Drug Therapy for Head and Neck Cancer

Overseen By Clifton Fuller, MD

Age: Any Age

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Statins, Xanthine derivatives

Disqualifiers: Liver disease, Myopathy, Coronary disease, Diabetes, 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: Unknown

Duration: 12 months

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding certain medications can prevent or reduce lymphedema (swelling) and fibrosis (tissue thickening) after radiation treatment in head and neck cancer survivors. Researchers are testing four drugs—Ketoprofen, Pentoxifylline, Pirfenidone, and Pravastatin—against a standard care group to identify the best option for avoiding these side effects. The trial seeks participants who have had head and neck cancer, completed radiation with a dose of 30Gy or more, and are experiencing noticeable swelling or thickening more than six months after treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in care.

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, you cannot participate if you are taking investigational agents or have allergies to certain drugs like statins or xanthine derivatives.

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

In a previous study, pravastatin showed promise in reducing side effects from cancer treatments, suggesting it might be safe for patients with head and neck cancer. Studies have also found that pravastatin can help with radiation-induced fibrosis, which involves the thickening and scarring of tissue.

Research has shown that pentoxifylline, when combined with tocopherol (vitamin E), can be used safely. This combination has been found to reduce and even reverse fibrosis caused by radiation. It has been successfully used in patients undergoing dental extractions after head and neck cancer treatments.

Ketoprofen, a type of pain reliever, has been shown to be safe for patients with head and neck cancer and is known to help with pain after cancer-related surgeries.

Pirfenidone has been used to treat lung conditions and has shown safety in various studies. While some reports mention minor issues, no consistent safety concerns have been noted.

Since these drugs are in a Phase 2 trial, they have already demonstrated some level of safety in earlier studies. This phase will further explore their effectiveness and safety in preventing or reducing side effects like swelling (lymphedema) and fibrosis in cancer survivors. ^{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 approaches compared to traditional options like surgery, radiation, and chemotherapy. Ketoprofen, used in one of the study arms, is an anti-inflammatory that might help reduce tumor-associated inflammation, potentially slowing cancer growth. Pravastatin, typically known for lowering cholesterol, may inhibit cancer cell proliferation, which is a different approach from standard chemotherapy. Pentoxifylline combined with Tocopherol (vitamin E) might enhance blood flow and tissue oxygenation, possibly improving the effectiveness of other treatments. Lastly, Pirfenidone, known for treating pulmonary fibrosis, could interfere with cancer cell signaling pathways. These diverse mechanisms offer fresh hope for more effective and targeted cancer therapies.

What evidence suggests that this trial's treatments could be effective for preventing or limiting lymphedema and fibrosis in head and neck cancer survivors?

In this trial, participants will receive one of several treatments for head and neck cancer. Research has shown that pravastatin, which participants may receive, can reduce tissue thickening (fibrosis) in patients treated for head and neck cancer. One study found that after a year, fibrosis thickness decreased by at least 30% in patients taking pravastatin. Another treatment option is the combination of pentoxifylline and tocopherol, proven to lessen and even reverse radiation-induced fibrosis, improving symptoms and healing. Ketoprofen, also studied in this trial, is known for its superior ability to relieve pain in head and neck cancer treatment compared to other pain medications. Lastly, pirfenidone, often used for lung issues, is being tested for its potential to reduce fibrosis and alter the tumor environment, which might help prevent cancer progression. ^{2 6 7 8 9}

Who Is on the Research Team?

Clifton Fuller, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for survivors of head and neck cancers who have developed lymphedema or fibrosis due to radiation therapy. Participants should be experiencing related symptoms like thyroid fibrosis, primary lymphedema, or postprandial fullness syndrome.

Inclusion Criteria

I've had neck radiotherapy with a dose of 30Gy or more.

I had head and neck cancer but am currently free of active disease.

My kidney function is low, with a creatinine clearance under 30 mL/min.

Exclusion Criteria

Contraindications for MRI subject to the discretion of the treating physician and Principal Investigator (PI), as the MRI may be optional

I have had a heart attack or severe heart disease.

I am either pregnant, post-menopausal, or male.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various candidate agents to treat or prevent lymphedema and/or fibrosis related to radiation therapy for 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments at 12 months post-randomization

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ketoprofen
• Pentoxifylline
• Pirfenidone
• Pravastatin

Trial Overview The study tests if Pravastatin, Pentoxifylline, Pirfenidoneone, ketoprofen, tocopherol can improve or prevent radiation-related lymphedema and/or fibrosis compared to Standard of Care (SOC). It's a randomized-controlled trial with adaptive elements.

How Is the Trial Designed?

