Preoperative Immunotherapy for Head and Neck Cancers
Recruiting in Palo Alto (17 mi)
Overseen byAlain Algazi, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Alain Algazi
Must not be taking: Immunosuppressants, Steroids, Monoclonal antibodies, others
Disqualifiers: Immunodeficiency, Active infection, Autoimmune disease, others
Stay on Your Current Meds
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?To determine the effect of neoadjuvant atezolizumab alone or in combination with other immune modulating agents on T-cell infiltration in advanced SCCHN. To determine the impact of neo-adjuvant immunotherapy on surgical outcomes.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these medications before starting the trial. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug Atezolizumab for head and neck cancers?
Research shows that Atezolizumab, which blocks a protein that helps cancer cells hide from the immune system, has been effective in treating various types of tumors, including head and neck cancer, by improving the body's immune response against the cancer.
12345Is atezolizumab safe for use in head and neck cancer treatment?
Atezolizumab has been studied for safety in head and neck cancer, showing it is generally safe for use in humans, with manageable side effects.
15678How does the drug used in preoperative immunotherapy for head and neck cancers differ from other treatments?
The drug used in preoperative immunotherapy for head and neck cancers may involve biologics like Omalizumab, which is unique because it targets IgE (a type of antibody involved in allergic reactions) and has been used in other conditions like asthma and allergic rhinitis to reduce symptoms by lowering IgE levels. This approach is different from traditional cancer treatments that typically focus on directly targeting cancer cells.
910111213Eligibility Criteria
Adults with suspected squamous cell carcinoma of the head and neck (SCCHN) that can be surgically removed. They must have good organ function, not be pregnant or breastfeeding, agree to use contraception, and have no recent cancer treatments or severe allergies to trial drugs. Excluded are those with active cancers elsewhere, certain heart conditions, immune diseases requiring treatment in the last 2 years, infections needing hospitalization recently, COPD stage 2+, known HIV without stable treatment or other conditions that may affect trial safety.Inclusion Criteria
Be willing and able to provide written informed consent/assent for the trial
Female subject of childbearing potential should have a negative urine or serum pregnancy within 7 days 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
I am 18 years old or older.
+6 more
Exclusion Criteria
I have active hepatitis B or C.
I have severe heart failure (NYHA class III or higher).
I have not received a live vaccine recently and do not plan to during the study.
+19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Neoadjuvant Treatment
Participants receive neoadjuvant atezolizumab alone or in combination with other immune-modulating agents for up to 15 days prior to definitive surgery
2 weeks
2 infusions (in-person)
Surgery and Radiation
Participants undergo definitive surgery followed by radiation therapy
Varies based on individual treatment plans
Adjuvant Treatment
For the first 9 participants in Arm A, adjuvant atezolizumab is administered every 3 weeks for up to 12 courses starting 16 weeks after surgery and radiation
36 weeks
12 infusions (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 months
Visits at 30 days post-surgery, 3 months, 6 months, 12 months, and 24 months
Participant Groups
The study is testing if pre-surgery immunotherapy with atezolizumab alone or combined with tocilizumab or tiragolumab can increase T-cell infiltration in SCCHN tumors. It also examines how these treatments affect surgery outcomes. Participants will receive one of these drug combinations before their scheduled surgery.
4Treatment groups
Experimental Treatment
Group I: Atezolizumab MonotherapyExperimental Treatment1 Intervention
Participants will receive 840mg of atezolizumab over 15 days prior to definitive surgery.
Group II: Atezolizumab + TocilizumabExperimental Treatment2 Interventions
Participants will receive 840 mg of atezolizumab IV and 6 mg/kg of Tocilizumab during the 15-day neoadjuvant period prior to definitive surgery.
Group III: Atezolizumab + TiragolumabExperimental Treatment2 Interventions
Participants will receive 840 mg of atezolizumab IV and 600 mg of Tiragolumab during the 15-day neoadjuvant period prior to definitive surgery.
Group IV: Atezolizumab (Adjuvant)Experimental Treatment1 Intervention
Participants will receive 840mg of atezolizumab over 15 days prior to definitive surgery. The first 9 participants in Arm A (atezolizumab monotherapy) will also receive adjuvant atezolizumab 16 weeks after standard of care surgery and radiation, or chemoradiation therapy, at a fixed dose of 1200 mg IV every 3 weeks for an additional 12 cycles.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of San Francisco, CaliforniaSan Francisco, CA
Loading ...
