Pembrolizumab and Pemetrexed for Progressive Chordoma

NCT06794645 | Recruiting Phase 2 FDA Drug

• 1 other identifier: SJCI-23-1001
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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. 1.To describe the adverse events associated with administering pembrolizumab and high-dose pemetrexed combination treatment.
2. 2.To determine disease control rate based on imaging and overall survival.
3. 3.To determine median PFS and PFS rates at 6, 9, 12, and 18 months.
4. 4.To evaluate changes in volumetric tumor measurements based on imaging.
5. 5.To determine the effects of combination treatment on quality of life, assessed by the EORTC-QLQ-C30 questionnaire.
6. 6.To assess tumor evolution over time in patients with chordoma based on imaging, and molecular profiling.
7. 7.To assess the pharmacodynamic effects of treatment in blood.

Conditions

Chordomas; Chordoma

Keywords

Pembrolizumab; Pemetrexed; High-Dose Pemetrexed

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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. The OOR will be investigator assessed.

  Day 1 of study treatment until disease progression up to 2 years

Secondary Outcomes (2)

• Adverse Events of Combination Therapy

  From time of 1st Treatment to End of Treatment or Diease Progression for approximately 1 year

• Median progression-free survival

  From time of 1st Treatment to End of Treatment or Disease Progression up to 2 years

Other Outcomes (10)

• Disease Control

  From time of 1st Treatment to End of Treatment or Disease Progression up to 2 years

• PFS at 6 months

  From time of 1st Treatment to six months

• PFS at 9 months

  From time of 1st Treatment to nine months

Study Arms (1)

Single Arm

EXPERIMENTAL

Eligible patients will receive pembrolizumab 200 mg IV infusion on Day 1 of each 21-day cycle, and pemetrexed 900 mg/m2 by intravenous (IV) infusion on Day 1 of each 21-day treatment cycle and supportive medications (folic acid, vitamin B12, and dexamethasone).

Drug: Pembrolizumab; Drug: Pemetrexed Phase 2

Interventions

Pembrolizumab DRUG

pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day treatment cycle

Single Arm

Pemetrexed Phase 2 DRUG

pemetrexed 900 mg/m2 IV on Day 1 of each 21-day treatment cycle and supportive medications (folic acid, vitamin B12, and dexamethasone).

Also known as: High-Dose Pemetrexed

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet the criteria listed below.
• Participant has the ability to understand and the willingness to provide a signed and dated informed consent form.
• Participant has the willingness to comply with all study procedures and availability for the duration of the study.
• Participant has a pathologic diagnosis of chordoma.
• Evidence of progressive disease within the past six months before study entry, according to RECIST v1.1.
• Participant has measurable disease, according to RECIST v1.1.
• Participant is male or female, ≥ 18 years of age.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at study entry:
• ECOG Performance Status Grade Description 0 Normal activity. Fully active, able to carry on all pre-disease performance without restriction.
• Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work).
• In bed \<50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.
• In bed \>50% of the time. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.-
• % bedridden. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
• Dead.
• \. Participant has adequate organ function:

You may not qualify if:

• An individual who meets any of the following appropriate criteria below will be excluded from participation in this study.
• Participant has insufficient time from prior therapy to the first dose of study treatment:
• Less than 4 weeks for an investigational agent or investigational device
• Less than 3 weeks for major surgery
• Less than 2 weeks for radiation therapy
• Less than 3 weeks for a cytotoxic agent
• Less than 2 weeks or 5 half-lives, whichever is shorter, for a targeted therapy (e.g. tyrosine kinase inhibitor)
• Less than 3 weeks or 5 half-lives, whichever is shorter, for an antibody-based therapy
• Participant has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention.
• Note: Please refer to Section 6.4 for information on COVID-19 vaccines.
• Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
• Participant has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Participant has an active bacterial infection requiring intravenous \[IV\] antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection.
• Participant has a known history of non-infectious pneumonitis or currently has pneumonitis.

Sponsors & Collaborators

• Saint John's Cancer Institute: lead
• Chordoma Foundation: collaborator

Study Sites (1)

Providence Saint John's Health Center

Santa Monica, California, 90404, United States

RECRUITING

Related Publications (4)

• Williams NL, Wuthrick EJ, Kim H, Palmer JD, Garg S, Eldredge-Hindy H, Daskalakis C, Feeney KJ, Mastrangelo MJ, Kim LJ, Sato T, Kendra KL, Olencki T, Liebner DA, Farrell CJ, Evans JJ, Judy KD, Andrews DW, Dicker AP, Werner-Wasik M, Shi W. Phase 1 Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases. Int J Radiat Oncol Biol Phys. 2017 Sep 1;99(1):22-30. doi: 10.1016/j.ijrobp.2017.05.028. Epub 2017 May 26.

  PMID: 28816150 BACKGROUND

• Adjei AA. Pemetrexed: a multitargeted antifolate agent with promising activity in solid tumors. Ann Oncol. 2000 Oct;11(10):1335-41. doi: 10.1023/a:1008379101017.

  PMID: 11106124 BACKGROUND

• McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM. Chordoma: incidence and survival patterns in the United States, 1973-1995. Cancer Causes Control. 2001 Jan;12(1):1-11. doi: 10.1023/a:1008947301735.

  PMID: 11227920 BACKGROUND

• Eriksson B, Gunterberg B, Kindblom LG. Chordoma. A clinicopathologic and prognostic study of a Swedish national series. Acta Orthop Scand. 1981 Feb;52(1):49-58. doi: 10.3109/17453678108991758.

  PMID: 7211316 BACKGROUND

MeSH Terms

Conditions

Chordoma

Interventions

pembrolizumab; Pemetrexed

Condition Hierarchy (Ancestors)

Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Central Study Contacts

Naveed Wagle, MD

CONTACT

310-829-8265; Naveed.Wagle@providence.org

Akanksha Sharma, MD

CONTACT

310-582-7640; akanksha.sharma@providence.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Associate Professor of Neurosciences

Model Details: Participants who qualify for the study based upon baseline assessments will have pembrolizumab and pemetrexed administered by intravenous infusion (IV) on Day 1 of each 21-day cycle (every three weeks).

Study Record Dates

• First Submitted: November 21, 2024
• First Posted: January 27, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: January 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)