Group I: Treatment with SoC (Control) Experimental Treatment 1 Intervention

No pharmacologic intervention (control)

Group II: Treatment with Pravastatin QD Experimental Treatment 1 Intervention

40 mg/day for 12 months

Group III: Treatment with Pirfenidone TID Experimental Treatment 1 Intervention

801 mg for 12 months

Group IV: Treatment with Pentoxifylline TID + Tocopherol Experimental Treatment 2 Interventions

400 mg/1000 IU vitamin E for 12 months

Group V: Treatment with Ketoprofen TID Experimental Treatment 1 Intervention

75 mg for 12 months

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

This systematic review and meta-analysis evaluated the protective effects of metformin, statins, and anti-inflammatory drugs on head and neck cancer, highlighting their potential roles in cancer prevention.

The findings suggest that these medications may offer beneficial effects in reducing the risk or severity of head and neck cancer, although specific efficacy details and mechanisms were not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited Evidence Suggests Metformin Might Be Beneficial to Reduce Head and Neck Cancer Risk and Increase Overall Survival, While Any Benefit With Antiinflammatory Drugs Is Inconsistent. Veitz-Keenan, A., Silvestre Calle, TD., Bergamini, M.[2020]

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]

Statin drugs, commonly used for lowering cholesterol, may improve survival rates and reduce treatment-related toxicities in patients with head and neck squamous cell carcinoma (HNSCC), based on a review of preclinical and clinical studies.

Due to their affordability and safety profile, statins are suggested as a promising adjunctive therapy in HNSCC treatment, warranting further research to understand their mechanisms and enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repurposing Statin Drugs to Decrease Toxicity and Improve Survival Outcomes in Head and Neck Cancer. Bourguillon, RO., Stokes, WA., Dorth, J., et al.[2022]

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]

Cisplatin remains the primary chemotherapy agent for treating recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN), often used in combination with 5-FU, while taxanes are being explored for their potential benefits in treatment regimens.

The EGFR-directed monoclonal antibody cetuximab has shown effectiveness in combination with chemotherapy for recurrent/metastatic SCCHN and may also be beneficial as a single agent in platinum-resistant cases, highlighting the potential of targeted therapies in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New approaches to enhance chemotherapy in SCCHN. Bourhis, J.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4907166/

Post-operative pain management in head and neck cancer ... A meta-analysis by Deandrea et al. found that 43% of cancer patients from 26 different studies had insufficient control of pain 19.

2. jbuon.com jbuon.com/archive/13-4-519.pdf

13-4-519.pdf The study included 60 adult patients of both sexes, undergoing operations for cancer of the head and neck who were randomized to either ketoprofen. (n=30) or to ...

3. researchgate.net researchgate.net/publication/23789728_Ketoprofen_is_superior_to_metamizole_in_relieving_postoperative_pain_after_head_and_neck_tumor_operation

Ketoprofen is superior to metamizole in relieving ... We conducted a randomized, single blind study to compare the analgesic efficacy and safety of ketoprofen and dipyrone (metamizole) after major head and neck ...

4. pharmacia.pensoft.net pharmacia.pensoft.net/article/113677/

The effects of meloxicam, lornoxicam, ketoprofen, and ... Some studies revealed a reduced risk of breast, prostate, colorectal, ovarian, and head and neck cancer after NSAIDs therapy, while others ...

5. withpower.com withpower.com/trial/phase-2-fibrosis-8-2025-eb28e

Drug Therapy for Head and Neck Cancer What data supports the effectiveness of the drug therapy for head and neck cancer involving Ketoprofen, Pentoxifylline, Pirfenidone, and Pravastatin?

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5716792/

Nonsteroidal anti-inflammatory drugs using and risk of ... Our results showed statistically significant association between nonsteroidal anti-inflammatory drugs using and head and neck cancer risk reduction.

7. pharmacia.pensoft.net pharmacia.pensoft.net/article/113677/list/18/

The effects of meloxicam, lornoxicam, ketoprofen, and ... Some studies revealed a reduced risk of breast, prostate, colorectal, ovarian, and head and neck cancer after NSAIDs therapy, while others ...

8. sciencedirect.com sciencedirect.com/org/science/article/pii/S0428029624001197

The effects of meloxicam, lornoxicam, ketoprofen, and ... Some studies revealed a reduced risk of breast, prostate, colorectal, ovarian, and head and neck cancer after NSAIDs therapy, while others demonstrated no ...

9. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2767741

NSAID Use and Survival in Patients With Head and Neck ... Concurrent use of NSAIDs has been shown to be associated with a survival advantage for colorectal cancer and a wide range of cancer histologies.