Pembrolizumab + Radiation vs Chemotherapy + Radiation for Head and Neck Cancer

Recruiting at 174 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Active infection, Heart failure, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 39

Duration: 12 months

188 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether pembrolizumab alone is more effective than the usual chemotherapy combined with radiation after surgery for treating head and neck cancer that has returned or is a new occurrence. Pembrolizumab, an immunotherapy, may help the immune system fight cancer more effectively, while the standard approach uses chemotherapy drugs like cisplatin and carboplatin to kill cancer cells. Individuals who have undergone head and neck cancer surgery and radiation treatment before, and have specific tumor features, might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that patients usually tolerate pembrolizumab well. Studies have found that most side effects are manageable, though serious side effects can occur but are uncommon. For example, some people might feel tired or nauseous, but these symptoms are usually mild.

Cisplatin and carboplatin, chemotherapy drugs, have known side effects. They can cause nausea, vomiting, and lower white blood cell counts, increasing the risk of infection. Carboplatin may be gentler on the body than cisplatin, potentially causing fewer or less severe side effects.

Overall, these treatments have been used in many patients and are considered safe, but individual experiences can vary. Patients should always discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they offer new ways to tackle the disease. Pembrolizumab is a game-changer as it is an immunotherapy drug that helps the body's immune system target and destroy cancer cells, unlike traditional chemotherapy drugs like cisplatin and carboplatin, which directly attack cancer cells. This approach can potentially lead to fewer side effects and longer-lasting effects. Moreover, pembrolizumab is given less frequently, every six weeks, compared to the weekly schedule of chemotherapy, making it more convenient for patients. These innovations could offer new hope for better outcomes and improved quality of life for patients.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

This trial will compare two treatment approaches for head and neck cancer: pembrolizumab combined with radiation and chemotherapy combined with radiation. Research has shown that pembrolizumab, which participants in this trial may receive, can improve survival rates in patients with head and neck cancer by activating the immune system. In contrast, chemotherapy with drugs like cisplatin and carboplatin, part of another treatment arm in this trial, is a well-known approach that stops or slows the growth of cancer cells. Both treatments have effectively managed head and neck cancer, but they work in different ways. ^{1 5 6 7 8}

Who Is on the Research Team?

Dan P Zandberg

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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.

I haven't taken strong immune-suppressing drugs in the last week, except for low-dose or topical steroids.

My tumor area previously received high-dose radiation.

Exclusion Criteria

I do not have hepatitis B or active hepatitis C.

NOTE: No testing for hepatitis B and hepatitis C is required unless mandated by a local health authority

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either pembrolizumab or chemotherapy with radiation therapy

12 months

Pembrolizumab: 9 visits (every 6 weeks); Chemotherapy: 6 visits (weekly) with daily radiation

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up at 30 days post-treatment, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Pembrolizumab
• Proton Beam Radiation Therapy

Trial Overview 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.

How Is the Trial Designed?

Group I: Arm C (pembrolizumab) Experimental Treatment 3 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 Control 6 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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., et al.[2023]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

In a study of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

In a phase III trial involving 891 patients with stage III or IV head and neck carcinoma, adding cetuximab to the radiation-cisplatin treatment did not improve progression-free survival (PFS) or overall survival (OS) compared to radiation-cisplatin alone.

Patients with p16-positive oropharyngeal carcinoma had significantly better PFS and OS compared to those with p16-negative tumors, indicating that p16 status is a more important factor for outcomes than the addition of cetuximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.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. Ang, KK., Zhang, Q., Rosenthal, DI., et al.[2022]

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Tao, Y., Biau, J., Sun, XS., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694497/

Real-World Evidence on the Effectiveness of Pembrolizumab ... The study showed some beneficial effects of pembrolizumab monotherapy in recurrent/metastatic/unresectable HNSCC patients in real-world scenarios.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2415434

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02508

Updated Results of the Phase III KEYNOTE-048 Study Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS ≥ 1 (HR, 0.64; 95% CI, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02252042

Study Details | NCT02252042 | Pembrolizumab (MK-3475) ... The primary study hypothesis is that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard treatment.

5. merck.com merck.com/news/mercks-keytruda-pembrolizumab-significantly-improved-overall-survival-compared-to-standard-of-care-as-monotherapy-and-in-combination-with-chemotherapy-as-first-line-treatment-for-patients/

Merck's KEYTRUDA (pembrolizumab) Significantly ... “In this study, KEYTRUDA showed the potential to significantly prolong survival when used as first-line therapy for patients whose head and neck cancer had ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02252042?tab=results

Study Results | Pembrolizumab (MK-3475) Versus ... Serious AEs and Other AEs were reported according to treatment course for all randomized participants who received ≥1 dose of study treatment. Per protocol, ...

7. merck.com merck.com/news/keytruda-pembrolizumab-as-perioperative-treatment-with-standard-of-care-soc-adjuvant-therapy-significantly-improved-event-free-survival-compared-to-soc-alone-in-patients-with-resectable-loca/

KEYTRUDA® (pembrolizumab) as Perioperative Treatment ... Results at the first interim analysis of the trial showed KEYTRUDA significantly improved event-free survival (EFS) as part of a perioperative treatment regimen ...

8. clinicaltrialsarena.com clinicaltrialsarena.com/news/msd-keytruda-combo/

MSD reports outcomes from trial of Keytruda combination ... After a median follow-up at 38.3 months, the therapy had decreased the EFS event risk by 34% in subjects whose combined positive score (CPS) was ...