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

May 17, 2023 updated by: AIPING ZHOU

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Recruiting
        • National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Palbociclib + Afatinib
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
120mg/125mg po qd on day 1 to 21, every 28 days
Drug: Afatinib
30mg/40mg po qd on day 1 to 28, every 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR
Time Frame: 3 years
objective response rate
3 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AIPING ZHOU

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 6, 2023

Primary Completion (Anticipated)

April 1, 2025

Study Completion (Anticipated)

April 1, 2026

Study Registration Dates

First Submitted

April 11, 2023

First Submitted That Met QC Criteria

May 17, 2023

First Posted (Actual)

May 18, 2023

Study Record Updates

Last Update Posted (Actual)

May 18, 2023

Last Update Submitted That Met QC Criteria

May 17, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCC3628

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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