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PAS-004 in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06299839
Recruitment Status : Recruiting
First Posted : March 8, 2024
Last Update Posted : March 8, 2024
Sponsor:
Information provided by (Responsible Party):
Pasithea Therapeutics Corp.

Brief Summary:

The main purpose of this clinical trial is to test PAS-004 in people with advanced solid tumors with rat sarcoma virus (RAS), neurofibromatosis type I (NF1), or rapidly accelerated fibrosarcoma (RAF) mutations. The main questions it aims to answer are:

  • How well participants are able tolerate different doses of PAS-004, and
  • What side effects PAS-004 might have.

Study participants will have regular visits to the study doctor and be asked to have tests and exams done to check on their health and safety. Everyone participating in the study will take PAS-004 by mouth as a single dose, followed by one week observation, then once a day during the study, in 28-day cycles. Participants will continue on daily PAS-004 for up to 2 years, or until:

  • They decide to withdraw from the study, or
  • They experience unacceptable side effects, or
  • Their disease progresses, or another illness interferes with taking the study drug, or
  • The sponsors stops the study.

Condition or disease Intervention/treatment Phase
RAS Mutation NF1 Mutation RAF Mutation Advanced Solid Tumors Drug: PAS-004 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 dose expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PAS-004, a MEK (1/2) Inhibitor, in Patients With MAPK Pathway-driven Advanced Solid Tumors With a Documented RAS, NF1, or RAF Mutation or Patients Who Have Failed BRAF/MEK Inhibition
Actual Study Start Date : February 29, 2024
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : February 2027


Arm Intervention/treatment
Experimental: PAS-004
Sequential dose escalation: 2 mg, 4 mg, 6 mg, 9 mg, 12 mg, 15 mg, and 18 mg
Drug: PAS-004
A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MAPK/ERK kinase, or MEK) 1/2 inhibitor presented in 1 mg and 10 mg strength capsules, intended for oral administration once daily.




Primary Outcome Measures :
  1. Evaluation of dose limiting toxicities (DLTs) [ Time Frame: Day 1 through Day 35 (Cycle 1) ]
    Pre-defined DLTs will be assessed for dose escalation and expansion determinations.

  2. Evaluation of adverse events (AEs) [ Time Frame: Screening through Day 1 through Day 35 (Cycle 1), and 30 days after discontinuation of study drug ]
    The number and severity of AEs will be evaluated for dosing cohorts to inform dose escalation and expansion decisions, and support selection of a preliminary recommended phase 2 dose (RP2D).

  3. Evaluation of AEs leading to discontinuation of investigational product (IP), PAS-004. [ Time Frame: Screening through Day 1 through Day 35 (Cycle 1), and 30 days after discontinuation of study drug ]
    The number and severity of AEs leading to discontinuation of study drug will be evaluated for dosing cohorts to inform dose escalation and expansion decisions, and support selection of a preliminary recommended phase 2 dose (RP2D).

  4. Evaluation of hematology laboratory parameters [ Time Frame: Screening through Day 1 through Day 35 (Cycle 1), and 30 days after discontinuation of study drug ]
    Lab parameters will be evaluated for to assess the safety profile of the study drug, and support selection of a preliminary recommended phase 2 dose (RP2D).

  5. Evaluation of clinical chemistry laboratory parameters [ Time Frame: Screening through Day 1 through Day 35 (Cycle 1), and 30 days after discontinuation of study drug ]
    Lab parameters will be evaluated for to assess the safety profile of the study drug, and support selection of a preliminary recommended phase 2 dose (RP2D).


