Afatinib +/− Cetuximab for Non-Small Cell Lung Cancer

Not currently recruiting at 645 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: SWOG Cancer Research Network

Must not be taking: EGFR inhibitors

Disqualifiers: Interstitial lung disease, Cardiovascular abnormalities, Hepatitis, 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: 28 days per cycle, repeated

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for non-small cell lung cancer that has spread or recurred and is positive for certain EGFR mutations (cell changes that can lead to cancer). It compares the effectiveness of afatinib dimaleate alone to afatinib dimaleate combined with cetuximab, a monoclonal antibody targeting cancer cells. The goal is to determine if adding cetuximab improves treatment outcomes. The trial seeks participants with stage IV or recurrent non-small cell lung cancer with specific genetic mutations who have not received prior treatment for advanced disease. As a Phase 2 trial, the 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 taking your current medications. However, you must not have received any prior systemic anticancer therapy for advanced or metastatic disease, and you cannot be planning to receive any other investigational agents during the trial.

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

Research has shown that afatinib dimaleate is generally safe for people with non-small cell lung cancer. One study found serious side effects in about 7.3% of patients, indicating most tolerated it well. No new safety issues emerged when used in everyday settings.

When combined with cetuximab, some studies indicate afatinib causes more side effects than when used alone. However, this combination still effectively fights tumors and might help prevent cancer from becoming resistant to treatment, despite the increased risk of side effects.

Both treatments are under study, but afatinib already has FDA approval for other lung cancer uses, indicating a known safety record. As with any treatment, discussing potential risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about afatinib dimaleate, with or without cetuximab, for treating non-small cell lung cancer because it offers a unique approach compared to the standard chemotherapy and immunotherapy options. Afatinib dimaleate works as a tyrosine kinase inhibitor, specifically targeting the epidermal growth factor receptor (EGFR), which plays a crucial role in the growth and spread of cancer cells. This targeted action can lead to more precise treatment with potentially fewer side effects. In the combination arm, cetuximab adds an extra layer by also targeting EGFR but through a different mechanism, which might enhance the overall effectiveness against resistant cancer cells.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that afatinib, which participants in this trial may receive, effectively treats non-small cell lung cancer (NSCLC) with specific genetic changes called EGFR mutations. Studies indicate that patients taking afatinib live for more than four years on average and have a high response rate of 77.2%. In this trial, some participants will receive afatinib alone, while others will receive a combination of afatinib and cetuximab. Adding cetuximab, a medicine that targets cancer cells, might enhance afatinib's effectiveness. Early research suggests that using afatinib and cetuximab together can help prevent or slow the cancer's resistance to treatment. While both treatments show promise individually, researchers continue to study their combined effectiveness. ^{1 6 7 8 9}

Who Is on the Research Team?

Sarah Goldberg

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with stage IV or recurrent non-small cell lung cancer (NSCLC) that tests positive for EGFR mutations. Participants must be able to take oral medication, have not had major surgery recently, and cannot have active hepatitis B/C or HIV. They should not have significant heart issues, gastrointestinal disorders causing diarrhea, or a history of allergic reactions to similar drugs. Women who are pregnant or nursing are excluded.

Inclusion Criteria

My cancer has specific EGFR mutations and was tested in a certified lab.

Prestudy history and physical must be obtained with 28 days prior to registration

I've had a brain scan in the last 42 days showing no symptoms of brain cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive afatinib dimaleate orally once daily and cetuximab intravenously on specified days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle, repeated

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Afatinib Dimaleate
• Cetuximab

Trial Overview The study compares the effectiveness of afatinib dimaleate alone versus combined with cetuximab in treating NSCLC with EGFR mutations. Afatinib blocks enzymes needed for tumor growth while cetuximab targets certain cells to inhibit tumor expansion.

How Is the Trial Designed?

