Afatinib for Uterine Cancer
(Afatinib Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Yale University
Must not be taking: Irreversible tyrosine kinase inhibitors
Disqualifiers: Cardiac disease, Hypertension, HIV, others
No Placebo Group
Prior Safety Data
Approved in 4 Jurisdictions
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?
Is Afatinib generally safe for human use?
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.12345
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
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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.
See 4 more
Trial 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 (Tyrosine Kinase Inhibitor)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: AfatinibExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale New Haven HospitalNew Haven, CT
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Who Is Running the Clinical Trial?
Yale UniversityLead Sponsor
Boehringer IngelheimIndustry Sponsor
References
Afatinib in advanced NSCLC: a profile of its use. [2020]Afatinib [Giotrif® (EU); Gilotrif® (USA)] is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases that provides an important first-line treatment option for advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations (i.e. EGFRactMUT+), and an additional treatment option for squamous NSCLC that has progressed following first-line platinum-based chemotherapy. Relative to gefitinib in the first-line treatment of EGFRactMUT+ advanced lung adenocarcinoma, afatinib prolonged progression-free survival (PFS) and time to treatment failure (TTF), but not overall survival (OS). Afatinib also prolonged PFS, but not OS, versus cisplatin-based chemotherapy in this setting; however, afatinib improved OS versus chemotherapy in the subgroup of patients with deletions in exon 19. As a second-line treatment for advanced squamous NSCLC, afatinib prolonged PFS and OS compared with erlotinib, regardless of EGFR mutation status. Afatinib had a predictable and manageable tolerability profile.
Afatinib. [2018]Afatinib (BIBW 2992, US: GilotrifTM, other countries: Giotrif©) is an irreversible blocker of the ErbB family, acting at the tyrosine kinases of these proteins. In 2013, it was approved by the FDA and the EMA for the treatment of adults with advanced, EGFR mutation-positive non-small-cell lung cancer. Further investigations for the treatment of many other tumors with afatinib, e.g., HNSCC and breast cancer, are ongoing.
Afatinib: a review of its use in the treatment of advanced non-small cell lung cancer. [2022]Afatinib (Gilotrif™, Giotrif(®)) is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases. Afatinib downregulates ErbB signalling by covalently binding to the kinase domains of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER) 2 and HER4, resulting in irreversible inhibition of tyrosine kinase autophosphorylation; it also inhibits transphosphorylation of HER3. Afatinib is approved as monotherapy for the treatment of EGFR tyrosine kinase inhibitor (TKI)-naïve adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutations in the EU, and for the first-line treatment of patients with metastatic NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by a US FDA-approved test in the US. In two randomized, open-label, multinational phase III trials, progression-free survival was significantly prolonged with afatinib compared with pemetrexed plus cisplatin (LUX-Lung 3) or gemcitabine plus cisplatin (LUX-Lung 6) in treatment-naïve patients with advanced NSCLC with activating EGFR mutations. The objective response rate was significantly higher with afatinib than with pemetrexed plus cisplatin or gemcitabine plus cisplatin, and patient-reported outcomes for symptoms such as cough and dyspnoea and certain health-related quality of life measures significantly favoured afatinib versus pemetrexed plus cisplatin or gemcitabine plus cisplatin. Afatinib also showed efficacy in EGFR TKI-naïve patients with advanced lung adenocarcinoma and activating EGFR mutations who had received no more than one prior chemotherapy regimen for advanced disease, according to the results of the noncomparative, multinational, phase II LUX-Lung 2 trial. Oral afatinib had a manageable tolerability profile. EGFR-mediated adverse events (e.g. diarrhoea, rash/acne) were generally managed using dose reduction and delays. In conclusion, afatinib is a valuable new option for use in treatment-naïve or EGFR TKI-naïve patients with advanced lung adenocarcinoma and activating EGFR mutations.
