of neo-adjuvant immunotherapy on surgical outcomes. (Clinical)

SECONDARY OBJECTIVES:

  1. To associate changes in CD3 infiltration with radiographic response in the surgical window. (Translational) II. To describe the changes in T-cell subtypes and other mediators of anti-tumor immune response induced by neoadjuvant atezolizumab alone or in combination with emactuzumab or other immune-modulating agents in advanced SCCHN patients. (Translational) III. To describe the impact of neoadjuvant, surgical, and adjuvant therapy on peripheral immune responses. (Translational) IV. To determine whether combined neo-adjuvant and adjuvant immune therapy improves 2-year relapse-free survival (RFS) in patients with SCCHN. (Clinical) V. To establish the safety/toxicity profile of each regimen in the perioperative and postoperative settings for patients with advanced SCCHN. (Clinical)

EXPLORATORY OBJECTIVES:

  1. To establish immune-competent tumor xenograft models for future research. II. To characterize changes in the gut microbiome associated with each therapeutic combination.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes every 3 weeks for up to 2 courses prior to standard surgery and radiation. 16 weeks post-surgery, patients receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive atezolizumab IV over 30-60 minutes and emactuzumab IV over 90 minutes every 3 weeks for up to 2 courses prior to standard surgery and radiation. 16 weeks post-surgery, patients receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days and then periodically for up to 2 years.

IV. To determine whether combined neo-adjuvant and adjuvant immune therapy improves 2-year relapse-free survival (RFS) in patients with SCCHN. (Clinical) V. To establish the safety/toxicity profile of each regimen in the perioperative and postoperative settings for patients with advanced SCCHN. (Clinical)

EXPLORATORY OBJECTIVES:

  1. To establish immune-competent tumor xenograft models for future research. II. To characterize changes in the gut microbiome associated with each therapeutic combination.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes every 3 weeks for up to 2 courses prior to standard surgery and radiation. 16 weeks post-surgery, patients receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive atezolizumab IV over 30-60 minutes and emactuzumab IV over 90 minutes every 3 weeks for up to 2 courses prior to standard surgery and radiation. 16 weeks post-surgery, patients receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days and then periodically for up to 2 years.

Keywords

Cancer Carcinoma Squamous Cell Carcinoma Head and Neck Cancer Non-Virally Associated Squamous Cell Carcinoma Head and Neck Carcinoma, Squamous Cell Head and Neck Neoplasms Atezolizumab Antibodies, Monoclonal Emactuzumab Atezolizumab and Emactuzumab

Eligibility

You can join if…

Open to people ages 18 years and up

  • Patients must have histologically or cytologically confirmed stage III or stage IV SCCHN that is amenable to surgical resection with curative intent. Primary tumors in the oropharynx must test negative for human papillomavirus (HPV). Primary tumors in the nasopharynx must test negative for Epstein-Barr virus (EBV). Tumors originating outside of the oropharynx and nasopharynx will be presumed to be virus negative
  • Patients must agree to undergo post-surgery adjuvant radiation therapy with or without concurrent, weekly cisplatin at 40 mg/m2 (as clinically indicated)
  • Be willing and able to provide written informed consent/assent for the trial
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)1.1
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion prior to the initiation of neoadjuvant treatment on protocol
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)performance scale
  • Absolute neutrophil count (ANC) >=1,500 /mcL (performed within 14 days of treatment initiation)
  • Platelets >=100,000 / mcL (performed within 14 days of treatment initiation)
  • Hemoglobin >= 9 g/dL (performed within 14 days of treatment initiation)
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for subject with creatinine levels > 1.5 x institutional ULN (performed within 14 days of treatment initiation)
  • Creatinine clearance should be calculated per institutional standard
  • Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 14 days of treatment initiation)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases (performed within 14 days of treatment initiation)
  • Albumin >= 2.5 mg/dL (performed within 14 days of treatment initiation)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 14 days of treatment initiation)
  • Activated partial thromboplastin rime (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 14 days of treatment initiation)
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential must be willing to use an adequate method of contraception - Contraception, for the course of the study through 5 months after the last dose of study medication
  • Male subjects must agree to use an adequate method of contraception. Contraception,starting with the first dose of study therapy through 5 months after the last dose of study therapy * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

You CAN'T join if...

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Contraindication at study enrollment to adjuvant radiation therapy
  • Has a known history of active TB (Bacillus tuberculosis)
  • Hypersensitivity to atezolizumab, emactuzumab or any of their excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) 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
  • Has had prior targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent or radiation therapy
  • 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, in situ cervical cancer,low-grade thyroid cancer and indolent prostate cancer. Additional malignancies may be permitted after consultation with the principal investigator Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has known history of, or any evidence of active, non-infectious pneumonitis requiring corticosteroids
  • Patient has known history of stage 2 or higher chronic obstructive pulmonary disease(COPD). Stage 2 COPD is defined as forced expiratory volume in one second(FEV1)/forced vital capacity (FVC) < 70%; 50% < FEV1 < 80% predicted, with dyspnea on exertion
  • Patient has asthma requiring systemic corticosteroids at the time of screening.Inhaled corticosteroids for the treatment of asthma are permitted
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] quantitative has been detected). HBsAg reactive on appropriate antiviral therapy with suppressed hepatitis B virus (HBV) deoxyribonucleic acid (DNA) less than 100 and eligible liver function will be allowed
  • Current New York Heart Association (NYHA) class III or higher heart failure. Patients with a prior history of heart failure that has resolved to class II or lower may participate
  • Patient has been treated with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or is anticipated to need such a vaccine during the course of the study or within 5 months after the last dose of atezolizumab
  • Known human immunodeficiency virus positive (HIV+) patients may be included but must have:
  • A stable regimen of highly active anti-retroviral therapy (HAART)
  • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
  • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based tests

Location

  • University of San Francisco, California
    San Francisco California 94115 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT03708224
Phase
Phase 2
Lead Scientist
Alain Algazi
Study Type
Interventional
Last Updated