Afatinib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: EGFR inhibitors

Disqualifiers: Lung cancer, Glioblastoma, Interstitial lung, 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: 5

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a drug called afatinib in treating cancer with certain genetic changes. Afatinib targets a specific mutation in the EGFR gene, which can cause cancer cells to grow. The goal is to determine if afatinib can slow or stop this growth. Suitable candidates are patients whose cancer has specific EGFR mutations, excluding certain types like non-small cell lung cancer or glioblastoma. 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 information does not specify if you need to stop taking your current medications. However, you must not have had prior treatment with an EGFR tyrosine kinase inhibitor (a type of cancer medication).

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

Research has shown that afatinib is usually well-tolerated by patients, but like any medication, it can have side effects. Earlier studies reported common side effects such as decreased appetite, nausea, and vomiting, affecting about 29%, 25%, and 23% of patients, respectively. Rare but serious skin reactions, including severe skin damage, have also been reported. Monitoring for any skin changes during treatment is important. Despite these risks, many patients have used afatinib, and the FDA has approved it for certain types of cancer, indicating that its safety is well understood. Always discuss any concerns or symptoms with your doctor during treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cancer, which often include chemotherapy and targeted therapies like EGFR inhibitors, afatinib is unique because it irreversibly blocks a range of signaling pathways involved in cancer cell growth. Most treatments target specific points, but afatinib goes a step further by inhibiting multiple members of the ErbB family of receptors, which are key players in tumor growth and survival. This broad-spectrum inhibition could potentially lead to more comprehensive and effective cancer control. Researchers are excited about afatinib because it offers a new way to tackle tumors that may not respond well to existing therapies.

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

Research has shown that afatinib, which participants in this trial will receive, may help treat certain cancers with specific genetic changes, especially mutations in the EGFR gene. Studies have found that afatinib works well as a first treatment for patients with lung adenocarcinoma, particularly those with rare EGFR mutations. In these patients, the cancer did not progress for an average of 13 months. Another study found that 59.5% of patients experienced either stabilization or improvement in their cancer. These results suggest that afatinib can help slow or stop cancer from spreading in patients with these specific genetic changes. ^{4 6 7 8 9}

Who Is on the Research Team?

Scott N Gettinger

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for cancer patients with specific genetic changes in the EGFR gene. It's open to those with various cancers like lymphoma, solid tumors, and multiple myeloma who meet certain health standards.

Inclusion Criteria

My diarrhea is mild or nonexistent.

Pre-treatment LVEF determination in patients without known left ventricular dysfunction is NOT required

Patients must not have known hypersensitivity to afatinib or similar compounds

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Treatment

Participants receive afatinib orally once daily on days 1-28 of each cycle. 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

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up includes CT or MRI as clinically necessary.

3 years

Every 3 months for 2 years, then every 6 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Afatinib

Trial Overview The study is testing afatinib, a kinase inhibitor medication that targets mutated EGFR genes to halt or slow cancer cell growth. The trial involves tests like MRI, echocardiography, biopsies, biospecimen collection, radionuclide imaging, and CT scans.

How Is the Trial Designed?

Group I: Treatment (afatinib) Experimental Treatment 7 Interventions

Patients receive afatinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients may also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.

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 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]

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]

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. e-crt.org e-crt.org/journal/view.php?doi=10.4143/crt.2023.493

Updated Analysis of the RESET Study In this final report, the estimated median TOT was 15.0 months on afatinib and 11.9 months on osimertinib. The results from previous randomized controlled ...

5. 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 ...

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. 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 ...

8. 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 ...

9. 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) non ... Safety and efficacy have not been established. Geriatric. Appropriate ...