Afatinib + Prednisone for Lung Cancer

Overseen By Ebele Mbanugo

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: EGFR inhibitors, IMIDs, Anti-TNF

Disqualifiers: Symptomatic brain metastases, Uncontrolled 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: 60 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of two drugs, afatinib (Gilotrif) and prednisone, can effectively treat advanced squamous non-small cell lung cancer (NSCLC) that has previously been treated. The trial aims to determine how well these drugs work together in controlling the cancer. It seeks participants who have tried up to three different treatments for their lung cancer and have not used certain other medications. Individuals dealing with this specific type of lung cancer and not on certain steroid medications may be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have had systemic glucocorticoids (a type of steroid) within 3 weeks before starting the study. It's best to discuss your specific medications with the trial team.

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

Research has shown that afatinib has been widely studied for treating non-small cell lung cancer. Past studies found afatinib to be generally safe, with most patients tolerating it well. Common side effects include diarrhea, rash, and mouth sores, but these can usually be managed with proper care.

Prednisone, a steroid, has long been used to treat various conditions by reducing inflammation and managing symptoms. While generally safe, prednisone can cause side effects like increased appetite, mood changes, and trouble sleeping, especially with long-term use.

The combination of afatinib and prednisone for lung cancer is under study to determine if they work better together than alone. Although the safety of this combination is still under review, both drugs have established safety records individually. Participants interested in joining the trial will receive regular monitoring to manage any side effects that might occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Researchers are excited about the combination of Afatinib and Prednisone for treating lung cancer because it offers a novel approach compared to current treatments like chemotherapy and targeted therapies, such as EGFR inhibitors. Afatinib is a type of EGFR inhibitor, but it works differently by irreversibly binding to the EGFR, which may enhance its effectiveness against cancer cells that have become resistant to other EGFR inhibitors. Adding Prednisone, a steroid that can help manage inflammation and improve patient comfort, could potentially enhance the overall treatment response. This combination aims to tackle the cancer more aggressively and improve patient outcomes.

What evidence suggests that the combination of Afatinib and Prednisone could be effective for lung cancer?

Research has shown that afatinib, when used alone, can be effective for certain types of lung cancer, helping patients live longer without their cancer worsening, with an average duration of 19.1 months. In this trial, participants will receive a combination of afatinib and prednisone. Prednisone, a steroid, helps reduce swelling and manage side effects. The combination of afatinib with prednisone aims to combat cancer growth while controlling inflammation. Early results suggest this combination may shrink tumors in patients with squamous non-small cell lung cancer (NSCLC). This approach offers hope for those who have already tried other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Sheena Bhalla

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

Adults over 18 with advanced squamous NSCLC who've had up to three prior treatments can join. They must not have used systemic steroids recently, EGFR inhibitors, IMIDs, or anti-TNF antibodies. Participants need measurable disease per RECIST 1.1 and good organ/marrow function. No pregnant/nursing individuals or those with certain health issues like uncontrolled diabetes or symptomatic brain metastases.

Inclusion Criteria

I have enough tissue samples saved for further study.

Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.

You must have a measurable disease according to specific medical guidelines.

Exclusion Criteria

I have brain metastases that are causing symptoms or need more steroids.

I am allergic to afatinib or prednisone.

Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Afatinib 40 mg PO daily and Prednisone 40 mg PO daily starting 7 days after Afatinib

60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Afatinib
• Prednisone

Trial Overview The trial tests the effectiveness of afatinib combined with prednisone in patients who have previously treated advanced squamous NSCLC. It aims to see if this combination helps control cancer better than previous therapies they've received.

How Is the Trial Designed?

Group I: Afatinib + Prednisone Experimental Treatment 1 Intervention

Afatinib 40 mg PO daily Prednisone 40 mg PO daily starting 7 days after Afatinib

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

Approved in United States as Gilotrif for:

• Non-small cell lung cancer

Approved in European Union as Giotrif for:

• Non-small cell lung cancer

Approved in Canada as Gilotrif for:

• Non-small cell lung cancer

Approved in Japan as Giotrif for:

• Non-small cell lung cancer

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Afatinib is an irreversible inhibitor of the ErbB family of tyrosine kinases, specifically approved for treating advanced non-small-cell lung cancer in adults with EGFR mutations.

Ongoing research is exploring the efficacy of afatinib in treating other types of cancers, such as head and neck squamous cell carcinoma (HNSCC) and breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afatinib. Wecker, H., Waller, CF.[2018]

Cisplatin-based chemotherapy in the 1980s improved median survival for advanced non-small cell lung cancer (NSCLC) patients to about 7 months, compared to 4 months with best supportive care.

Newer drugs like vinorelbine, docetaxel, and gemcitabine have shown even better results, with median survivals over 7 months, and combinations with cisplatin have achieved median survivals of 10 months, suggesting potential for improved outcomes in advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do newer chemotherapeutic agents improve survival in non-small cell lung cancer? Rigas, JR.[2022]

In a phase III trial involving 612 patients with inoperable stage IIIA/B and IV non-small cell lung cancer, the combination of vinorelbine and cisplatin significantly improved survival compared to other regimens, with a one-year survival rate of 38% for the vinorelbine/cisplatin group among patients with better performance status (PS 0-1).

