Pemetrexed for the Treatment of Chordoma

NCT ID: NCT03955042

Last Updated: 2023-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-06
• Study Completion Date: 2023-01-18

Brief Summary

The purpose of this study is to test the safety and tolerability of pemetrexed administered to people with chordoma. Other purposes of this study are to:

• find out side effects (good and bad) of pemetrexed;
• learn more about how pemetrexed might affect the growth of cancer cells;
• evaluate tumor characteristics by collecting tumor tissue samples if available;
• look at biomarkers (biochemical features that can be used to measure the progress of disease or the effects of a drug) in blood and cerebrospinal fluid if available.

Detailed Description

This is a prospective, open-label, single-arm pilot feasibility study of pemetrexed for the treatment of adult patients with chordoma. All patients providing informed consent will be screened for eligibility. Eligible patients will receive pemetrexed by intravenous infusion on Day 1 of each 21-day treatment cycle, pre-medications (folic acid, vitamin B12, and dexamethasone), and ibuprofen if needed. Patients will continue dosing of pemetrexed until disease progression, unacceptable toxicity, withdrawal of consent, or treating physician determines it is in their best interest to stop. All patients will have regular evaluations for assessment of safety parameters and anti-tumor activity as detailed in the study flow chart.

Conditions

Chordoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pemetrexed

Pemetrexed

Group Type: EXPERIMENTAL

Pemetrexed

Intervention Type: DRUG

Pemetrexed 900 mg/m\^2 on Day 1 of each 21-day cycle. Supportive medications of ibuprofen, folic acid, vitamin B12, and dexamethasone.

Interventions

Pemetrexed

Pemetrexed 900 mg/m\^2 on Day 1 of each 21-day cycle. Supportive medications of ibuprofen, folic acid, vitamin B12, and dexamethasone.

Intervention Type: DRUG

Other Intervention Names

Alimta

Eligibility Criteria

Inclusion 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 diagnosis of chordoma.

4. Participant is male or female, 18 years of age or older.

5. Participant has a Karnofsky Performance Status of 50% or greater.

6. Participant has adequate organ function:

1. ANC at least 1.5 x 10^9/L or higher

2. Platelets at least 100 x 10^9/L or higher

3. Hemoglobin at least 8 g/dL or higher.

4. Total bilirubin 1.5 x upper limit of normal (ULN) or lower.

5. ALT and AST 3 x ULN or lower.

6. Serum creatinine 1.5 x ULN or lower.

7. 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 2 days following administration of Pemetrexed.

8. Participant has the ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.

9. Participant has recovered from any previous therapy-related toxicity to CTCAE Grade 1 or to their clinical baseline at study entry.

Exclusion Criteria

1. Participant is less than 28 days from any investigational agent.

2. Participant has third space fluid which cannot be controlled by drainage.

3. 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/social situations that would limit compliance with study requirements.

4. Participant has an active bacterial infection requiring intravenous [IV] antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C).

5. 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).

6. Participant is a female of childbearing potential who is pregnant or nursing.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Chordoma Foundation

OTHER

Sponsor Role: collaborator

Saint John's Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Santosh Kesari

Director, Neuro-Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Santosh Kesari, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Saint John's Cancer Institute

Locations

John Wayne Cancer Institute

Santa Monica, California, United States

Countries

United States

References

Kesari S, Wang F, Juarez T, Ashili S, Patro CPK, Carrillo J, Nguyen M, Truong J, Levy J, Sommer J, Freed DM, Xiu J, Takasumi Y, Bouffet E, Gill JM. Activity of pemetrexed in pre-clinical chordoma models and humans. Sci Rep. 2023 May 5;13(1):7317. doi: 10.1038/s41598-023-34404-4.

Reference Type: DERIVED

PMID: 37147496 (View on PubMed)

Other Identifiers

H3E-US-X091

Identifier Type: OTHER

Identifier Source: secondary_id

JWCI-18-0704

Identifier Type: -

Identifier Source: org_study_id