Afatinib for Advanced Skin Cancer

Overseen By Ashley Paneto-Matos

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Corticosteroids

Disqualifiers: Severe liver impairment, Pregnancy, 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: 8

Duration: Up to 1 year

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Afatinib, a daily medication, can treat advanced skin cancer, specifically cutaneous squamous cell carcinoma (cSCC), which cannot be treated with further surgery or radiation. Participants will take Afatinib and undergo regular check-ups, including scans and biopsies, to assess the treatment's effectiveness. Those with cSCC that has spread or cannot be surgically removed, and who have already tried other treatments like immunotherapy, may be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be at least 2 weeks from any prior systemic therapy before starting the study treatment.

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

Research shows that afatinib, a cancer treatment, can cause some side effects. Studies have found that patients might experience skin rash, diarrhea, and other skin problems. Some reports also mention a loss of appetite, nausea, and vomiting.

However, afatinib is already approved for other uses, indicating it is generally safe when used properly. Awareness of these side effects can aid in better management. Considering these factors is important when deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike most treatments for advanced skin cancer, which typically involve chemotherapy or targeted therapies against specific mutations, afatinib is a pan-ErbB inhibitor. This means it targets multiple receptors in the ErbB family, potentially offering broader anti-cancer effects. Researchers are excited about afatinib because it may work for patients whose tumors have not responded to other treatments by attacking cancer cell growth through a different pathway. Additionally, its once-daily oral administration offers a convenient alternative to more invasive treatment methods.

What evidence suggests that Afatinib might be an effective treatment for advanced skin cancer?

Research has shown that Afatinib may help treat certain cancers. In studies with non-small cell lung cancer (NSCLC), Afatinib stopped the cancer from worsening for about 7.3 months on average. Earlier research also found that it controlled the disease in 87.6% of NSCLC patients and shrank tumors in 58.9% of them. Afatinib blocks specific proteins that aid cancer cell growth. This trial will investigate whether Afatinib might also be effective in treating advanced skin cancer similarly. ^{6 7 8 9 10}

Who Is on the Research Team?

Zeynep Eroglu

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced cutaneous squamous cell carcinoma (cSCC) not suitable for surgery/radiation, who've had prior immunotherapy if eligible. Must have good organ function and performance status, a measurable lesion, and be at least 2 weeks post any major treatment or surgery. Those with treated brain metastases can join; however, those with severe liver issues, mixed cancer types, untreated HIV/HCV or pregnancy are excluded.

Inclusion Criteria

I am a woman who can have children and have a negative pregnancy test, or I agree to use effective birth control.

I can have a biopsy before and during treatment.

I haven't had any major treatments or surgery for at least 2 weeks.

Exclusion Criteria

I have HIV with undetectable viral load or cured hepatitis C.

My cancer is mainly invasive cutaneous squamous cell carcinoma.

Pregnancy or breast feeding

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 once a day. Each cycle is 4 weeks. CT imaging and/or digital photography is done at baseline and every 8 weeks. Tumor biopsies are conducted at baseline, at 4 weeks, and at disease progression if feasible.

Up to 1 year

Baseline, every 8 weeks for imaging, biopsies at specified intervals

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-related adverse events up to 40 days after end of treatment.

40 days

Long-term follow-up

Participants are monitored for progression-free survival and overall survival.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Afatinib

Trial Overview

The trial is testing the effectiveness of Afatinib 40 MG in treating advanced cSCC. Participants will receive this medication to see if it improves their condition compared to previous treatments they may have received.

How Is the Trial Designed?

Group I: Afatinib Intervention Experimental Treatment 1 Intervention

Participants will receive afatinib 40 mg once a day. Each cycle is 4 weeks. They will have CT imaging (and/or digital photography) done at baseline and every 8 weeks while on treatment. Participants will have a baseline and on-treatment (at 4 weeks) tumor biopsy, and a biopsy at disease progression if feasible. Patients may remain on treatment as long as they are deriving clinical benefit, until disease progression or intolerable 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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

A combination therapy using afatinib and crizotinib effectively targets both MET and ERBB family receptors in disseminated cutaneous malignant melanoma (CMM), promoting cell death and reducing tumor growth in various models, including patient-derived cell lines and an in vivo mouse model.

This combination therapy shows minimal toxicity and is effective regardless of BRAF/NRAS mutation status, making it a promising option for CMM patients, especially those who have developed resistance to existing BRAF inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining ERBB family and MET inhibitors is an effective therapeutic strategy in cutaneous malignant melanoma independent of BRAF/NRAS mutation status. Das, I., Wilhelm, M., Höiom, V., et al.[2021]

In a study of 31 skin lesions from patients treated with sorafenib, a range of lesions from benign to malignant was observed, indicating that sorafenib may promote skin tumor development, particularly in hair follicles.