Efficacy of afatinib in a HER2 amplification-positive endometrioid adenocarcinoma patient- a case report. [2020]Afatinib has improved the prognosis of epidermal growth factor receptor-positive advanced non-small cell lung cancer and has been explored in the treatment of human epidermal growth factor receptor 2 (HER2)-amplified breast cancer. However, its clinical efficacy in HER2-amplified endometrial cancer has not been reported. Herein, we present the clinical benefit of afatinib in a case of stage IIIC endometrioid adenocarcinoma refractory to multiple lines of chemotherapy and eventually developed pulmonary, abdominal and pelvic metastasis. Upon referral to our clinic, capture-based targeted sequencing was performed on both blood and tumor samples and revealed HER2 amplification. The patient was administered with afatinib and achieved partial response (PR) after two months of treatment, reflected by a significant reduction in pulmonary lesions and serum levels of tumor markers including carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, 125, 15-3 and cytokeratin 19 fragment antigen 21-1 (CY211). The patient passed away after 3 months of afatinib treatment due to suspected complications of severe intestinal obstruction. Our report demonstrates the efficacy of afatinib in a heavily pre-treated HER2-amplified endometrial cancer patient with multi-organ metastasis. This case also highlights the need to include comprehensive mutational profiling in the standard management of endometrial cancer patients for treatment guidance.
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]Patients presenting with advanced, recurrent, or metastatic endometrial cancer have limited treatment options. On behalf of the Gynecologic Oncology Group, we conducted this phase II trial of nintedanib (BIBF 1120), a potent small molecule triple receptor tyrosine kinase inhibitor of PDGFR α and β, FGFR 1/3, and VEGFR 1-3, in this population.
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]On October 24, 2019, a marketing authorization valid through the European Union (EU) was issued for gilteritinib monotherapy for adult patients who have relapsed or refractory acute myeloid leukemia (AML) with an Fms-like tyrosine kinase 3 (FLT3) mutation. Gilteritinib inhibits FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3 internal tandem duplication (ITD), FLT3 D835Y, and FLT3 ITD D835Y, and it induced apoptosis in leukemic cells expressing FLT3 ITD. The recommended starting dose of gilteritinib is 120 mg (three 40 mg tablets) once daily. Gilteritinib was evaluated in one, phase III, open-label, multicenter, randomized study of gilteritinib (n = 247, gilteritinib arm) versus salvage chemotherapy (n = 124, salvage chemotherapy arm) in patients with relapsed or refractory AML with FLT3 mutation. Overall survival (OS) was statistically significantly different between the two groups with a median OS of 9.3 months in the gilteritinib arm compared with 5.6 months for salvage chemotherapy (hazard ratio, 0.637; 95% confidence interval, 0.490-0.830; p = .0004 one-sided log-rank test). The most common adverse reactions with gilteritinib treatment were blood creatine phosphokinase increase, alanine aminotransferase increase, aspartate aminotransferase increase, blood alkaline phosphatase increase, diarrhea, fatigue, nausea, constipation, cough, peripheral edema, dyspnea, dizziness, hypotension, pain in extremity, asthenia, arthralgia, and myalgia. The objective of this article is to summarize the scientific review of the application leading to regulatory approval in the EU. IMPLICATIONS FOR PRACTICE: Xospata was approved in the European Union as monotherapy for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an Fms-like tyrosine kinase 3 (FLT3) mutation. Gilteritinib resulted in a clinically meaningful and statistically significant improvement of overall survival compared with salvage chemotherapy. At the time of the marketing authorization of gilteritinib, there were no approved standard therapies specifically for adult patients diagnosed with relapsed or refractory AML with FLT3 mutation. In terms of safety, the overall accepted safety profile was considered manageable.
Severe Gastrointestinal Toxicity Following the Use of Gilteritinib: A Case Series and Analysis of Postmarketing Surveillance Data. [2023]Gilteritinib has been approved as monotherapy in adults with acute myeloid leukemia (AML) FLT3 mutated with relapsed or refractory disease, in light of its advantages in terms of survival and the favorable safety profile. Hepatobiliary disorders and musculoskeletal and connective tissue disorders represent the most frequent adverse reactions associated with gilteritinib, whereas the most frequent serious adverse reaction is acute kidney injury. In the summary of product characteristics, gastrointestinal (GI) events are indicated as very common, in particular diarrhea, nausea and stypsis. Furthermore, serious GI disorders have been observed with gilteritinib in clinical trials, including GI hemorrhage, GI perforation and GI obstruction. However, the association with the FLT3 inhibitor has not been confirmed. Nevertheless, serious GI AEs have been recognized as an important potential risk to be monitored in postmarketing surveillance. We present three cases of serious self-limiting GI events observed in patients on gilteritinib treatment for AML, and an analysis of relevant available postmarketing surveillance data.