Study to Evaluate the Efficacy of Afatinib in Skull Base Chordoma

An Open-label, Single-arm, Interventional Clinical Study to Evaluate the Efficacy of Afatinib in Skull Base Chordoma

This is a single arm, open label, single center, and prospective, interventional study to explore clinical efficacy of afatinib in patients with chordoma of skull base. Subject meeting the inclusion criteria will take afatinib (40 mg daily) orally, 4 weeks for a cycle. The primary objective is to assess the efficacy of afatinib in chordoma of skull base by objective response rate (ORR). The Secondary objectives is to assess progression free survival (PFS), overall survival (OS), tumor response duration and tumor shrinkage degree in patients with chordoma of skull base after using afatinib; to evaluate the safety and tolerability of afatinib in patients with chordoma of skull base.

Study Overview

• Status: Not yet recruiting
• Conditions: Chordoma of Clivus
• Intervention / Treatment: Drug: Afatinib

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qilin Zhang, MD; Phone Number: 86-21-52889999; Email: zhangqlhuashan@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Huashan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of 18 years and above;
• Patients with pathologically proven EGFR and/or HER2 expressing relapsed or residual chordoma of skull base, inappropriate or unwilling to receive surgery or radiotherapy;
• Adequate bone marrow function (Hb ≥ 6.0 mmol/L, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥ 75 x 109/L);
• An adequate renal function with GFR ≥ 45 ml/min calculated by Cockroft-Gault formula;
• Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ 3 times ULN;
• Ability to swallow medication;
• Able to understand and provide written informed consent prior to any study procedures.

Exclusion Criteria:

• Life expectancy of less than 3 months;
• Known hypersensitivity to afatinib;
• Major surgery less than 4 weeks prior to start of the study;
• Patients who once participated in other clinical trials within 14 days before the initiation of the study;
• Systemic anti-cancer therapy within 28 days prior to start of the study;
• No tumor progression after radiation therapy prior to start of the study;
• History or presence of serious cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of ≥ 3, unstable angina or poorly controlled arrhythmia, and myocardial infarction within 6 months prior to inclusion;
• Known pre-existing interstitial lung disease;
• No response after 2-week active treatment for known CTCAE Grade 3 or Grade 2 rash/acne;
• Any history or presence of poorly controlled gastrointestinal disorders that may worsen after administration and could affect the absorption of the study drug (e.g. diarrhea, Crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption);
• Active hepatitis B infection (HepB sAg and/ or Hep B DNA positive), active hepatitis C infection (Hep C RNA positive), active tuberculosis and/or known HIV carrier;
• Using other drugs that may influence afatinib and cannot be discontinued during the study, including but not limited to:
• Potent P-gp inhibitors: including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir and amiodarone);
• Potent P-gp inducers: including but not limited to rifampin, carbamazepine, phenytoin, phenobarbital or St. John's wort).
• Pregnant or lactating women;
• Other invasive malignancies diagnosed within the last 5 years (except non-melanoma skin cancer and localized cured prostate and cervical cancer);
• Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afatinib; Subject meeting the inclusion criteria will take afatinib (40 mg daily) orally, 4 weeks for a cycle.	Drug: Afatinib; Subjects will receive evaluations at the beginning of treatment, after every three cycles and at the end of the whole study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Proportion of patients with reduction in tumor volume to a predefined value for a minimum period. Generally, ORR is defined as the sum of complete response and partial response. The best response, that is, the best response throughout the study, will be evaluated.	12 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	duration from the date of inclusion until the date of objective tumor progression or death.	12 months after enrollment
Overall survival	duration from the date of inclusion until the date of death.	12 months after enrollment
Duration of response	duration of partial response and complete response, that is, duration from effective date to the date of proved tumor progression.	12 months after enrollment

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): June 30, 2025
• Study Completion (Anticipated): December 30, 2025

Study Registration Dates

• First Submitted: August 26, 2022
• First Submitted That Met QC Criteria: August 26, 2022
• First Posted (Actual): August 29, 2022

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Chordoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: KY2019-610

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No