Sorafenib treatment was found to increase keratinocyte proliferation and activate the MAP kinase pathway, suggesting a mechanism by which it may contribute to the formation of skin tumors, especially in the presence of preexisting genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin tumors induced by sorafenib; paradoxic RAS-RAF pathway activation and oncogenic mutations of HRAS, TP53, and TGFBR1. Arnault, JP., Mateus, C., Escudier, B., et al.[2021]

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]

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]

In a phase II trial involving 29 patients with advanced melanoma who had previously failed immunotherapy, the combination of apatinib and temozolomide showed a median progression-free survival of 5.0 months and a median overall survival of 10.1 months, indicating promising efficacy.

The treatment was generally well-tolerated, with manageable side effects; serious adverse events were limited, and no treatment-related deaths occurred, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of apatinib combined with temozolomide in patients with advanced melanoma after failure of immunotherapy. Zhou, L., Yang, Y., Si, L., et al.[2023]

Advanced melanoma is a leading cause of cancer-related deaths in the USA, with increasing incidence rates, primarily driven by UV damage and genetic factors.

Immunotherapies, particularly the combination of CTLA4 and PD-1 inhibitors, show the highest activity for treating metastatic melanoma, offering potential durable responses, while targeted MAPK inhibitors are recommended for patients with BRAF mutations and rapidly progressing disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Promise of Molecularly Targeted and Immunotherapy for Advanced Melanoma. Margolin, K.[2018]

Sorafenib, an oral multikinase inhibitor targeting Raf kinases and VEGF receptors, has shown limited efficacy as a single-agent therapy for advanced metastatic melanoma, indicating a need for new treatment strategies.

While combination therapies with sorafenib and chemotherapeutic agents like dacarbazine and temozolomide have shown more promise in phase II studies, these findings require further validation in larger phase III trials before establishing sorafenib as a standard treatment for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic melanoma: scientific rationale for sorafenib treatment and clinical results. Egberts, F., Kahler, KC., Livingstone, E., et al.[2018]

Minocycline petrolatum effectively prevents and repairs skin disorders caused by afatinib, a second-generation EGFR-TKI, in a mouse model, indicating its potential as a treatment for patients experiencing these side effects.

The study demonstrated significant improvement in skin condition and transepidermal water loss (TEWL) after minocycline application, suggesting it could enhance the quality of life for non-small cell lung cancer patients undergoing afatinib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer. Sano, K., Nakadate, K., Hanada, K.[2021]

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 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.

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.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4888861/

Spotlight on afatinib and its potential in the treatment of ...

In several preclinical studies, afatinib has been shown to be more effective in suppressing the tyrosine kinase activity of both wild-type and activated EGFR or ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05070403?tab=history&a=4

Record History | ver. 4: 2022-12-30 | NCT05070403

Study of Afatinib in Advanced Cutaneous Squamous Cell Carcinoma. ClinicalTrials.gov ID NCT05070403. Sponsor H. Lee Moffitt Cancer Center and Research Institute.

4.

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 ...

Results showed that the overall median time on treatment for patients who received second-line afatinib was 7.3 months (95% CI, 5.2-8.1).

5.

ascopubs.org

ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.e21134

Efficacy and safety of afatinib in advanced non-small cell ...

The efficacy of DCR and ORR were 87.6 % (81.5, 92.7) and 58.9 % (48.8, 68.7). The pooled medium PFS was 12.45 months (10.36, 14.54), medium TTF ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11748754/

Dermatologic Adverse Events Following Afatinib in a ...

Study by Zhao et al show that afatinib had the highest risk of rash, diarrhea, stomatitis, paronychia, and pruritus, but the lowest risk of ...

7.

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%).

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8710163/

Efficacy and Safety of Afatinib in the Treatment ...

The pooled median progression-free survival (PFS) was 12.4 (10.3, 14.5) months, mean time to failure (TTF) was 15.4 (13.6, 17.2) months, and median overall ...

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05070403

Study of Afatinib in Advanced Cutaneous Squamous Cell ...

A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

10.

ar.iiarjournals.org

ar.iiarjournals.org/content/38/3/1783

Skin Rash Can Be a Useful Marker for Afatinib Efficacy

In the present study, afatinib as a first-line EGFR-TKI was effective and safe. Furthermore, the severity of skin rash may be useful as a marker of afatinib ...