Who Is Running the Clinical Trial?
Alain AlgaziLead Sponsor
American Head and Neck SocietyCollaborator
Genentech, Inc.Industry Sponsor
References
Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. [2022]Head and neck cancer (HNC) has a poor prognosis at advanced stages. Given the immunosuppressive tumor microenvironment in HNC, inhibition of the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling pathway represents a promising therapeutic approach. Atezolizumab (anti-PD-L1) is efficacious against many tumor types. Here we report the clinical safety and activity from the HNC cohort of the phase Ia PCD4989g clinical trial.
Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. [2022]Given the recent successes of anti-PD-1 immunotherapy, many clinical trials have sought to assess the safety and efficacy of this treatment modality in the neoadjuvant setting. This systematic review provides a comprehensive summary of findings from neoadjuvant head and neck cancer immunotherapy clinical trials with a focus on PD-1/PD-L1 axis blockade. Pubmed, Embase, Cochrane Library, Web of Science, Google Scholar, and clinicaltrials.gov were systematically searched for all eligible neoadjuvant head and neck cancer immunotherapy clinical trials. Eight clinical trials met the inclusion criteria comprising a total of 260 patients. Study drugs included nivolumab, pembrolizumab, ipilimumab, durvalumab, and tremelimumab. The overall mean objective response rate (ORR) was 45.9 ± 5.7% with a 41.5 ± 5.6% single agent mean ORR. There were no deaths due to immune-related toxicities. Neoadjuvant immunotherapy for mucosal head and neck squamous cell cancer has demonstrated favorable response rates with no unexpected immune-related toxicities in phase I/II clinical trials.
Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. [2021]The prognosis for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is poor, and only a minority of patients benefit from checkpoint immunotherapy. Talimogene laherparepvec (T-VEC), an oncolytic immunotherapy approved for advanced melanoma, in combination with pembrolizumab may yield enhanced antitumor activity over either agent alone.
Real-world Data of Palliative First-line Checkpoint Inhibitor Therapy for Head and Neck Cancer. [2023]Pembrolizumab alone or combined with chemotherapy is now approved in PD-L1-positive patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Since real-world data are pending, our goal was to evaluate the efficacy and safety of immune checkpoint inhibitor (CPI) therapy in an unselected cohort of patients with SCCHN.
Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2. In August 2016, the US FDA approved the use of pembrolizumab in R/M HNSCC following disease progression on or after platinum-containing chemotherapy. This review highlights the pharmacology, therapeutic efficacy and tolerability data relevant to the use of pembrolizumab for the treatment of R/M HNSCC. Readers will gain greater insight into the HNSCC tumor microenvironment, available biomarkers, and learn about important clinical considerations associated with the use of pembrolizumab and similar immune checkpoint inhibitors.
Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. [2019]There are few effective treatment options for patients with recurrent or metastatic head-and-neck squamous cell carcinoma. Pembrolizumab showed antitumour activity and manageable toxicity in early-phase trials. We aimed to compare the efficacy and safety of pembrolizumab versus standard-of-care therapy for the treatment of head-and-neck squamous cell carcinoma.
Induction chemotherapy combined with immunotherapy in locally advanced head and neck squamous cell carcinoma. [2021]This study aimed to explore the efficacy and safety of sintilimab combined with induction chemotherapy (IC) in locally advanced head and neck squamous cell carcinoma (HNSCC) patients.
Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer. [2023]For patients with metastatic head and neck squamous cell cancer (HNSCC), the outcomes of pembrolizumab in combination with a platinum agent and taxane as first-line therapy remain unknown. The purpose of this study is to characterize the impact of substituting the 5-fluorouracil (5-FU) backbone for a taxane in this chemoimmunotherapy regimen on safety/tolerability and survival outcomes.