Secondary Outcome Measures :
  1. Apparent terminal elimination half-life (t1/2) in Plasma [ Time Frame: Cycle 1: Day 1 and Day 22 (predose, and 30 min, 1 hr, 2 hr, 3 hr, 5 hr, 8 hr and 24 hr post-dose), Day 4, 8, 15, 29 and 35 (predose) ]
  2. Peak Plasma Concentration (Cmax) [ Time Frame: Cycle 1: Day 1 and Day 22 (predose, and 30 min, 1 hr, 2 hr, 3 hr, 5 hr, 8 hr and 24 hr post-dose), Day 4, 8, 15, 29 and 35 (predose) ]
  3. Plasma predose or trough concentration (Ctau/Ctrough) [ Time Frame: Cycle 1: Day 22 (predose, and 30 min, 1 hr, 2 hr, 3 hr, 5 hr, 8 hr and 24 hr post-dose), Day 8, 15, 29 and 35 (predose) ]
  4. Time of maximum plasma concentration (Tmax) [ Time Frame: Cycle 1: Day 1 and Day 22 (predose, and 30 min, 1 hr, 2 hr, 3 hr, 5 hr, 8 hr and 24 hr post-dose), Day 4, 8, 15, 29 and 35 (predose) ]
  5. Area under the concentration versus time curve from time zero to the last sampling time with quantifiable analyte (AUC0-t) [ Time Frame: Cycle 1: Day 1 (predose, and 30 min, 1 hr, 2 hr, 3 hr, 5 hr, 8 hr and 24 hr post-dose), Day 4 ]
  6. Area under the concentration versus time curve from time zero extrapolated to infinity if possible (AUC0-∞) [ Time Frame: Cycle 1: Day 1 (predose, and 30 min, 1 hr, 2 hr, 3 hr, 5 hr, 8 hr and 24 hr post-dose), Day 4 ]
  7. Area under the concentration versus time curve for the dosing interval, assuming steady state has been reached and duplicating the predose concentration for the 24 hour postdose concentration (AUC0-tau) [ Time Frame: Cycle 1: Day 22 (predose, and 30 min, 1 hr, 2 hr, 3 hr, 5 hr, 8 hr and 24 hr post-dose), Day 8, 15, 29 and 35 (predose) ]
  8. Apparent total plasma clearance if possible (CL/F) [ Time Frame: Cycle 1: Day 1 (predose, and 30 min, 1 hr, 2 hr, 3 hr, 5 hr, 8 hr and 24 hr post-dose), Day 4, and 8 (predose) ]
  9. Evaluation of the percentage of extracellular signal-regulated kinase phosphorylation (pERK) inhibition from baseline [ Time Frame: Day 1 through Day 35 (Cycle 1) ]
  10. Evaluation of the objective response rate (ORR) [ Time Frame: Screening, Day 35 (Cycle 1), and every 9 weeks thereafter ]
    The proportion of participants achieving a partial response (PR) or complete response (CR) per response evaluation criteria in solid tumors (RECIST) 1.1 criteria.

  11. Evaluation of progression-free survival (PFS) [ Time Frame: Cycle 1 Day 1 to date of death, up to 25 months from last participant enrolled ]
    The time from first dose of IP to the date of documented disease progression or date of death due to any cause (whichever occurs first).

  12. Evaluation of overall survival (OS) [ Time Frame: Cycle 1 Day 1 to date of death, up to 13 months from last participant enrolled ]
    The time from first dose of IP to the date of death due to any cause.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Capable of giving signed informed consent which includes compliance with the requirements, prohibitions and restrictions listed in the informed consent form (ICF).
  2. Patient has been informed both verbally and in writing about the objectives of the clinical study, the methods, the anticipated benefits, the potential risks, and the discomfort to which they may be exposed and has given written consent to participation in the study prior to study start and any study-related procedure.
  3. Patient must be at least 18 years of age at the time of signing the ICF.
  4. Patient must be able to swallow oral medication.
  5. Patient with histologically or cytologically diagnosed mitogen-activated protein kinase (MAPK) pathway driven advanced solid tumors with all of the following characteristics:

    1. Tumor cannot be surgically resected
    2. Patient has failed or is ineligible for standard of care therapy
    3. Patient has no available treatment options with known clinical benefit
    4. Documented evidence of rat sarcoma virus (RAS), neurofibromatosis type I (NF1), and/or rapidly accelerated fibrosarcoma (RAF) mutations. Patients with RAF mutations must have previously failed v-Raf murine sarcoma viral oncogene homolog B (BRAF) / MEK inhibition.
  6. Prior to enrollment, patients must agree to provide tumor tissue via biopsy (paraffin section or fresh tissue specimens) that will be sent for analysis to confirm eligibility, if no genetic test data or an adequate tumor tissue sample is available from within the 12 months prior to ICF signature.
  7. Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix B).
  8. Patient must have an estimated life expectancy of at least 12 weeks in the opinion of the Investigator at the time of informed consent.
  9. Patient must have adequate organ function at screening as indicated by the following laboratory value ranges:

    1. Serum total bilirubin ≤ 1.5 × upper limit normal (ULN) (Serum total bilirubin can be ≤ 3.0 × ULN if patients have hemolysis or congenital hemolytic diseases)
    2. Aspartate aminotransferase (AST) ≤ 2.5 × ULN or 5 × ULN for patient with liver metastases
    3. Alanine aminotransferase (ALT) ≤ 2.5 × ULN or 5 × ULN for patient with liver metastases
    4. Albumin ≥2 mg/dL
    5. Creatinine clearance ≥ 45 mL/min (as calculated per Cockcroft-Gault)
    6. Absolute neutrophil count (ANC) ≥ 1.5×109/L
    7. Platelets ≥ 100×109/L
    8. Hemoglobin ≥ 90 g/L (Note: Criteria must be met without a transfusion within 2 weeks of obtaining the sample)
  10. Patient must agree to maintain abstinence (no heterosexual intercourse) or use a highly effective form of contraception during study treatment and for at least 90 days after the last dose of IP. Male patients must agree not to donate sperm while receiving IP and for at least 90 days after the last dose of IP.

