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

NCT06753747 | Recruiting Phase 1

• 1 other identifier: 2024-143
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if Afatinib plus Palbociclib works in previously treated recurrent or metastatic esophageal squamous cell carcinoma. It will also learn about the safety of the combination of Afatinib and Palbociclib. The main questions it aims to answer are: What is the safe and tolerable dose of Afatinib when combined with 100 mg of Palbociclib (administered orally, three weeks on and one week off)? Does the combination therapy of Afatinib and Palbociclib induce a tumor response in patients with recurrent or metastatic esophageal squamous cell carcinoma who have received prior treatments?

Conditions

Esophagus Cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Afatinib

  from the first dose to within 30 days after the last dose

• Objective Response Rate (ORR)

  the proportion of patients with a confirmed complete response or partial response, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  up to 2 years

Secondary Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events

  from the first dose to within 30 days after the last dose

• Disease Control Rate (DCR)

  up to 2 years

• Progression free survival

  up to 2 years

• Overall survival(OS)

  up to 2 years

• Anti-tumor activity by Duration of Response (DOR)

  up to 2 years

Study Arms (3)

Phase 1b: Afatinib(30mg)+Palbociclib

EXPERIMENTAL

In phase 1b, there is 2 dose levels for Afatinib, 30mg qd and 40 mg qd, and if no patients experience DLT on 30mg level, 40mg level will be administered.

Drug: Palbociclib; Drug: Afatinib(30mg)

Phase 1b: Afatinib(40mg)+Palbociclib

EXPERIMENTAL

In phase 1b, there is 2 dose levels for Afatinib, 30mg qd and 40 mg qd, and if no patients experience DLT on 30mg level, 40mg level will be administered.

Drug: Palbociclib; Drug: Afatinib(40mg)

Phase 2: Afatinib(RP2D)+Palbociclib

EXPERIMENTAL

The RP2D of Afatinib determined in phase 1b will be administrated in phase 2

Drug: Palbociclib; Drug: Afatinib(RP2D)

Interventions

Palbociclib DRUG

Palbociclib will be given at a dose of 100 mg every day orally with three weeks on and one week off. Four weeks is a cycle.

Phase 1b: Afatinib(30mg)+Palbociclib; Phase 1b: Afatinib(40mg)+Palbociclib; Phase 2: Afatinib(RP2D)+Palbociclib

Afatinib(30mg) DRUG

Afatinib will be administered orally at a dose of 30 mg once daily (QD) in each 4-week cycle.

Phase 1b: Afatinib(30mg)+Palbociclib

Afatinib(40mg) DRUG

Afatinib will be administered orally at a dose of 40 mg once daily (QD) in each 4-week cycle.

Phase 1b: Afatinib(40mg)+Palbociclib

Afatinib(RP2D) DRUG

In the Phase 2 study, the recommended Phase 2 dose (RP2D) of Afatinib, determined during the Phase 1b portion, will be utilized.

Phase 2: Afatinib(RP2D)+Palbociclib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Hemoglobin (Hb) ≥ 90 g/L;
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
• Platelet count (PLT) ≥ 75 × 10⁹/L.
• Serum biochemistry:
• Total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal (ULN);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for patients with liver metastases, ALT and AST ≤ 5 × ULN;
• 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.

You may not qualify if:

• 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:
• Prior use of EGFR inhibitors or CDK4/6 inhibitors.
• Administration of any live vaccines (e.g., influenza or varicella vaccines) within 4 weeks before the first dose or during the study.
• Major surgery or significant trauma within 4 weeks before the first dose.
• 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:
• NYHA Class II or higher heart failure.
• Ischemic heart disease (e.g., myocardial infarction or angina).
• Clinically significant supraventricular or ventricular arrhythmias.
• Poorly controlled diabetes (fasting blood glucose ≥ 10 mmol/L).
• Poorly controlled hypertension (systolic BP \> 150 mmHg and/or diastolic BP \> 100 mmHg).

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital

Chengdu, Sichuan, 610041, China

RECRUITING

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

palbociclib; Afatinib

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jin Zhou

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Zhou

CONTACT

+86-13880626596; zhoujin096@scu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: December 23, 2024
• First Posted: December 31, 2024
• Study Start: September 10, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)