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

Trial Summary

What is the purpose of this trial?

To find out if adding medication can help treat or prevent lymphedema and/or fibrosis related to radiation therapy, in survivors of head and neck cancer. Researchers will compare these drugs to find the most effective therapy for preventing or limiting these side effects.

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.

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

Research suggests that statins, like Pravastatin, may help reduce treatment toxicity and improve outcomes in head and neck cancer. Additionally, statins and anti-inflammatory drugs have shown potential cancer-protective effects, which could support their use in this drug therapy. ^{1 2 3 4 5}

Is pentoxifylline safe for use in humans?

Pentoxifylline has been used in patients with radiation-related soft tissue injuries, and it appears to help heal these injuries and reduce pain. It was generally well-tolerated in the study, suggesting it is safe for human use in this context. ^{4 6 7 8 9}

How does the drug therapy for head and neck cancer using Ketoprofen, Pentoxifylline, Pirfenidone, and Pravastatin differ from other treatments?

This drug therapy is unique because it combines Ketoprofen, Pentoxifylline, Pirfenidone, and Pravastatin, which are not traditionally used together for head and neck cancer. Pravastatin, a statin drug, is being repurposed for its potential to reduce toxicity and improve survival outcomes, which is a novel approach compared to standard chemotherapy agents like cisplatin and taxanes. ^{2 10 11 12 13}

Research Team

Clifton Fuller, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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 do not have severe liver disease, cirrhosis, or active alcoholism.

I have had a heart attack or severe heart disease.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Pravastatin Reverses Established Radiation-Induced Cutaneous and Subcutaneous Fibrosis in Patients With Head and Neck Cancer: Results of the Biology-Driven Phase 2 Clinical Trial Pravacur. [2019]

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

Repurposing Statin Drugs to Decrease Toxicity and Improve Survival Outcomes in Head and Neck Cancer. [2022]

3. United States 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. [2020]

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

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

5. Greece pubmed.ncbi.nlm.nih.gov

Additive antitumor effects of celecoxib and simvastatin on head and neck squamous cell carcinoma in vitro. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients. [2021]

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

Pentoxifylline in the treatment of radiation-related soft tissue injury: preliminary observations. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Radiochemotherapy with amifostine cytoprotection for head and neck cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

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

Chemotherapy in head and neck cancer. Overview of newer agents. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Oral chemotherapy in head and neck cancer. [2018]

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

Biweekly paclitaxel, cisplatin, tegafur, and leucovorin as neoadjuvant chemotherapy for unresectable squamous cell carcinoma of the head and neck. [2015]

13. England pubmed.ncbi.nlm.nih.gov

New approaches to enhance chemotherapy in SCCHN. [2020]