A Phase 1b/2 Trial of Afatinib Plus Palbociclib in Previously Treated Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Palbociclib
- Conditions
- Esophagus Cancer
- Sponsor
- West China Hospital
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Afatinib
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
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?
Investigators
Xingchen Peng
professor
West China Hospital
Eligibility Criteria
Inclusion Criteria
- •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-
- •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:
Exclusion Criteria
- •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:
Arms & Interventions
Phase 1b: Afatinib(30mg)+Palbociclib
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.
Intervention: Palbociclib
Phase 1b: Afatinib(30mg)+Palbociclib
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.
Intervention: Afatinib(30mg)
Phase 1b: Afatinib(40mg)+Palbociclib
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.
Intervention: Palbociclib
Phase 1b: Afatinib(40mg)+Palbociclib
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.
Intervention: Afatinib(40mg)
Phase 2: Afatinib(RP2D)+Palbociclib
The RP2D of Afatinib determined in phase 1b will be administrated in phase 2
Intervention: Palbociclib
Phase 2: Afatinib(RP2D)+Palbociclib
The RP2D of Afatinib determined in phase 1b will be administrated in phase 2
Intervention: Afatinib(RP2D)
Outcomes
Primary Outcomes
Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Afatinib
Time Frame: from the first dose to within 30 days after the last dose
Objective Response Rate (ORR)
Time Frame: up to 2 years
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
Secondary Outcomes
- 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)