Biologics in allergic rhinitis. [2023]This paper aims to review biologics in allergic rhinitis (AR). Biologic agents of Omalizumab, Dupilumab, Mepolizumab, Reslizumab, and Benralizumab are reviewed in detail. The search is performed in "Pubmed," "Google," Google Scholar" and EBSCO Academic Search Ultimate (EKUAL) database of Kırıkkale University Library from 2021 to 2000, and randomized and/or placebo-controlled studies, review papers, meta-analysis, and reports are taken into consideration. The search was performed with the keywords of "allergic rhinitis," "biologics," "biologic agents," "Omalizumab," "Dupilumab," "Mepolizumab," "Reslizumab," "Benralizumab," "Anti IgE," "Anti-IL-4/IL-13", "Anti IL-5". Search is also performed in the "U.S. Food and Drug Administration" (FDA) and "European Medicines Agency" (EMA) web systems. Biological agents such as monoclonal antibodies (MAb) in treatment are called biological therapy or biotherapy. Omalizumab is a humanized Anti-IgE monoclonal antibody. Omalizumab treatment improved the Daily Nasal Rescue Medication Score (DNSSS) and decreased the use of antiallergic drugs in seasonal and perennial AR and rhino-conjunctivitis. Omalizumab is also used in specific immunotherapy patients with allergic rhinitis and reduced allergic reactions associated with allergen immunotherapy, such as anaphylaxis. Dupilumab is an Anti-IL-4/IL-13 biologic agent. Dupilumab treatment significantly improved sino-nasal Outcome Test (SNOT-22) total scores in perennial allergic rhinitis. Anti-IL-5 monoclonal antibodies of Mepolizumab, Reslizumab Benralizumab reduce the number of eosinophils in the blood and tissue, corticosteroid addiction and asthma attacks are reduced, and their use in the treatment of severe eosinophilic asthma has been approved. Biologics, especially Omalizumab, and Dupilumab, may be used more in allergic rhinitis.
Efficacy and Safety of Ragweed SLIT-Tablet in Children with Allergic Rhinoconjunctivitis in a Randomized, Placebo-Controlled Trial. [2021]Ragweed sublingual immunotherapy (SLIT) tablet reduces symptoms and symptom-relieving medication use in adults with allergic rhinitis with or without conjunctivitis (AR/C) but has not been evaluated in children.
Experience with monoclonal antibodies in allergic mediated disease: seasonal allergic rhinitis. [2019]Current therapies for the treatment of seasonal allergic rhinitis include allergen avoidance; pharmacologic interventions such as sympathomimetics, topical and systemic cortico-steroids, and chromones; and immunotherapy. In an attempt to create a novel therapy, therapeutic agents have been designed to inhibit IgE responses that are intimately involved in the induction of the allergic response. Omalizumab, a humanized monoclonal antibody against IgE, represents a novel therapeutic intervention for seasonal allergic rhinitis. Complex formation of omalizumab with serum-free IgE reduces the amount of IgE available for binding to effector cells and thus has the potential to reduce IgE-mediated allergic symptoms. Clinical trial results confirmed that omalizumab reduces free IgE to a level that is associated with suppressed allergic symptoms, reduces concomitant rescue medication use, and improves rhinitis-specific quality of life. Patients treated with omalizumab during one pollen season can be re-treated during the subsequent season with minimal risk of adverse events. Omalizumab is non-allergen-specific and does not induce acute anaphylaxis because of the lack of IgE crosslinking with basophil- or mast-cell-bound IgE. Furthermore, subcutaneous or intravenous administration of omalizumab does not invoke the generation of anti-omalizumab antibodies. Thus, omalizumab represents a novel agent that should assist in the treatment of allergic rhinitis.
Targeting immunoglobulin E as a novel treatment for asthma. [2022]Omalizumab is a recently developed monoclonal anti-IgE antibody. Clinical trials have demonstrated its efficacy in patients with moderate-to-severe and severe or poorly controlled allergic asthma, in patients with seasonal and perennial allergic disease, and in subjects with concomitant asthma and allergic rhinitis. Patients with more severe asthma appear to obtain the greatest benefit from omalizumab therapy. Omalizumab is well tolerated and has a good safety profile. Anti-inflammatory activity has been shown in both allergic asthma and allergic rhinitis. These results confirm the importance of IgE in allergic disease and support the rationale behind the development of a therapeutic anti-IgE antibody. Omalizumab is a significant addition to current asthma treatments and shows great promise as a therapy for allergic rhinitis, in particular for those patients with concomitant allergic disease.
Anti-IgE: A treatment option in allergic rhinitis? [2021]Allergic rhinitis (AR) is the most common IgE-mediated allergic disease. Multiple clinical trials have demonstrated promising results on the AR treatment with biologics, in particular with the use of omalizumab - an anti-IgE antibody. Omalizumab has also been established in the routine management of allergic asthma and chronic idiopathic urticaria. However, currently there is no approved license for the use of biologics in AR in Germany.