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

Trial Summary

What is the purpose of this trial?

Primary Objective: To assess the activity of Afatinib in patients with persistent or recurrent uterine serous carcinoma overexpressing HER2/neu with the frequency of patients who survive progression-free for at least 6 months after initiating therapy. Secondary Objectives: To assess objective response rate and durable disease control rate. To assess overall survival. To assess the safety profile of Afatinib in uterine serous carcinoma patients.

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.

What evidence supports the effectiveness of the drug Afatinib for uterine cancer?

There is a case report showing that Afatinib helped a patient with HER2-amplified endometrial cancer, a type of uterine cancer, by reducing tumor size and levels of cancer markers after other treatments failed. This suggests Afatinib might be beneficial for similar cases. ^{1 2 3 4 5}

Is Afatinib generally safe for human use?

Afatinib, also known as Gilotrif, is generally considered safe for human use, with a manageable safety profile. Common side effects include diarrhea and skin rash, which are typically managed by adjusting the dose or delaying treatment. ^{1 2 3 6 7}

How is the drug Afatinib unique for treating uterine cancer?

Afatinib is unique because it targets the ErbB family of proteins, which are involved in cell growth and division, and is particularly effective in cancers with HER2 amplification, a specific genetic change. This makes it different from standard chemotherapy, as it works by blocking signals that tell cancer cells to grow, offering a new option for patients with HER2-amplified uterine cancer who have not responded to other treatments. ^{1 2 3 4 5}

Research Team

Alessandro Santin

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Afatinib in advanced NSCLC: a profile of its use. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

Afatinib. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Afatinib: a review of its use in the treatment of advanced non-small cell lung cancer. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy of afatinib in a HER2 amplification-positive endometrioid adenocarcinoma patient- a case report. [2020]

5. United States 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. [2021]

6. England 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. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Severe Gastrointestinal Toxicity Following the Use of Gilteritinib: A Case Series and Analysis of Postmarketing Surveillance Data. [2023]