Group I: Arm I (afatinib dimaleate, cetuximab) Experimental Treatment 3 Interventions

Patients receive afatinib dimaleate PO QD on days 1-28 and cetuximab IV over 2 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (afatinib dimaleate) Active Control 2 Interventions

Patients receive afatinib dimaleate as in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of afatinib and nimotuzumab showed an acceptable safety profile in 50 advanced non-small cell lung cancer patients, with 16% experiencing grade 3 toxicities, primarily skin rash and diarrhea.

This treatment resulted in a 23% overall response rate, with a median progression-free survival of 4.0 months and overall survival of 11.7 months, indicating promising antitumor activity in patients resistant to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of Afatinib in Combination with Nimotuzumab in Non-Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib. Lee, JY., Sun, JM., Lim, SH., et al.[2018]

In a study of 468 patients with advanced non-small cell lung cancer (NSCLC) treated with afatinib, early rash was significantly associated with improved overall survival (OS), suggesting it may indicate better long-term outcomes.

Early diarrhea was linked to improved progression-free survival (PFS), indicating that certain early adverse events can provide insights into treatment efficacy, although rash was the only event associated with OS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes of Nonsmall Cell Lung Cancer Patients Treated with Afatinib Who Are Affected by Early Adverse Events. Logan, JM., Brooks, DA., Rowland, A., et al.[2022]

In a phase II trial involving 30 patients with advanced non-squamous non-small cell lung cancer (NSCLC), the combination of apatinib and docetaxel resulted in a disease control rate of 96.6% and a partial remission rate of 27.6%.

The treatment was found to be tolerable, with most adverse events being mild to moderate (grade 1-2), including hypertension and hand-foot syndrome, indicating that apatinib plus docetaxel is a safe option for patients with wild-type EGFR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of apatinib and docetaxel in treating advanced non-squamous non-small cell lung cancer patients with wild-type EGFR: a multi-center, phase II trial. Song, Y., Miao, L., Wang, Z., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6204616/

Afatinib in the first-line treatment of patients with non-small cell ... The clinical activity of afatinib has been also confirmed in real-life studies. A recent retrospective Taiwanese cohort study reported a 77.2% ORR and a median ...

2. ar.iiarjournals.org ar.iiarjournals.org/content/42/4/2145

Real-world Afatinib Outcomes in Advanced Non–small Cell ... The median overall survival (OS) was 61.8 months for patients with T790M mutation undergoing later-line osimertinib compared with 30.1 months for patients ...

3. nature.com nature.com/articles/s41416-024-02901-6

Long term efficacy of first-line afatinib and the clinical utility ... Afatinib is a viable treatment option for tissue or ctDNA-detected EGFR mutant NSCLC comorbid patients, with a proportion achieving long-term clinical benefit.

4. tlcr.amegroups.org tlcr.amegroups.org/article/view/80829/html

Real-world first-line afatinib for advanced EGFR mutation ... Conclusions: Afatinib was effective in Korean patients with EGFR mutation-positive NSCLC with median OS over 4 years. The presence of baseline ...

5. cancernetwork.com cancernetwork.com/view/afatinib-effective-nsclc-patients-rare-egfr-mutations

Afatinib Effective in NSCLC Patients With Rare EGFR ... Median overall survival (OS) was 19.4 months (95% CI: 16.4–26.9) in group one, 14.9 months (8.1–24.9) in group two, and 9.2 months (4.1–14.2) in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02364609

Pembrolizumab and Afatinib in Patients With Non-small ... Afatinib dimaleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and afatinib dimaleate ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10705085/

Real-World Treatment Outcomes and Safety of Afatinib in ... In this study, we observed the clinical outcomes of 2.1 months TTF and DCR of 59.5% with no new safety signals in patients with LSCC treated ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291824000870

Assessing Patient Risk, Benefit, and Outcomes in Drug ... We investigated published afatinib clinical trials to assess risk and benefit profiles for the drug in its approved indication of non–small-cell lung cancer as ...

9. e-crt.org e-crt.org/journal/view.php?doi=10.4143/crt.2018.117

Efficacy and Safety of Afatinib for EGFR-mutant Non-small ... Overall toxicity profiles of the three drugs were comparable, though more grade 3 or 4 toxicities were detected in afatinib (7.3%) compared with ...