Combining afatinib and palbociclib for previously treated advanced esophageal squamous cell carcinoma

A Phase 1b/2 Trial of Afatinib Plus Palbociclib in Previously Treated Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

This trial tests whether taking afatinib together with palbociclib helps control tumor growth in people with recurrent or metastatic esophageal squamous cell carcinoma who have already received prior treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: West China Hospital (Academic / other)
• Drugs / interventions: Afatinib
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT06753747 on ClinicalTrials.gov

What this trial studies

This is a Phase 1/2, single-center trial that first determines the safe and tolerable dose of afatinib when given with a fixed 100 mg palbociclib schedule (three weeks on, one week off). After a Phase 1 dose-finding stage, Phase 2 enrolls patients whose tumors show EGFR overexpression or amplification to measure tumor response rates. Key outcomes are safety and tolerability in Phase 1 and objective tumor response and disease control in Phase 2. Eligible patients are adults (18–75) with recurrent or metastatic esophageal squamous cell carcinoma who have progressed after prior therapy and have good performance status.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18–75 with histologically confirmed recurrent or metastatic esophageal squamous cell carcinoma who progressed after prior therapy, have ECOG 0–1, adequate organ function, and (for Phase 2) EGFR overexpression or amplification.

Not a fit: Patients without EGFR overexpression/amplification, those with poor performance status or inadequate organ function, or those unable to travel to the single study site are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could offer a new targeted, oral treatment option that improves tumor control for patients with EGFR-overexpressing esophageal squamous cell carcinoma.

How similar studies have performed: Combining EGFR inhibitors with CDK4/6 inhibitors is largely experimental in esophageal squamous cell carcinoma with supportive preclinical rationale and some early-phase signals in other cancers, but it is not yet proven in ESCC.

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.

Where this trial is running

Chengdu, Sichuan

• West China Hospital — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Jin Zhou — West China Hospital
• Study coordinator: Jin Zhou

Conditions Esophagus Cancer