NCT06794645

Pembrolizumab and Pemetrexed for Progressive Chordoma

A Phase II Study of Pembrolizumab and High-Dose Pemetrexed for the Treatment of Patients With Progressive Chordoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 21 (estimated)
• Sponsor: Saint John's Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Primary Objective: 1\. To determine objective response rate (ORR) according to RECIST v1.1 of pembrolizumab and high-dose pemetrexed in the treatment of patients with chordoma until disease progression. The OOR will be investigator assessed. Secondary Objectives: 1. To describe the adverse events associated with administering pembrolizumab and high-dose pemetrexed combination treatment. 2. To determine disease control rate based on imaging and overall survival. 3. To determine median PFS and PFS rates at 6, 9, 12, and 18 months. 4. To evaluate changes in volumetric tumor measurements based on imaging. 5. To determine the effects of combination treatment on quality of life, assessed by the EORTC-QLQ-C30 questionnaire. 6. To assess tumor evolution over time in patients with chordoma based on imaging, and molecular profiling. 7. To assess the pharmacodynamic effects of treatment in blood. Exploratory Objective: 1\. To explore the relationship between molecular phenotype and patient response.

Detailed description

This purpose of this study is to test the effectiveness and safety of the research study drug combination of pembrolizumab and high-dose pemetrexed. Both drugs are approved by the U.S. Food and Drug Administration (FDA) for many different types of cancer but is considered investigational because it is not approved by the FDA for use in patients with a rare type of cancer called chordoma. Pembrolizumab (Keytruda) is approved for use in more than ten types of cancer. Pemetrexed (Alimta) is approved for use in patients with certain types of lung cancer called non-squamous non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma. Pemetrexed is also approved for use with pembrolizumab and cisplatin or carboplatin for certain non-squamous NSCLC. The approved dose of pemetrexed is 500 mg/m2, but this study is evaluating a higher dose (900 mg/m2) in effort to deliver more drug to chordoma. Outcome measures will be monitored until disease progression, through study completion (estimated average of 2 years), or withdrawal from study. Chordoma tumors can occur anywhere along the spine, from the head to the tailbone, and surgery and radiation therapy are currently used as treatment for chordoma. There are no drugs at this time that are approved for treating this cancer type. This study is being done to determine how the combination treatment regimen of pembrolizumab and high-dose pemetrexed might affect the growth of chordoma and to learn more about this regimen's safety in patients with chordoma.

Conditions

• Chordomas
• Chordoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day treatment cycle
DRUG	Pemetrexed Phase 2	pemetrexed 900 mg/m2 IV on Day 1 of each 21-day treatment cycle and supportive medications (folic acid, vitamin B12, and dexamethasone).

Timeline

• Start date: 2025-01-01
• Primary completion: 2026-11-30
• Completion: 2026-11-30
• First posted: 2025-01-27
• Last updated: 2025-01-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study