Exclusion Criteria:

  1. Participation in another therapeutic clinical trial within 4 weeks of enrollment.
  2. Having received chemotherapy, radiotherapy, major surgery, targeted therapy, immunotherapy, or other antitumor treatment within 4 weeks of enrollment.
  3. Known or active central nervous system metastases.

    1. Patients with untreated brain metastases ≤ 30 mm that are asymptomatic, do not have significant edema, and do not require steroids or anti-seizure medications are eligible after discussion with the Medical Monitor.
    2. Patients with previously treated brain metastases may participate provided they are stable after treatment and without evidence of progression by imaging for at least 4 weeks prior to the first dose of IP administration and are not using corticosteroids for at least 7 days prior to IP administration.
    3. Patients with confirmed leptomeningeal disease are to be excluded.
  4. Unresolved toxicity from prior antitumor therapy defined as AEs > Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, except for alopecia; neurotoxicity AEs of patients who have received prior chemotherapy needs to be restored to Grade 2 or below. Patients with ≥ Grade 3 bleeding within 4 weeks of first study treatment dose should be excluded.
  5. Taken a medication that is a strong cytochrome P450 (CYP3A) inhibitor or inducer within 14 days of initiation of study therapy dosing.
  6. Taken a corrected QT (QTc) interval prolongating medication within 7days of initiation or longer if the half-life of the QTc prolonging medication is such that the drug is not cleared from the body within 7 days (5 half-lives) of initiation of study therapy dosing.
  7. Active dysphagia, digestive system disease, malabsorption syndrome, or other conditions affecting PAS-004 absorption.
  8. Previous or current retinal vein stenosis, retinal detachment, central retinal vein occlusion, or glaucoma.
  9. Active interstitial pneumonia, including clinically significant radiation pneumonitis.
  10. Impaired cardiac function or cardiac disease as indicated by:

    1. Average QTc interval > 470 ms as calculated according to the QTc formula of the instrument at the research center where electrocardiogram (ECG) measurements are performed.
    2. Grade ≥ 3 congestive heart failure per New York Heart Association (NYHA) guidelines.
    3. Clinically significant arrhythmias, including but not limited to, complete left bundle branch conduction abnormalities and 2nd degree atrioventricular block.
  11. Pregnant or lactating female patients.
  12. Known allergy or hypersensitivity to the investigational product (IP), including excipients, or history of severe adverse reaction to any drug, or sensitivity to components of the IP.
  13. Clinically active bacterial, fungal, or viral infections, hepatitis B (hepatitis B virus surface antigen positive and hepatitis B virus DNA over 1000 IU/ml) or hepatitis C (hepatitis C virus RNA positive), human immunodeficiency virus infection (HIV positive).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06299839


Locations
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United States, Texas
NEXT Oncology Recruiting
Austin, Texas, United States, 78758
Contact: Erica Torres    210-610-5205    etorres@nextoncology.com   
NEXT Oncology Recruiting
Irving, Texas, United States, 75039
Contact: Erica Torres    210-610-5205    etorres@nextoncology.com   
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Carmen Gonzalez    210-580-9521    cgonzalez@nextoncology.com   
United States, Virginia
NEXT Oncology Recruiting
Fairfax, Virginia, United States, 22031
Contact: Blake Patterson    703-783-4505    BPatterson@nextoncology.com   
Sponsors and Collaborators
Pasithea Therapeutics Corp.
Investigators
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Study Director: Graeme Currie, PhD Pasithea Therapeutics Corp.
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Responsible Party: Pasithea Therapeutics Corp.
ClinicalTrials.gov Identifier: NCT06299839    
Other Study ID Numbers: PAS-004-102
2024-510900-34 ( EudraCT Number )
First Posted: March 8, 2024    Key Record Dates
Last Update Posted: March 8, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pasithea Therapeutics Corp.:
Cancer
malignant neoplasms
Advanced Solid Tumors
MAP Kinase Signaling Pathway
Additional relevant MeSH terms:
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Neoplasms