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

Esophagus Squamous Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05865132
• Other study ID #: NCC3628
• Status: Recruiting
• Phase: Phase 2
• Start date: April 6, 2023
• Est. completion date: April 2026

Study information

• Verified date: May 2023
• Source: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 2026
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Esophagus Squamous Cell Carcinoma

Intervention

Drug:
• Palbociclib
120mg/125mg po qd on day 1 to 21, every 28 days
• Afatinib
30mg/40mg po qd on day 1 to 28, every 28 days

Locations

Country	Name	City	State
China	National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
AIPING ZHOU

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	objective response rate	3 years
Secondary	DCR	disease control rate	3 years
Secondary	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
Secondary	OS	overall survival	From date of initiation of treatment to date of death up to 3 years