NCT03110744: NCT-PMO-1601

CDK4/6 Inhibition in Locally Advanced/Metastatic Chordoma

Completed Phase 2 Last updated 27 March 2023

What this trial tests

Phase 2 trial testing Palbociclib in Chordoma in 43 participants. Completed in 22 December 2022.

Timeline

15 December 2017

Primary endpoint
22 December 2022

22 December 2022

Quick facts

Lead sponsor	University Hospital Heidelberg
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	43
Start date	15 December 2017
Primary completion	22 December 2022
Estimated completion	22 December 2022
Sites	3 locations across Germany

Drugs / interventions tested

• Palbociclib (Palbociclib) — full drug profile →

Conditions studied

• Chordoma — all drugs for Chordoma →

Sponsor

University Hospital Heidelberg

Who can join

18 and older, any sex, with Chordoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

In chordoma cell lines and patient biopsies, the p16 (CDKN2A) tumor suppressor is consistently deleted. Thus, chordomas are an example of a tumor with universal activation of the cyclin-dependent kinases 4 and 6 (CDK4/6) pathway, and experiments with patient-derived chordoma cell lines demonstrate aberrant CDK4/6 activity downstream of p16 loss can be efficiently inhibited by the CDK4/6 inhibitor palbociclib, resulting in reduced proliferation and growth of neoplastic cells. The investigators aim to conduct a phase II clinical trial to evaluate the efficacy of the small-molecule CDK4/6 inhibitor palbociclib in patients with locally advanced/metastatic chordoma who are not candidates for standard therapy. The primary objective is disease control in patients with chordoma treated with palbociclib as single agent. The study design of this phase II study is based on a Simon two-stage design.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Selective inhibition of CDK4/6: A safe and effective strategy for developing anticancer drugs.
   Yuan K, Wang X, Dong H, Min W, et al · · 2021 · cited 103× · PMID 33532179 · DOI 10.1016/j.apsb.2020.05.001
2. Chordoma-Current Understanding and Modern Treatment Paradigms.
   Barber SM, Sadrameli SS, Lee JJ, Fridley JS, et al · · 2021 · cited 83× · PMID 33806339 · DOI 10.3390/jcm10051054
3. Defective homologous recombination DNA repair as therapeutic target in advanced chordoma.
   Gröschel S, Hübschmann D, Raimondi F, Horak P, et al · · 2019 · cited 70× · PMID 30967556 · DOI 10.1038/s41467-019-09633-9
4. Molecular Targeted Therapy in the Treatment of Chordoma: A Systematic Review.
   Meng T, Jin J, Jiang C, Huang R, et al · · 2019 · cited 70× · PMID 30775316 · DOI 10.3389/fonc.2019.00030
5. Synergistic drug combinations and machine learning for drug repurposing in chordoma.
   Anderson E, Havener TM, Zorn KM, Foil DH, et al · · 2020 · cited 29× · PMID 32737414 · DOI 10.1038/s41598-020-70026-w
6. NCT/DKFZ MASTER handbook of interpreting whole-genome, transcriptome, and methylome data for precision oncology.
   Mock A, Teleanu MV, Kreutzfeldt S, Heilig CE, et al · · 2023 · cited 22× · PMID 37884744 · DOI 10.1038/s41698-023-00458-w
7. Targeted Therapy for Chordoma: Key Molecular Signaling Pathways and the Role of Multimodal Therapy.
   Akinduro OO, Suarez-Meade P, Garcia D, Brown DA, et al · · 2021 · cited 19× · PMID 33893940 · DOI 10.1007/s11523-021-00814-5
8. The early evolutionary landscape of osteosarcoma provides clues for targeted treatment strategies.
   Kovac M, Ameline B, Ribi S, Kovacova M, et al · · 2021 · cited 16× · PMID 33963544 · DOI 10.1002/path.5699