The study found that patients with a performance status of 2 did not benefit from cisplatin, suggesting that vinorelbine alone is a suitable treatment option for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term analysis of survival in the European randomized trial comparing vinorelbine/cisplatin to vindesine/cisplatin and vinorelbine alone in advanced non-small cell lung cancer. Le Chevalier, T., Brisgand, D., Soria, JC., et al.[2019]

A systematic review of 23 randomized controlled trials found that while there are no significant differences in overall survival (OS) among various third-generation chemotherapy regimens for non-small cell lung cancer (NSCLC), pemetrexed combined with platinum-based therapy significantly improves OS compared to gemcitabine plus platinum.

Gefitinib showed a statistically significant improvement in progression-free survival (PFS) compared to both docetaxel plus platinum and paclitaxel plus platinum, indicating its potential as an effective first-line treatment option for patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the clinical effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer. Pilkington, G., Boland, A., Brown, T., et al.[2022]

Patients with metastatic non-small-cell lung cancer (NSCLC) typically have a very short median survival of 4 to 5 months with best supportive care, but cisplatin-based chemotherapy has been shown to provide a survival benefit, as indicated by a pivotal meta-analysis.

The addition of targeted agents, such as bevacizumab, to chemotherapy has demonstrated a survival advantage in chemotherapy-naive patients, suggesting that combining traditional chemotherapy with newer targeted therapies may improve outcomes for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line treatment for advanced non-small-cell lung cancer. Laskin, JJ., Sandler, AB.[2018]

In a study of 10 elderly patients with advanced refractory non-small-cell lung cancer (NSCLC) and low performance status, afatinib was found to be tolerable, with a median overall survival of 5.8 months despite a low objective response rate of 11%.

The most common side effect was grade 2 diarrhea, which led to some patients refusing to increase the dosage, suggesting that a lower starting dose of afatinib may be a safer option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and efficacy of afatinib at a low starting dosage in 10 elderly or low performance status patients with advanced refractory non-small-cell lung cancer. Kashiwabara, K., Semba, H., Fujii, S., et al.[2018]

Adjuvant chemotherapy is the standard treatment for early-stage non-small cell lung cancer (NSCLC) patients, particularly those with stage II, IIIA, or large IB tumors, providing a survival benefit of approximately 5% at 5 years, with some trials suggesting benefits of up to 10%.

Ongoing research is exploring the use of targeted agents and checkpoint inhibitors as potential adjuvant therapies, indicating a shift towards personalized treatment strategies based on tumor genetics rather than solely tumor size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Chemotherapy and Targeted Therapy in Early-Stage Non-Small Cell Lung Cancer. Gadgeel, SM.[2019]

Afatinib significantly prolongs progression-free survival (PFS) and time to treatment failure (TTF) in patients with advanced lung adenocarcinoma with activating EGFR mutations compared to gefitinib, although it does not improve overall survival (OS).

In second-line treatment for advanced squamous non-small cell lung cancer (NSCLC), afatinib shows significant improvements in both PFS and OS compared to erlotinib, demonstrating its efficacy across different lung cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afatinib: A Review in Advanced Non-Small Cell Lung Cancer. Keating, GM.[2018]

Afatinib is an effective oral treatment for adults with advanced non-small cell lung cancer (NSCLC) who have specific activating EGFR mutations, showing significantly prolonged progression-free survival compared to standard chemotherapy regimens in two phase III trials.

The drug has a manageable safety profile, with common side effects like diarrhea and rash being effectively controlled through dose adjustments, making it a valuable option for treatment-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afatinib: a review of its use in the treatment of advanced non-small cell lung cancer. Keating, GM.[2022]

Afatinib is an effective first-line treatment for advanced non-small cell lung cancer (NSCLC) with specific EGFR mutations, showing improved progression-free survival (PFS) compared to gefitinib and cisplatin-based chemotherapy, although it did not extend overall survival (OS) for all patients.

As a second-line treatment for advanced squamous NSCLC, afatinib significantly prolonged both PFS and OS compared to erlotinib, demonstrating its efficacy regardless of EGFR mutation status, and it has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afatinib in advanced NSCLC: a profile of its use. Deeks, ED., Keating, GM.[2020]

Citations

1. withpower.com withpower.com/trial/phase-3-lung-neoplasms-8-2021-822f5

Afatinib + Prednisone for Lung Cancer · Info for Participants Afatinib aims to stop cancer growth by targeting specific proteins, while prednisone helps reduce inflammation and immune reactions. The goal is to find out if ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-12550

Afatinib in Combination with Prednisone for the Treatment ... This phase II trial tests whether afatinib in combination with prednisone works to shrink tumor in patients with squamous non-small cell lung cancer that ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6473268/

Efficacy and Safety of Afatinib for EGFR-mutant Non-small ... The median progression-free survival (PFS) time for afatinib, gefitinib, and erlotinib was 19.1 months, 13.7 months, and 14.0 months, respectively (p=0.001).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01415011

Efficacy and Safety Study of Afatinib to Treat Lung Cancer ... The purpose of this study is to examine the efficacy and safety of using afatinib (BIBW 2992) to treat non-small cell lung cancer patients considered unfit ...

5. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/gilotrif/squamous-mnsclc

Efficacy for Squamous mNSCLC | GILOTRIF® (afatinib) ... Review GILOTRIF® clinical data for your metastatic squamous NSCLC patient progressing after platinumbased chemotherapy. See ISI and full PI.