RECRUITING

Pembrolizumab and Pemetrexed for Progressive Chordoma

Conditions

Chordomas Chordoma Pembrolizumab Pemetrexed High-Dose Pemetrexed

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2025-01

Study Completion:2026-11-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06794645

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participant has the ability to understand and the willingness to provide a signed and dated informed consent form. 2. Participant has the willingness to comply with all study procedures and availability for the duration of the study. 3. Participant has a pathologic diagnosis of chordoma. 4. Evidence of progressive disease within the past six months before study entry, according to RECIST v1.1. 5. Participant has measurable disease, according to RECIST v1.1. 6. Participant is male or female, ≥ 18 years of age. 7. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at study entry: 1. 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). 2. 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. 3. In bed \>50% of the time. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.- 4. 100% bedridden. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5. Dead. 8. Participant has adequate organ function: 1. ANC ≥ 1.5 x 109/L 2. Platelets ≥ 100 x 109/L 3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L Note: Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. 4. Total bilirubin ≤ 1.5 x ULN Note: Patients with Gilbert's syndrome with a total bilirubin ≤ 2.0 ULN and direct bilirubin within normal limits are permitted. 5. ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN in presence of known hepatic metastasis) 6. Serum creatinine ≤ 1.5 x ULN 9. Participant has the ability to interrupt non-steroidal anti-inflammatory drugs (NSAIDS) 2 days before (5 days for long-acting NSAIDs), the day of, and for 2 days following administration of Pemetrexed. 10. Participant has the ability to take folic acid, Vitamin B12, and dexamethasone according to the protocol schedule. 11. Participant has recovered from any previous therapy-related toxicity to CTCAE Grade 1 or to their clinical baseline at study entry. 12. Criteria for known Hepatitis B and C positive participant: Hepatitis B screening tests are required. 12.1 Hepatitis B positive participants • Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to study intervention. * Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. 12.2 Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. * Participants must have completed curative anti-viral therapy at least 4 weeks prior to study intervention 13. Male participant: agrees to use highly effective contraception as detailed in Section 4.3.2 of this protocol during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period. 14. Female participant: meets at least one of the following conditions:	4.2 PARTICIPANT EXCLUSION CRITERIA 1. Participant has insufficient time from prior therapy to the first dose of study treatment: 1. Less than 4 weeks for an investigational agent or investigational device 2. Less than 3 weeks for major surgery 3. Less than 2 weeks for radiation therapy 4. Less than 3 weeks for a cytotoxic agent 5. Less than 2 weeks or 5 half-lives, whichever is shorter, for a targeted therapy (e.g. tyrosine kinase inhibitor) 6. Less than 3 weeks or 5 half-lives, whichever is shorter, for an antibody-based therapy 2. Participant has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. 3. 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. 4. 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). 5. Participant has an active bacterial infection requiring intravenous \[IV\] antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection. 6. Participant has a known history of non-infectious pneumonitis or currently has pneumonitis. 7. Participant has a known history of human immunodeficiency virus (HIV) infection. 8. Participant has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) or Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. 9. Participant has had an allogenic tissue/solid organ transplant. 10. Participant has third space fluid which cannot be controlled by drainage. Note: For patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing. However, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy. 11. Participant has a severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study intervention, including, but not limited to: 1. Uncontrolled diabetes; 2. Renal disease that requires dialysis; 3. Pulmonary disorder requiring supplemental oxygen to keep saturation \>95% and the situation is not expected to resolve within 2 weeks; 4. Severe dyspnea at rest or requiring oxygen therapy; 5. Interstitial lung disease; 6. History of major surgical resection involving the stomach or small bowel; 7. Preexisting Crohn's disease; 8. Ulcerative colitis; 9. Uncontrolled vasculitis and/or disease with known vasculitis; 10. Preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea; 11. Psychiatric illness, substance abuse, or other social situation that would interfere with cooperation with the requirements of the trial. 12. Participant has a personal history or presence of any of the following cardiovascular conditions: 1. Syncope of cardiovascular etiology; 2. Ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation); 3. Myocardial infraction within 6 months of investigational product administration; 4. Unstable angina; 5. Sudden cardiac arrest; 6. Congestive heart failure (NYHA classification ≥ 3): 13. Participant has a known additional malignancy that is progressing or has required active treatment with the past 3 years. 14. Participant is a woman of childbearing potential (WOCBP) who is pregnant or nursing. 15. Participant has a history of severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients (L-histidine, polysorbate 80, or sucrose).

