Afatinib for Uterine Cancer

(Afatinib Trial)

Overseen By Alessandro Santin

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Irreversible tyrosine kinase inhibitors

Disqualifiers: Cardiac disease, Hypertension, HIV, 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: 4

Duration: 12 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Afatinib (Gilotrif) can benefit patients with a specific type of uterine cancer that has returned or persists. The researchers aim to determine if the treatment can prevent cancer progression for at least six months, while also assessing overall survival and the drug's safety. Suitable candidates for this trial have persistent or recurrent uterine cancer with a tumor that tests positive for HER2/neu and have measurable disease. Previous treatments for cancer do not necessarily disqualify participation, provided there are no major heart issues or other serious health problems. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires a 2-week period without taking trastuzumab before starting Afatinib. For other medications, the protocol does not specify if you need to stop taking them.

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

Research shows that afatinib is under study for its safety and effectiveness in treating uterine cancer. In earlier studies with patients who have HER2-positive cancers, afatinib showed promise. However, understanding possible side effects is important. Patients taking afatinib commonly reported decreased appetite, nausea, and vomiting, affecting about 29%, 25%, and 23% of patients, respectively. While afatinib might be effective, it could also cause discomfort. Always discuss potential risks and benefits with a doctor before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for uterine cancer?

Afatinib is unique because it targets specific proteins involved in the growth of cancer cells, known as tyrosine kinases. This targeted approach is different from traditional chemotherapy, which typically attacks both healthy and cancerous cells, leading to more side effects. Researchers are excited about afatinib because it offers a more precise treatment option for uterine cancer, potentially improving effectiveness while reducing side effects. Additionally, afatinib is taken orally, which can be more convenient for patients compared to intravenous chemotherapy.

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

Research has shown that Afatinib, the treatment under study in this trial, holds promise for treating uterine serous carcinoma, particularly in patients with high levels of the HER2/neu protein. In studies, Afatinib proved effective against this type of uterine cancer, which often resists chemotherapy. Specifically, about 30% of patients with recurring uterine serous carcinoma experienced tumor shrinkage or halted growth after treatment. These findings suggest that Afatinib could be a valuable option for managing this challenging form of cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Alessandro Santin

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with persistent or recurrent HER2-positive uterine serous carcinoma. Participants must have measurable disease, recovered from prior treatments, adequate organ and bone marrow function, and an ECOG performance status of 0 or 1. Women of childbearing age need a negative pregnancy test and must use contraception.

Inclusion Criteria

My cancer is mostly uterine papillary serous adenocarcinoma.

I have had several treatments for my recurring uterine cancer.

Must have signed an approved consent

Exclusion Criteria

Patients known to be seropositive for HIV and active hepatitis, even if liver function studies are in the eligible range

I have seizures or a brain condition that is not well-controlled.

I have been treated with a specific type of lung cancer medication before.

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 every 21 days for 4 cycles

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Afatinib

Trial Overview The trial tests Afatinib's effectiveness in patients with HER2-positive uterine serous carcinoma by measuring progression-free survival at six months, overall response rate, durable disease control rate, overall survival, and safety profile.

How Is the Trial Designed?

Group I: Afatinib Experimental Treatment 1 Intervention

Afatinib 40 mgs., Q 21 Day times 4 Cycles

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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

In a phase II trial involving 32 eligible patients with advanced endometrial cancer, nintedanib showed a low overall response rate of 9.4%, indicating limited efficacy as a single agent.

Despite its lack of sufficient activity alone, nintedanib may have potential when combined with paclitaxel, particularly in patients with specific p53 mutations, suggesting a need for further research in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study. Dizon, DS., Sill, MW., Schilder, JM., et al.[2021]

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 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]

Gilteritinib is an effective treatment for adults with relapsed or refractory acute myeloid leukemia (AML) with FLT3 mutations, showing advantages in survival and a generally favorable safety profile.

While gilteritinib is associated with common side effects like diarrhea and nausea, serious gastrointestinal events such as GI hemorrhage and perforation have been reported, highlighting the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Gastrointestinal Toxicity Following the Use of Gilteritinib: A Case Series and Analysis of Postmarketing Surveillance Data. Gozzo, L., Nardo, A., Brancati, S., et al.[2023]

Gilteritinib has been approved in the EU as a monotherapy for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, showing a significant improvement in overall survival (9.3 months) compared to salvage chemotherapy (5.6 months) in a phase III study with 371 participants.

The safety profile of gilteritinib is considered manageable, with common side effects including increases in liver enzymes and creatine phosphokinase, as well as gastrointestinal and general symptoms like fatigue and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Gilteritinib (Xospata) for the Treatment of Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an FLT3 Mutation. Tzogani, K., Røshol, H., Olsen, HH., et al.[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 showed clinical efficacy in a patient with HER2-amplified stage IIIC endometrial cancer, leading to a partial response after two months of treatment, which included a significant reduction in tumor markers and pulmonary lesions.

This case emphasizes the importance of comprehensive mutational profiling in endometrial cancer management, as it guided the use of afatinib in a heavily pre-treated patient with multiple metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of afatinib in a HER2 amplification-positive endometrioid adenocarcinoma patient- a case report. Zhou, L., Ren, Y., Wang, X., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4453741/

Afatinib demonstrates remarkable activity against HER2 ... Afatinib may be highly effective against HER2/neu-amplified chemotherapy-resistant USC. The investigation of afatinib in patients harbouring ...

2. yalemedicine.org yalemedicine.org/clinical-trials/usc-afatinib

A Phase II Evaluation of Afatinib To assess the activity of Afatinib in patients with persistent or recurrent uterine serous carcinoma overexpressing HER2/neu.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2017-00360

Afatinib in Treating Patients with Recurrent Stage I-IV ... This phase II trial studies how well afatinib works in treating patients with stage I-IV HER2 positive uterine cancer that has come back after a period of ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24004468

Uterine serous carcinoma: key advances and novel ... In a recent phase II study of 27 women with recurrent uterine serous carcinoma, the overall response rate to this therapy was nearly 30%, although side effects ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02491099

NCT02491099 | A Phase II Evaluation of Afatinib in ... Primary Objective: To assess the activity of Afatinib in patients with persistent or recurrent uterine serous carcinoma overexpressing HER2/neu with the ...

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%).