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

AIPING ZHOU

Status and phase: Enrolling; Phase 2

Conditions: Esophagus Squamous Cell Carcinoma

Treatments: Drug: Palbociclib; Drug: Afatinib

Study type: Interventional

Funder types: Other

Identifiers

NCT05865132

NCC3628

Details and patient eligibility

About

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).

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Palbociclib + Afatinib

Experimental group

Description:

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.

Treatment:

Drug: Afatinib

Drug: Palbociclib