Palbociclib Combined With Afatinib for Advanced Squamous Carcinoma of Esophagus or Gastroesophageal Junction

Study Overview
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Brief Summary
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This is a prospective, multicenter, exploratory study. Patients with advanced esophageal or gastro-esophageal junction squamous carcinoma who had progressed on first-line chemotherapy combined with immune checkpoint inhibitors were treated with CDK4/6 inhibitor Palbociclib combined with Afatinib. Dose titration was used to determine the final dose, and objective antitumor efficacy was evaluated every 2 cycles (8 weeks +/- 7 days) according to RECIST 1.1 criteria, until tumor progression, intolerable toxicity, death, or withdrawal of informed consent. The primary endpoint is the objective response rate (ORR).

Official Title
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CDK4/6 Inhibitor Palbociclib Combined With Afatinib as Second-line Treatment for Advanced Squamous Carcinoma of the Esophagus or Gastroesophageal Junction Progressed on at Least First-line Chemotherapy: a Phase 2 Trial

Conditions
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Esophagus Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Palbociclib
* Drug: Afatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed metastatic or inoperable locally advanced squamous carcinoma of the esophagus or gastroesophageal junction that is not amenable to radical radiotherapy. Prior progression to at least first-line chemotherapy which must include immune checkpoint inhibitors (except in patients with contraindications to immune checkpoint inhibitors). Adjuvant/neoadjuvant therapy is allowed and is considered first-line therapy for advanced disease if recurrence occurs during or within 6 months of completion of adjuvant/neoadjuvant therapy. At least one measurable tumor lesion according to RECIST V1.1 criteria. A lesion previously treated with radiotherapy is not acceptable as a target lesion unless the lesion is significantly progressive. Sign the informed consent form 18 75 years Performance status: ECOG 0-1 Good organ function: Blood routine: hemoglobin ≥90g/L, neutrophil ≥1.5×10^9/L, platelet ≥100×10^9/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥50ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL; Ejection fraction at least 50% (or lower limit of normal) by echocardiogram Exclusion Criteria: Other pathological category, such as adenocarcinoma, adenosquamous carcinoma Have received CDK4/6 inhibitors or anti-EGFR targeted drugs in the past Known to have allergic reactions to any ingredients or excipients of experimental drugs Unable to swallow or under other circumstance which would drug absorption Other active malignant tumors, excluding those who have been disease free for more than 5 years or in situ cancer considered to have been cured by adequate treatment Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs or hypertension was not controlled, defined as systolic / diastolic blood pressure > 140 / 90 mmHg after antihypertensive drug Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class III or IV congestive heart failure in the past 12 months Known to be infected with human immunodeficiency virus (HIV), have acquired immunodeficiency syndrome (AIDS) related diseases, have active hepatitis B or hepatitis C Pregnant or nursing May increase the risk associated with participation in the study or administration of the study drug or mental illness that may interfere with the interpretation of research results There are other serious diseases that the researchers believe patients cannot be included in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palbociclib + Afatinib<br>The first 6 enrolled patients were treated with Palbociclib 125 mg po qd on day 1 to 21, Afatinib 40 mg po qd on day 1 to 14, every 28 days as a cycle; If there are ≥ 2 cases of dose-limiting toxicity (DLT), the following 6 patients will reduce the dose to Palbociclib 125mg po qd on day 1 to 21, Afatinib 30mg po qd on day 1 to 28, every 28 days as a cycle; If ≥ 2 cases of DLT occur again, the following 6 patients will reduce the dose to Palbociclib 100mg po qd on day 1 to 21, Afatinib 30mg po qd on day 1 to 28, every 28 days as a cycle; If ≥ 2 cases of DLT occur again, we will analyze the characteristics of adverse events and determine the subsequent dose. | Drug: Palbociclib<br>* 120mg/125mg po qd on day 1 to 21, every 28 days<br>Drug: Afatinib<br>* 30mg/40mg po qd on day 1 to 28, every 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | objective response rate | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DCR | disease control rate | 3 years | 
| PFS | progression free survival | From date of initiation of treatment to date of progression or death due to any cause, whichever occurs first up to 3 years | 
| OS | overall survival | From date of initiation of treatment to date of death up to 3 years |