Methylnaltrexone for Head and Neck Cancer

Overseen By Juan Cata, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Opioid antagonists

Disqualifiers: Non-English/Spanish, Uncontrolled illness, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests methylnaltrexone to determine its safety for individuals with oral cavity squamous cell carcinoma, a type of head and neck cancer, before surgery. The goal is to assess whether patients can safely take this medication for two weeks leading up to their surgery. Individuals diagnosed with this specific cancer type and planning surgery might be suitable candidates for the trial. Participants must self-administer the injection under the skin in their abdominal area during this period. As a Phase 4 trial, this research aims to understand how this already FDA-approved and effective treatment benefits more patients.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot use other opioid antagonists during the study. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

What is the safety track record for methylnaltrexone?

Research has shown that methylnaltrexone has undergone thorough safety testing in people. The FDA has approved it to treat constipation caused by opioid use in individuals with serious illnesses. Studies have found that methylnaltrexone is generally well-tolerated, with most side effects being mild, such as stomach pain or nausea. These studies have not linked methylnaltrexone to serious side effects.

Since this study is in a late phase, methylnaltrexone has already undergone extensive testing in earlier trials, supporting its safety. This study specifically examines its use in patients with head and neck cancer to ensure it remains safe in this new context. Overall, existing research suggests methylnaltrexone is safe for use in people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Methylnaltrexone is unique because it offers a new approach for managing complications in head and neck cancer, specifically targeting opioid-induced constipation. While traditional treatments for this condition often involve dietary changes, laxatives, or stool softeners, methylnaltrexone works by blocking the effects of opioids on the gut without affecting pain relief. This mechanism allows patients to manage their symptoms more effectively without compromising their pain management. Researchers are excited about methylnaltrexone because it provides a targeted solution that could improve the quality of life for patients undergoing cancer treatment.

What is the effectiveness track record for methylnaltrexone in treating head and neck cancer?

Research has shown that methylnaltrexone, which participants in this trial will receive, may help reduce tumor growth in head and neck cancers, as well as in other cancers like melanoma and breast cancer, based on animal studies. Methylnaltrexone is already approved and effectively treats constipation caused by opioid painkillers, indicating its safety for humans. While primarily used for this purpose, its potential to slow cancer growth is promising. Ongoing studies aim to confirm this effect in people with specific cancers, such as oral cavity squamous cell carcinoma. ^{1 2 4 5 6}

Who Is on the Research Team?

Juan Cata, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with confirmed oral cavity squamous cell carcinoma that can be surgically removed. Participants must be able to take methylnaltrexone for two weeks before surgery, follow the study plan, and use approved birth control. Excluded are those on other trials, with allergies to similar drugs, uncontrolled illnesses like kidney or liver disease, HIV patients not on effective therapy, mental/social issues affecting compliance, urgent surgeries needed, metastatic disease or brain tumors present.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

My oral cancer is confirmed and can be treated with surgery aimed at curing it.

I can take the study medication for at least two weeks before surgery.

Exclusion Criteria

I need surgery urgently or as an emergency.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to methylnaltrexone or other agents used in the study

I do not speak English or Spanish.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive methylnaltrexone for 2 weeks before surgery

2 weeks

Participants are instructed on self-administration of injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Methylnaltrexone

Trial Overview The MINK study tests if it's safe to give methylnaltrexone to patients with head and neck cancer for two weeks before their surgery. The goal is to see how well they tolerate the drug in this short period.

How Is the Trial Designed?

Group I: Methylnaltrexone Experimental Treatment 1 Intervention

Participants will be given 14 pre-filled syringes of methylnaltrexone. Participants will be instructed how to take the drug as an injection under the skin of your abdominal area.

