Chemotherapy + Immunotherapy for Laryngeal Cancer

Overseen By Renata Ferrarotto

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Pregnancy, Immunodeficiency, Active infection, 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: 14

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy and immunotherapy drugs to evaluate their effectiveness in treating stage II-III laryngeal cancer. The chemotherapy drugs, cisplatin and docetaxel, aim to stop cancer cells from growing or spreading, while the immunotherapy drug, pembrolizumab, helps the immune system attack the cancer. The trial seeks participants newly diagnosed with stage II-III laryngeal cancer who have not yet received treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or immunosuppressive therapy, you may need to adjust your treatment, as these are generally not allowed within 7 days prior to the first dose of the study drug.

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

Research shows that combining cisplatin, docetaxel, and pembrolizumab may help treat laryngeal cancer. Earlier studies found that patients experienced some side effects, but these were mostly manageable. Common side effects included fatigue, nausea, and low blood counts, while serious side effects were less common.

Cisplatin and docetaxel are chemotherapy drugs already used for various cancers. Pembrolizumab is an immunotherapy drug that helps the immune system fight cancer. This combination aims to stop cancer cells from growing and spreading.

Currently tested in a Phase 2 trial, researchers are still assessing its safety. This phase indicates that the treatment has shown some safety in earlier studies but requires further testing. Overall, while side effects are possible, past research considers the treatment fairly well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cisplatin, docetaxel, and pembrolizumab for laryngeal cancer because it integrates chemotherapy with immunotherapy. While traditional treatments often rely solely on chemotherapy or radiation, this approach adds pembrolizumab, an immunotherapy drug that helps the immune system recognize and attack cancer cells. Pembrolizumab targets the PD-1 pathway, which is crucial in preventing the immune system from attacking tumors. This combined strategy not only aims to shrink tumors but also to enhance the body's natural defenses against cancer, offering a potentially more effective and enduring response compared to conventional treatments.

What evidence suggests that this trial's treatments could be effective for laryngeal cancer?

Research has shown that a combination of three drugs—cisplatin, docetaxel, and pembrolizumab—may effectively treat stage II-III laryngeal cancer. This trial will administer this combination to participants to assess its effectiveness. These drugs work together to attack cancer cells, stopping their growth and spread. Studies have found that pembrolizumab, which boosts the immune system, may help the body target cancer more effectively. Some patients have responded well to this treatment, with a few experiencing complete remission, where cancer signs disappeared. This drug combination holds promise for preserving the larynx, potentially maintaining voice function. ^{1 3 4 6 7}

Who Is on the Research Team?

Renata Ferrarotto

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, untreated stage II-III laryngeal squamous cell carcinoma. Participants must be able to use contraception and not be pregnant or breastfeeding. They should have a good performance status (able to carry out daily activities), adequate organ function, and no recent history of other cancer treatments or certain infections like hepatitis B/C or HIV.

Inclusion Criteria

My liver function tests are within the required range.

I have been newly diagnosed with stage II to III larynx cancer and have not received any treatment.

I have provided a recent or archived sample of my tumor for testing.

Exclusion Criteria

I am currently on IV antibiotics for an infection.

I have not received a live vaccine in the last 30 days.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cisplatin, docetaxel, and pembrolizumab every 21 days for up to 4 cycles

12 weeks

4 visits (in-person)

Extension Treatment

Participants who completely respond to the study drugs receive pembrolizumab for 4 additional cycles

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 2 years

Every 6-12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Docetaxel
• Pembrolizumab

Trial Overview The study tests the effectiveness of combining chemotherapy drugs cisplatin and docetaxel with an immunotherapy drug called pembrolizumab in treating laryngeal cancer. The goal is to see if this combination helps control the disease by killing tumor cells and boosting the immune system's response.

How Is the Trial Designed?

Group I: Treatment (cisplatin, docetaxel, pembrolizumab) Experimental Treatment 4 Interventions

Patients receive cisplatin IV over 1 hour, docetaxel IV over 1 hour (patients who develop significant adverse events to cisplatin treatment may receive carboplatin IV over 1 hour instead), and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who completely respond to the study drugs (the disease appears to go away) then receive pembrolizumab IV over 30 minutes on day 1 for 4 additional cycles in the absence of disease progression or unacceptable toxicity.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase I/II trial involving 22 patients with recurrent/metastatic head and neck cancer, the combination of docetaxel and pembrolizumab showed a 22.7% overall response rate, indicating potential efficacy in this difficult-to-treat population.

The treatment was associated with manageable side effects, with myelosuppression being the most common adverse event, while serious immune-related side effects were relatively rare, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. Fuereder, T., Minichsdorfer, C., Mittlboeck, M., et al.[2023]

The combination of docetaxel and cisplatin demonstrated a significant overall response rate of 53.7% in patients with locally advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, indicating its efficacy as a treatment option.

Despite common hematologic and non-hematologic toxicities, the treatment was generally well-tolerated, with serious adverse effects being infrequent due to the use of corticosteroid prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. Schöffski, P., Catimel, G., Planting, AS., et al.[2020]

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]

Docetaxel shows promising efficacy as a treatment for recurrent squamous cell cancer of the head and neck, with response rates between 33% to 44% when combined with cisplatin, and median survival times of 9.6 to 11 months.

In the neoadjuvant setting, docetaxel has demonstrated response rates greater than 90%, indicating its potential for improving disease-free and overall survival, with ongoing trials comparing its effectiveness to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of docetaxel in the management of squamous cell cancer of the head and neck. Glisson, BS.[2018]

Docetaxel is an effective chemotherapy drug that works by binding to microtubules, leading to cell-cycle arrest and apoptosis, and is approved for various cancers including breast, lung, prostate, and recently advanced gastric cancer.

While docetaxel can cause severe neutropenia as a major side effect, alternative dosing schedules have been developed to reduce this toxicity, making it safer for patients with compromised bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. Ramaswamy, B., Puhalla, S.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04030455?term=AREA%5BConditionSearch%5D(%22Laryngeal%20Squamous%20Cell%20Carcinoma%22)%20AND%20AREA%5BInterventionSearch%5D(%22Pembrolizumab%22)&rank=3

Cisplatin, Docetaxel, and Pembrolizumab in Treating ... This phase II trial studies how well cisplatin, docetaxel, and pembrolizumab work in treating patients with stage II-III laryngeal cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11374655/

The European Larynx Organ Preservation Study [MK-3475-C44] In addition, the as-yet untested combination of pembrolizumab with docetaxel and cisplatin may cause additional adverse effects that have not ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.6008

Immuno-chemotherapy as single treatment modality for ... We hypothesized that pembrolizumab (P), cisplatin (C), and docetaxel (D) will cure a subset of LC pts and preserve larynx function.

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-advanced-laryngeal-and-hypopharyngeal-cancer-comparing-docetaxel-cisplatin-and-pembrolizumab-for-patients-eligible-for-laryngectomy/

Study on Advanced Laryngeal and Hypopharyngeal Cancer This study investigates the efficacy of Pembrolizumab, in combination with Docetaxel and Cisplatin, in treating advanced Laryngeal and ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-02750

Cisplatin, Docetaxel, and Pembrolizumab in Treating ... This phase II trial studies how well cisplatin, docetaxel, and pembrolizumab work in treating patients with stage II-III laryngeal cancer.

6. clinicaltrial.be clinicaltrial.be/en/details/62414?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_eligible=0&only_active=0

Cisplatin, Docetaxel, and Pembrolizumab in Treating Patie... 1. Incidence of adverse events. Toxicity data will be summarized by frequency tables. · 2. Laryngeal preservation rate · 3. Relapse-free survival · 4. Overall ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9008154/

A phase I/II trial of concurrent immunotherapy with ... Cisplatin‐based chemoradiation is an established organ‐preserving strategy for locally advanced laryngeal cancer, but long‐term survival remains ...