Afatinib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Tyrosine kinase inhibitors

Disqualifiers: Hypersensitivity to afatinib, Interstitial lung disease, Non-small cell lung cancer, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests afatinib, a drug that may stop cancer growth by blocking a protein called HER2, which some cancers require to grow. The main goal is to determine if afatinib can shrink tumors or prevent them from enlarging in patients with specific genetic changes in their cancer. Suitable candidates for this trial have cancer with certain HER2 mutations and have not previously used similar drugs. Participants should not have non-small cell lung cancer or certain heart or lung conditions. 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 information does not specify if you need to stop taking your current medications. However, you cannot have taken certain medications like afatinib or other similar drugs before joining the trial.

Is there any evidence suggesting that afatinib is likely to be safe for humans?

Research has shown that afatinib has been tested in many patients, with some common side effects reported. These include loss of appetite, nausea, and vomiting, affecting about a quarter to a third of patients. While uncomfortable, these side effects are usually manageable.

However, some serious but rare skin reactions have also been noted, such as toxic epidermal necrolysis and Stevens-Johnson syndrome. If these occur, stopping the treatment is necessary.

Afatinib is already approved for other conditions, indicating its safety has been well-studied. However, individual experiences can vary. Anyone considering the trial should discuss these potential effects with a healthcare provider to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for certain types of cancer, which often include chemotherapy and radiation, afatinib is a targeted therapy that works by specifically inhibiting the activity of certain proteins involved in cancer cell growth. This approach can potentially lead to fewer side effects compared to traditional therapies, as it aims to attack cancer cells more precisely. Researchers are excited about afatinib because it might offer a more effective option for patients whose tumors have specific genetic mutations, providing a personalized treatment strategy that could improve outcomes.

What evidence suggests that afatinib might be an effective treatment for cancer?

Research has shown that afatinib can effectively treat some cancers, particularly certain lung cancers with specific genetic changes. For instance, patients with lung adenocarcinoma and certain EGFR mutations have responded well to afatinib, with their cancer not worsening for about 13 months on average. In everyday medical practice, afatinib has also benefited patients with advanced squamous lung cancer, even after other treatments like chemotherapy. Additionally, afatinib is usually well-tolerated, with manageable side effects. These findings suggest that afatinib may help shrink tumors or halt their growth in cancers with HER2 mutations. ^{3 6 7 8 9}

Who Is on the Research Team?

Philippe L Bedard

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for cancer patients with specific HER2 genetic changes. They must have normal heart function, controlled diarrhea, and adequate kidney function. People with hypersensitivity to afatinib, lung disease history, or previous treatment with certain tyrosine kinase inhibitors are excluded.

Inclusion Criteria

I currently have mild or no diarrhea.

My recent ECG showed no significant heart issues.

My tumor has an activating HER2 mutation.

Exclusion Criteria

I have not taken any medication known to target HER2.

I have never had interstitial lung disease.

Patients must not have known hypersensitivity to afatinib or compounds of similar chemical or biologic composition

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive afatinib dimaleate orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Every 2 cycles for the first 26 cycles, then every 3 cycles thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months if less than 2 years from study entry, and then every 6 months for year 3.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Afatinib

Trial Overview The trial tests Afatinib Dimaleate's effectiveness on cancers with HER2 mutations. It aims to see if this drug can shrink the tumors or halt their growth by blocking a protein essential for cancer cell development.

How Is the Trial Designed?

Group I: Treatment (afatinib dimaleate) Experimental Treatment 1 Intervention

Patients receive afatinib dimaleate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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]

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 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 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. 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 ...

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

Long term efficacy of first-line afatinib and the clinical utility ... The effect of afatinib was greatest for the 16 patients with exon 19 deletion or L858R, with median PFS of 13.0 months (95% CI 5.9-39.3) and ...

3. 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.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7418472/

The effectiveness of afatinib in patients with lung ... Afatinib is an effective first-line treatment for patients with lung adenocarcinoma harboring complex EGFR mutations, especially those with uncommon mutation ...

5. onclive.com onclive.com/view/real-world-data-show-afatinib-as-effective-safe-in-second-line-metastatic-squamous-lung-cancer

Real World Data Show Afatinib as Effective, Safe in ... Afatinib was found to be effective and well tolerated when used as a second-line treatment in patients with metastatic squamous carcinoma of the lung.

6. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/gilotrif/safety

Safety & Adverse Reactions | GILOTRIF® (afatinib) tablets Other clinically important adverse reactions observed in patients treated with GILOTRIF included: decreased appetite (29%), nausea (25%), and vomiting (23%).

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/201292s014lbl.pdf

GILOTRIF® (afatinib) tablets, for oral use - accessdata.fda.gov The data in the Warnings and Precautions section reflect exposure to GILOTRIF for clinically significant adverse reactions in 4257 patients enrolled in LUX-Lung ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/afatinib-oral-route/description/drg-20061227

Afatinib (oral route) - Side effects & dosage Afatinib is used to treat metastatic (cancer that has already spread) ... Safety and efficacy have not been established. Geriatric.

9. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/gilotrif/important-safety-information

Important Safety Information | GILOTRIF® (afatinib) tablets Postmarketing cases of toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS) have been reported in patients receiving GILOTRIF. Discontinue ...