A Trial of the Combination of Afatinib and Palbociclib in Previously Treated Advanced Esophageal Squamous Cell Carcinoma

Launched by WEST CHINA HOSPITAL · Dec 23, 2024

Keywords

ClinConnect Summary

This clinical trial is exploring the use of two medications, Afatinib and Palbociclib, to see if they can help patients with advanced esophageal squamous cell carcinoma (a type of throat cancer) who have already been treated before. The main goals are to find out the safest dose of Afatinib to use with Palbociclib and to see if this combination can shrink tumors in patients whose cancer has come back or spread.

To participate in this trial, patients must be between 18 and 75 years old and have a confirmed diagnosis of advanced esophageal squamous cell carcinoma that has not responded to previous treatments. They should also meet certain health criteria, such as having good organ function and not having other serious medical conditions. If eligible, participants will take these medications in a specific schedule (three weeks on, one week off) and will be closely monitored for safety and effectiveness throughout the study. This trial is not yet recruiting, so patients interested in participating will need to wait until it officially begins.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age between 18 and 75 years
• • Histologically or cytologically confirmed as ESCC, locally advanced and unresectable, with local recurrence (local lymph node metastases) or distant metastases
• • Immunohistochemistry confirmed EGFR(3+) or EGFR-FISH-amplification or next generation sequencing confirmed EGFR-amplification (EGFR expression is not required in Phase 1b, but only patients with EGFR overexpression will be included in Phase 2).
• • Disease progression after first-line or subsequent lines of therapy.
• • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• * Adequate organ function within 7 days prior to treatment initiation, meeting the following criteria:Hematology (without transfusion, blood products, or administration of G-CSF or other hematopoietic stimulants within the past 14 days):
• • 1. Hemoglobin (Hb) ≥ 90 g/L;
• • 2. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
• • 3. Platelet count (PLT) ≥ 75 × 10⁹/L.
• Serum biochemistry:
• • 1. Total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal (ULN);
• • 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for patients with liver metastases, ALT and AST ≤ 5 × ULN;
• • 3. Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 60 mL/min. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%, as assessed by Doppler ultrasound.
• • Coagulation: International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN.
• • Female patients of childbearing potential must agree to use appropriate contraception from screening until 3 months after the end of treatment and must not be breastfeeding. A negative pregnancy test is required within 7 days before the start of treatment. Male patients must agree to use appropriate contraception or have undergone surgical sterilization during the study and for 8 weeks after the last administration of study medication.
• • All subjects are recruited on a voluntary basis and sign the informed consent. They are required to be compliant with the study and cooperative with the follow-up.
• Exclusion Criteria:
• • Patients who have a history of other malignancies in the past five years (except for the cured basal cell carcinoma and cervical carcinoma in situ)
• • The patient has any active autoimmune disease or a history of autoimmune disease
• • History of severe allergic reactions or known allergies to macromolecular protein preparations, Afatinib, Palbociclib, or any component of their formulations that have resulted in hospitalization.
• • Presence of contraindications to Palbociclib or Afatinib.
• * Previous or planned treatments as follows:
• • 1. Prior use of EGFR inhibitors or CDK4/6 inhibitors.
• • 2. Administration of any live vaccines (e.g., influenza or varicella vaccines) within 4 weeks before the first dose or during the study.
• • 3. Major surgery or significant trauma within 4 weeks before the first dose.
• • 4. Residual toxicities from prior anti-tumor therapies not resolved to ≤ Grade 1 per CTCAE v5.0, except for alopecia or platinum-based therapy-induced neuropathy.
• * Severe medical conditions, such as:
• • 1. NYHA Class II or higher heart failure.
• • 2. Ischemic heart disease (e.g., myocardial infarction or angina).
• • 3. Clinically significant supraventricular or ventricular arrhythmias.
• • 4. Poorly controlled diabetes (fasting blood glucose ≥ 10 mmol/L).
• • 5. Poorly controlled hypertension (systolic BP \> 150 mmHg and/or diastolic BP \> 100 mmHg).
• • 6. Left ventricular ejection fraction (LVEF) \< 50% on echocardiography.
• • 7. QTc interval \> 450 ms in males or \> 470 ms in females.
• • 8. Abnormal ECG findings deemed to pose additional risk by the investigator.
• • Active infections or unexplained fever within 48 hours prior to the first dose, or systemic antibiotic use within one week prior to informed consent.
• • Active hepatitis B (HBV DNA ≥ 2000 IU/mL or ≥ 10⁴ copies/mL), hepatitis C (anti-HCV antibody positive with detectable HCV RNA), known HIV positivity, or acquired immunodeficiency syndrome (AIDS).
• • Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.
• • Pregnancy or lactation.
• • Receipt of any investigational drug within 4 weeks before the first dose or concurrent enrollment in another clinical trial, except for observational (non-interventional) studies or interventional trials in follow-up.
• • Any other factors deemed by the investigator to potentially interfere with study participation, including the ability to complete study treatment and follow-up.