Inclusion Criteria

Exclusion Criteria

1. Participant has the ability to understand and the willingness to provide a signed and dated informed consent form.
2. Participant has the willingness to comply with all study procedures and availability for the duration of the study.
3. Participant has a pathologic diagnosis of chordoma.
4. Evidence of progressive disease within the past six months before study entry, according to RECIST v1.1.
5. Participant has measurable disease, according to RECIST v1.1.
6. Participant is male or female, ≥ 18 years of age.
7. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at study entry:
1. 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).
2. 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.
3. In bed \>50% of the time. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.-
4. 100% bedridden. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
5. Dead.
8. Participant has adequate organ function:
1. ANC ≥ 1.5 x 109/L
2. Platelets ≥ 100 x 109/L
3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L Note: Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
4. Total bilirubin ≤ 1.5 x ULN Note: Patients with Gilbert's syndrome with a total bilirubin ≤ 2.0 ULN and direct bilirubin within normal limits are permitted.
5. ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN in presence of known hepatic metastasis)
6. Serum creatinine ≤ 1.5 x ULN 9. Participant has the ability to interrupt non-steroidal anti-inflammatory drugs (NSAIDS) 2 days before (5 days for long-acting NSAIDs), the day of, and for 2 days following administration of Pemetrexed.
10. Participant has the ability to take folic acid, Vitamin B12, and dexamethasone according to the protocol schedule.
11. Participant has recovered from any previous therapy-related toxicity to CTCAE Grade 1 or to their clinical baseline at study entry.
12. Criteria for known Hepatitis B and C positive participant: Hepatitis B screening tests are required.
12.1 Hepatitis B positive participants • Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to study intervention.
* Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
12.2 Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
* Participants must have completed curative anti-viral therapy at least 4 weeks prior to study intervention 13. Male participant: agrees to use highly effective contraception as detailed in Section 4.3.2 of this protocol during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period.
14. Female participant: meets at least one of the following conditions:

4.2 PARTICIPANT EXCLUSION CRITERIA
1. Participant has insufficient time from prior therapy to the first dose of study treatment:
1. Less than 4 weeks for an investigational agent or investigational device
2. Less than 3 weeks for major surgery
3. Less than 2 weeks for radiation therapy
4. Less than 3 weeks for a cytotoxic agent
5. Less than 2 weeks or 5 half-lives, whichever is shorter, for a targeted therapy (e.g. tyrosine kinase inhibitor)
6. Less than 3 weeks or 5 half-lives, whichever is shorter, for an antibody-based therapy
2. Participant has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention.
3. 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.
4. 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).
5. Participant has an active bacterial infection requiring intravenous \[IV\] antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection.
6. Participant has a known history of non-infectious pneumonitis or currently has pneumonitis.
7. Participant has a known history of human immunodeficiency virus (HIV) infection.
8. Participant has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) or Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
9. Participant has had an allogenic tissue/solid organ transplant.
10. Participant has third space fluid which cannot be controlled by drainage. Note: For patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing. However, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy.
11. Participant has a severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study intervention, including, but not limited to:
1. Uncontrolled diabetes;
2. Renal disease that requires dialysis;
3. Pulmonary disorder requiring supplemental oxygen to keep saturation \>95% and the situation is not expected to resolve within 2 weeks;
4. Severe dyspnea at rest or requiring oxygen therapy;
5. Interstitial lung disease;
6. History of major surgical resection involving the stomach or small bowel;
7. Preexisting Crohn's disease;
8. Ulcerative colitis;
9. Uncontrolled vasculitis and/or disease with known vasculitis;
10. Preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea;
11. Psychiatric illness, substance abuse, or other social situation that would interfere with cooperation with the requirements of the trial.
12. Participant has a personal history or presence of any of the following cardiovascular conditions:
1. Syncope of cardiovascular etiology;
2. Ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation);
3. Myocardial infraction within 6 months of investigational product administration;
4. Unstable angina;
5. Sudden cardiac arrest;
6. Congestive heart failure (NYHA classification ≥ 3):
13. Participant has a known additional malignancy that is progressing or has required active treatment with the past 3 years.
14. Participant is a woman of childbearing potential (WOCBP) who is pregnant or nursing.
15. Participant has a history of severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients (L-histidine, polysorbate 80, or sucrose).

Contacts and Locations

Study Contact

Naveed Wagle, MD

CONTACT

310-829-8265

Naveed.Wagle@providence.org

Akanksha Sharma, MD

CONTACT

310-582-7640

akanksha.sharma@providence.org

Study Locations (Sites)

Providence Saint John's Health Center

Santa Monica, California, 90404

United States

Collaborators and Investigators

Sponsor: Saint John's Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-01

Study Completion Date2026-11-30

Study Record Updates

Study Start Date2025-01

Study Completion Date2026-11-30

Terms related to this study

Keywords Provided by Researchers

Pembrolizumab
Pemetrexed
High-Dose Pemetrexed

Additional Relevant MeSH Terms

Chordomas
Chordoma