Chordoma Foundation


CDK4/6 inhibition in locally advanced/metastatic chordoma


This is a Phase 2 trial studying the effectiveness of a targeted cancer drug called palbociclib. Palbociclib (Ibrance®) inhibits the proteins CDK4 and CDK6, which are believed to be involved in driving the growth of chordoma tumors. This study is designed specifically for chordoma patients 18 years or older with locally recurrent or metastatic tumors. It is currently open at the National Center for Tumor Diseases (NCT) in Heidelberg, the University of Ulm, and the University of Duisburg-Essen. The principal investigator for this study is Prof. Dr. Stefan Fröhling and the scientific coordinator is Prof. Dr. Richard F. Schlenk, both at NCT.

Why this trial is being done

Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are two proteins which enable tumor growth. These proteins are usually controlled by another protein called p16, which is produced by a gene called CDKN2A. When the CDKN2A gene is lost from tumor cells, p16 is no longer produced and the activity of CDK4 and CDK6 increases, causing cancer cells to multiply out of control.

Drugs that block the activity of the CDK4 and CDK6 proteins, called “CDK4/6 inhibitors”, are approved to treat several different types of cancer. Palbociclib is a CDK4/6 inhibitor that is approved to treat certain types of breast cancer and is currently being tested in other tumor types.

CDK4/6 inhibitors are relevant to chordoma patients because nearly all chordoma tumors have a loss of the CDKN2A gene, and therefore don’t produce the p16 protein to help regulate CDK4 and CDK6. Several CDK4/6 inhibitors, including palbociclib, have been shown to slow or stop the growth of chordoma cell lines and mouse models.

This trial aims to determine whether palbociclib can shrink or stop the growth of chordoma tumors in patients with recurrent or metastatic disease.

Who can participate

This trial is designed specifically for chordoma patients whose tumors 1) have come back in the same area (locally recurrent) or have spread to other parts of the body (metastatic) and 2) have not responded or are no longer responding to treatment with a tyrosine kinase inhibitor such as imatinib or erlotinib. Patients must meet the following criteria to be eligible:

  • Confirmed diagnosis of a chordoma
  • Loss of p16 protein determined by immunohistochemistry OR loss of CDKN2A gene determined by genomic sequencing
  • Presence of CDK4/6 and RB1 proteins determined by immunohistochemistry or RNA testing
  • Recurrent or metastatic disease (cannot be newly diagnosed, primary chordoma)
  • Age 18 years or older
  • No major laboratory abnormalities
  • Willing and able to travel to the enrolling study site for all treatment and follow-up visits

Full eligibility criteria can be found at

How the trial will work

  • Treatment cycles last for 28 days. Participants take a 125 mg oral dose of palbociclib daily for 21 days, followed by a break for 7 days. These cycles continue for a minimum of 6 months unless there is tumor growth, intolerable side effects are experienced, or the participant leaves the trial during this 6-month period.
  • At the end of the initial 6-month period, participants who have received benefit from the treatment will be offered continuation of treatment with agreement between their treating physician and the principal investigator and scientific coordinator.
  • Check-up exams will be performed every 4 weeks and imaging done every 12 weeks.
  • After completion of the treatment, a follow-up period of 6 months is planned with visits to the trial center every 3 months.
  • All exams, treatments, and evaluations are provided at the trial site where the patient enrolled in the study. Participants not local to the trial sites MUST be willing and able to travel to their trial site for all visits required by the trial.

How to enroll in this trial

The trial team will see all potential patients in a clinic visit before beginning the screening process. See the FAQ below, “How do I find out if I’m eligible to participate?”, for more specific information on enrolling.



If you have more questions about this trial or other clinical trials that may be options for chordoma patients, please contact a Chordoma Foundation Patient Navigator at

Contact a CF Patient Navigator

Learn more about targeted therapy


Medical information provided by the Chordoma Foundation in any medium is for informational and educational purposes only. After reading content from the Chordoma Foundation, review the information carefully with your physician. Information from the Chordoma Foundation is not a substitute for consultations with qualified health care professionals who are familiar with your medical conditions and needs. The Chordoma Foundation strongly recommends that care and treatment decisions be made in consultation with your physician or other qualified health care professionals who are familiar with your specific health situation.

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