Pembrolizumab + Radiation vs Chemotherapy + Radiation for Head and Neck Cancer
Recruiting in Palo Alto (17 mi)
+143 other locations
Overseen ByDan P Zandberg
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Immunosuppressants, Live vaccines
Disqualifiers: Active infection, Heart failure, Autoimmune, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial studies the effect of pembrolizumab alone compared to the usual approach (chemotherapy \[cisplatin and carboplatin\] plus radiation therapy) after surgery in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or patients with a second head and neck cancer that is not from metastasis (primary). Radiation therapy uses high energy radiation or protons to kill tumor cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Carboplatin is also in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab alone after surgery may work better than the usual approach in shrinking recurrent or primary head and neck squamous cell carcinoma.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you must not be on immunosuppressive medication within 7 days before starting the trial, except for certain types like low-dose steroids or specific premedications.
What data supports the effectiveness of the drug pembrolizumab when used with radiation for head and neck cancer?
Research shows that pembrolizumab, when combined with radiation, can stimulate the immune system to fight head and neck cancer. It has been effective in treating recurrent or metastatic head and neck cancer and is being studied for use in locally advanced cases, showing promise in early trials.
12345Is the combination of pembrolizumab and radiation safe for head and neck cancer patients?
Pembrolizumab, when used with radiation or chemotherapy, has been generally considered safe for head and neck cancer patients, though it can cause serious side effects like pneumonia, liver inflammation, and thyroid issues. In studies, most patients experienced mild side effects, but some had more severe reactions like anemia and high blood pressure.
15678What makes the drug pembrolizumab unique for head and neck cancer treatment?
Pembrolizumab is unique because it is an immune checkpoint inhibitor that helps the body's immune system attack cancer cells by blocking the PD-1 pathway, and it is being studied in combination with radiation and chemotherapy for locally advanced head and neck cancer, offering a potential alternative for patients who cannot tolerate cisplatin.
12459Eligibility Criteria
Adults aged 18-79 with recurrent or second primary head and neck squamous cell carcinoma, who've had surgery and prior radiation, can join this trial. They must have no distant disease spread, a specific protein (PD-L1) score >=1, and proper organ function. Those with severe allergies to pembrolizumab, active infections requiring systemic treatment, recent live vaccines, certain heart conditions or transplants are excluded.Inclusion Criteria
I haven't had any live vaccines in the last 30 days.
My tumor area previously received high-dose radiation.
I haven't needed steroids for lung inflammation in the last 3 years.
I am between 18 and 79 years old.
My cancer has spread beyond the original tumor site.
My cancer cells are found right at or very close to the edge of the removed tissue.
My cancer has returned in the head or neck area where I was previously treated with radiation.
My recent scans show no signs of cancer spread.
My heart is healthy enough for treatment, not classified as NYHA class III or IV.
My tumor's PD-L1 score is 1 or higher, tested in a certified lab.
I am fully active or can carry out light work.
I do not have an infection that needs treatment through my body.
Exclusion Criteria
I do not have hepatitis B or active hepatitis C.
Participant Groups
The trial is testing the effectiveness of pembrolizumab alone versus the usual treatment of chemotherapy combined with radiation after surgery for patients with head and neck cancer that has returned. Pembrolizumab is an immunotherapy drug designed to boost the body's immune response against cancer cells.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm C (pembrolizumab)Experimental Treatment3 Interventions
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout the trial.
Group II: Arm B (cisplatin, carboplatin, IMRT, PBRT)Active Control6 Interventions
Patients receive cisplatin or carboplatin IV on day 1. Treatment repeats every 7 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo IMRT or PBRT QD for a total of 30 fractions in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout the trial.
Carboplatin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
🇪🇺 Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Smilow Cancer Hospital Care Center - WaterfordWaterford, CT
Siteman Cancer Center at West County HospitalCreve Coeur, MO
Dayton Physicians LLC-Miami Valley SouthCenterville, OH
Cleveland Clinic FoundationCleveland, OH
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [2023]Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti-PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC.
Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. [2021]Current treatment guidelines for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) recommend multimodal treatment, including chemoradiation therapy (CRT) or surgery followed by radiation, with or without chemotherapy. The immune checkpoint inhibitor pembrolizumab has previously demonstrated antitumor activity in recurrent and/or metastatic HNSCC in large Phase III trials. For patients with locally advanced disease, Phase Ib data on the use of pembrolizumab in combination with chemoradiation have shown the approach to be safe and feasible. We describe here the design and rationale for KEYNOTE-412, a randomized, double-blind, Phase III trial investigating pembrolizumab or placebo administered concurrently with CRT and as maintenance treatment in patients with locally advanced HNSCC. Clinical Trial Registration: NCT03040999 (ClinicalTrials.gov).
Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. [2022]Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS).
Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. [2022]Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC.
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.
Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. [2023]Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities.
FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. [2019]On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Approval was based on the objective response rate (ORR) and duration of response (DoR) in a cohort of patients in a nonrandomized multi-cohort trial (KEYNOTE-012) that included 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. Patients received either intravenous pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks. ORR was determined by independent review according to Response Evaluation Criteria in Solid Tumors 1.1. ORR was 16% (95% confidence interval 11, 22) with a complete response rate of 5%. DoR ranged from 2.4+ months to 27.7+ months. Twenty-three of 28 responding patients (82%) had response durations of ≥6 months. Safety was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab. Frequent (≥2%) serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders. The benefit-risk profile of pembrolizumab was considered acceptable in this patient population. As a condition of accelerated approval, Merck is required to conduct a confirmatory trial; this trial, KEYNOTE-040, is ongoing.
Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. [2023]Novel chemo-immunotherapy (chemo-IO) combinations should be evaluated, which may be suitable for cisplatin-unfit or fluoropyrimide-ineligible patients with recurrent or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) to guarantee higher and deeper responses than IO alone. The aim of the present study was to review our experience using pembrolizumab-carboplatin-paclitaxel (pembro + CP) in patients with R/M SCCHN. This was a retrospective study of patients with R/M SCCHN who received pembro + CP in any-line via a compassionate-use program. The present study evaluated safety using Common Terminology Criteria for Adverse Events v4.0, compliance, overall response rate (ORR) and disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors 1.1, duration of treatment, progression-free survival (PFS) and overall survival (OS). Between March 2020 and August 2021, 10 patients were identified (median age, 64 years; female, 60%; Eastern Cooperative Oncology Group 2, 80%). A total of 8 patients received pembro + 3-weekly carboplatin-paclitaxel (3wkCP). A total of 2 patients received pembro + weekly carboplatin-paclitaxel (wkCP). Patients received a median of 3 lines (range, 0-6) of systemic therapy prior to pembro + CP and 80% received IO in previous lines. Grade 1-2 adverse events (AEs) occurred in 100% of patients. Grade 3-5 AEs occurred in 30% of patients [all grade 3 (anemia, neutropenia, thrombopenia, hypertension)]. The mean numbers of pembro + wkCP and pembro + 3wkCP cycles were 2.5 and 6. The ORR (n=7) was 14% (1/7) with one complete response. The DCR was 43% (3/7). The median PFS (n=7) and OS (n=10) times since pembro + CP were 5 months (95% CI, 1-9) and 6 months (95% CI, 0.5-14), respectively. In this small retrospective series of heavily pretreated patients, pembro + CP was well tolerated, and compliance was high. Studies should be conducted to prospectively evaluate the safety and efficacy of this combination in patients with R/M SCCHN.
Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. [2023]To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN).