Chemotherapy + Immunotherapy for Laryngeal Cancer

Recruiting in Houston (>99 mi)

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

27 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drugs used in the Chemotherapy + Immunotherapy for Laryngeal Cancer trial?

Research shows that the combination of docetaxel and cisplatin is effective in treating head and neck cancers, with response rates of 33% to 44% in recurrent cases and over 90% in initial treatments. These drugs are known to be active against squamous cell carcinoma, which is similar to laryngeal cancer. ^{1 2 3 4 5}

Is the combination of chemotherapy and immunotherapy safe for humans?

Research shows that combinations of chemotherapy drugs like cisplatin and docetaxel with immunotherapy drugs like pembrolizumab have been studied for safety in various cancers. Common side effects include mild to moderate issues like anemia (low red blood cells) and neutropenia (low white blood cells), but severe side effects are less common. Overall, these combinations are generally considered safe for human use, though individual experiences may vary. ^{3 6 7 8 9}

What makes the chemotherapy and immunotherapy drug combination for laryngeal cancer unique?

This treatment combines chemotherapy drugs cisplatin and docetaxel with the immunotherapy drug pembrolizumab, which may enhance the body's immune response against cancer cells, potentially offering a more effective approach than chemotherapy alone. ^{2 3 4 10 11}

What is the purpose of this trial?

This phase II trial studies how well cisplatin, docetaxel, and pembrolizumab work in treating patients with stage II-III laryngeal cancer. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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 cisplatin, docetaxel, and pembrolizumab may help to control the disease.

Research Team

Renata Ferrarotto

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. England 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. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Randomized trial of laryngeal organ preservation evaluating two cycles of induction chemotherapy with platinum, docetaxel, and a novel Bcl-xL inhibitor. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Sequential four-drug chemotherapy and intensity-modulated radiotherapy for larynx preservation in resectable advanced larynx and hypopharynx cancer: A pilot study. [2017]

6. Greece 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study. [2023]

8. Spain pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. [2018]

9. China pubmed.ncbi.nlm.nih.gov

[Clinical observation of TP regiment for treating refractory and terminal squamous cancer of the esophagus]. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. [2022]