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

Recruiting at 637 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

174 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II/III trial studies how well afatinib dimaleate with cetuximab works and compares it with afatinib dimaleate alone in treating patients with newly diagnosed stage IV or recurrent (has come back), epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer. Afatinib dimaleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. It is not yet known whether afatinib dimaleate is more effective when given alone or with cetuximab in treating patients with non-small cell lung cancer.

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.

What data supports the effectiveness of the drug Afatinib Dimaleate combined with Cetuximab for treating non-small cell lung cancer?

Research shows that combining afatinib with cetuximab has promising results in treating non-small cell lung cancer with specific mutations, achieving a 29% response rate and extending the time patients live without the disease getting worse to about 4.7 months. ^{1 2 3 4 5}

Is the combination of Afatinib and Cetuximab safe for humans?

Afatinib, used for treating non-small cell lung cancer, can cause side effects like diarrhea, skin rash, and mouth sores. Managing these side effects is important to maintain quality of life. No specific safety data for the combination with Cetuximab is provided in the available research. ^{6 7 8 9 10}

How is the drug Afatinib Dimaleate different from other treatments for non-small cell lung cancer?

Afatinib Dimaleate, when combined with cetuximab, offers a novel approach by targeting the epidermal growth factor receptor (EGFR) in two ways: using a tyrosine kinase inhibitor (afatinib) and a monoclonal antibody (cetuximab). This dual targeting is particularly promising for patients with EGFR-mutated lung cancer who have developed resistance to other EGFR inhibitors like gefitinib or erlotinib. ^{1 2 3 4 11}

Research Team

Sarah Goldberg

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib. [2018]

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

First-Line Afatinib plus Cetuximab for EGFR-Mutant Non-Small Cell Lung Cancer: Results from the Randomized Phase II IFCT-1503 ACE-Lung Study. [2022]

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

Afatinib Therapy: Practical Management of Adverse Events With an Oral Agent for Non-Small Cell Lung Cancer Treatment. [2022]

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

A HER 1-2 punch: dual EGFR targeting deals resistance a deadly blow. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan. [2023]

6. Egypt pubmed.ncbi.nlm.nih.gov

Survival Outcomes of Nonsmall Cell Lung Cancer Patients Treated with Afatinib Who Are Affected by Early Adverse Events. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Survival of chemo-naïve patients with EGFR mutation-positive advanced non-small cell lung cancer after treatment with afatinib and bevacizumab: updates from the Okayama Lung Cancer Study Group Trial 1404. [2021]

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

Multi-disciplinary proactive follow-up algorithm for patients with advanced NSCLC receiving afatinib. [2020]

9. China 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. [2022]

10. Spain pubmed.ncbi.nlm.nih.gov

[Toxicity associated with EGRF inhibition: review and key aspects in the management of afatinib]. [2018]

11. United States 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. [2018]