Methylnaltrexone is already approved in United States, European Union for the following indications:

Approved in United States as Relistor for:

• Opioid-induced constipation in adult patients with chronic non-cancer pain

Approved in European Union as Relistor for:

• Opioid-induced constipation in adult patients with chronic non-cancer pain

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

The EXTREME regimen, which combines cetuximab with platinum and 5-fluorouracil, remains the standard treatment for previously untreated patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

Nivolumab, an anti-PD-1 monoclonal antibody, is now considered the standard of care for patients with R/M HNSCC who have progressed after platinum-based therapy, showing a survival benefit over other treatments in the CheckMate 141 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing treatments for recurrent or metastatic head and neck squamous cell carcinoma. Specenier, P., Vermorken, JB.[2019]

The EXTREME regimen, which combines cetuximab with cisplatin and 5-fluorouracil, has significantly improved overall response rates and survival outcomes for patients with recurrent/metastatic head and neck cancer, making it the standard first-line treatment.

Recent advancements in treatment options, particularly immune checkpoint inhibitors like nivolumab and pembrolizumab, have shown promising results in extending overall survival for patients in later treatment lines, with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy and immunotherapy for recurrent and metastatic head and neck cancer: a systematic review. Guidi, A., Codecà, C., Ferrari, D.[2022]

Cytotoxic chemotherapy for recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC) primarily includes platinum agents, taxanes, and antimetabolic agents, which are commonly used to manage the disease.

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, shows modest effectiveness in treating R/M HNSCC, highlighting the importance of a multidisciplinary approach in palliative care planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current recommendations for systemic therapy of recurrent and/or metastatic head and neck squamous cell cancer. Fury, MG., Pfister, DG.[2019]

In patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC), treatment options have evolved but survival rates remain largely unchanged, highlighting the need to balance treatment efficacy with patient quality of life.

For patients with high PD-L1 expression (CPS ≥ 20), pembrolizumab is recommended, while those with lower expression may benefit from combinations like pembrolizumab with cisplatin and 5FU, or the EXTREME regimen, which includes cetuximab, depending on affordability and support availability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative chemotherapy in head and neck cancer: balancing between beneficial and adverse effects. Rajendra, A., Noronha, V., Joshi, A., et al.[2021]

In a phase II trial involving 32 patients with recurrent or metastatic squamous carcinoma of the head and neck, topotecan was administered but failed to show any responses in either chemonaive or previously treated patients.

The treatment resulted in significant side effects, including grade III/IV neutropenia in 16% and anemia in 18% of patients, and the median survival was only 4.6 months for chemonaive patients and 3.2 months for those previously treated, indicating a lack of efficacy and prompting the decision not to pursue further evaluation of topotecan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of efficacy of topotecan in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: an Eastern Cooperative Oncology Group Trial (E3393). Murphy, BA., Leong, T., Burkey, B., et al.[2019]

Citations

1. ir.bauschhealth.com ir.bauschhealth.com/news-releases/2024/03-06-2024

Salix Pharmaceuticals Announces a Phase 2 Investigator ... The trial is designed to evaluate the potential of treating oral cavity squamous cell carcinoma patients with MNTX.

2. cancernetwork.com cancernetwork.com/view/phase-iii-trial-demonstrates-efficacy-methylnaltrexone-use-advanced-illness-patients-opioid-induced

Phase III Trial Demonstrates Efficacy of Methylnaltrexone ... The data published in NEJM are particularly exciting because not only do they demonstrate that Relistor has the potential to relieve OIC effectively, but that ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000MedR.pdf

208271Orig1s000 - accessdata.fda.gov It is the opinion of this reviewer that methylnaltrexone bromide tablets 450 mg may be approved for marketing in the United States for the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6267944/

Treatment with methylnaltrexone is associated ... In clinically relevant doses, MOR antagonists reduced tumor growth in NSCLC, head and neck cancer, melanoma and breast cancer in vivo models [11, 16–18].

5. synapse.patsnap.com synapse.patsnap.com/article/phase-2-study-of-relistor-for-treatable-head-and-neck-cancer

Phase 2 Study of RELISTOR for Treatable Head and Neck ... This study is a prospective pilot study where patients receive subcutaneous MNTX both before and after surgery. The Senior Vice President of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3046621/

Utilization of Methylnaltrexone (Relistor) For Opioid- ... Methylnaltrexone bromide (Relistor, Pfizer) received FDA approval for the treatment of opioid-induced constipation in April 2008 based on two randomized, ...