Clinical Trial: Afatinib in Locally Advanced and Metastatic Chordoma

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase 2, Single Arm, European Multi-center Trial Evaluating the Efficacy of Afatinib as First-line or Later-line Treatment in Advanced Chordoma.

Brief Summary: In this phase 2, single arm trial patients with locally advanced or metastatic, pathologically proven, EGFR expressing chordoma will be treated with afatinib. Two cohorts of patients will be included: 20 first line patients and 20 second or further line patients. The treatment will be given in 4 week cycles until disease progression. Median PFS according to RECIST 1.1 will be evaluated. The objective is to increase the median PFS ≥ 12 months in first-line treatment cohort and ≥ 9 months in later-line treatment cohort. Additional exploratory research will be performed, consisting of a pharmacokinetic study and translational studies on EGFR pathway activation and signalling on blood and tumor samples.

Detailed Summary:
Sponsor: Leiden University Medical Center

Current Primary Outcome:

• Median PFS according to RECIST 1.1 criteria on afatinib treatment (first-line cohort) [ Time Frame: From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year). ]
  The objective is to increase the median PFS ≥ 12 months in first-line treatment cohort.
• Median PFS according to RECIST 1.1 criteria on afatinib treatment (second or later line cohort) [ Time Frame: From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year). ]
  The objective is to increase the median PFS ≥ 9 months in later-line treatment cohort.
• Quality of life assessment by EORTC QLC-30 questionnaire. [ Time Frame: From date of start treatment until date of first documented of progression of withdrawal (through study completion, an average of 1 year). ]
  Change from baseline in EORTC QLC-30 questionnaire score.
• Quality of life assessment by Brief pain inventory short form [ Time Frame: From date of start treatment until date of first documented of progression of withdrawal (through study completion, an average of 1 year). ]
  Change from baseline on Brief pain inventory short form score.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Growth modulation index. [ Time Frame: From date of start treatment until date of first documented of progression (through study completion, an average of 1 year). ]
  Time to progression during afatinib treatment (TTP2) divided by time to progression before start of this treatment TTP1 (= growth modulation index)
• Toxicity [ Time Frame: From date of start treatment until date of first documented of progression or withdrawal (through study completion, an average of 1 year). ]
  Toxicity determined by CTCAE v 4.03 criteria
• Overall survival. [ Time Frame: Survival follow-up after end of treatment every 3 months for up to 2 years followed by contact at 3 years. ]
  Overall survival from start of afatinib treatment

Original Secondary Outcome: Same as current

Information By: Leiden University Medical Center

Dates:
Date Received: February 10, 2017
Date Started: June 2017
Date Completion: December 2019
Last Updated: April 4, 2017
Last Verified: April 2017