Trial Title:
PAS-004 in Patients With Advanced Solid Tumors
NCT ID:
NCT06299839
Condition:
RAS Mutation
NF1 Mutation
RAF Mutation
Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Cancer
malignant neoplasms
Advanced Solid Tumors
MAP Kinase Signaling Pathway
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
3+3 dose expansion
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PAS-004
Description:
A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MAPK/ERK
kinase, or MEK) 1/2 inhibitor presented in 1 mg, 4mg, and 10 mg strength capsules,
intended for oral administration once daily.
Arm group label:
PAS-004
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.
Criteria for eligibility:
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 without an existing prior genetic test result or
adequate tumor tissue sample must agree to provide tumor tissue via biopsy (paraffin
section or fresh tissue specimens) that will be sent for analysis to confirm
eligibility.
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 3 weeks of enrollment.
2. Having received chemotherapy, radiotherapy, major surgery, targeted therapy,
immunotherapy, or other antitumor treatment within 21 days of enrollment or five
half-lives of the administered therapy, whichever occurs first.
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 known corrected QT (QTc) interval prolongating medication within 7 days 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 currently active 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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
NEXT Oncology
Address:
City:
Austin
Zip:
78758
Country:
United States
Status:
Recruiting
Contact:
Last name:
Erica Torres
Phone:
210-610-5205
Email:
etorres@nextoncology.com
Facility:
Name:
NEXT Oncology
Address:
City:
Irving
Zip:
75039
Country:
United States
Status:
Recruiting
Contact:
Last name:
Erica Torres
Phone:
210-610-5205
Email:
etorres@nextoncology.com
Facility:
Name:
NEXT Oncology
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Contact:
Last name:
Carmen Gonzalez
Phone:
210-580-9521
Email:
cgonzalez@nextoncology.com
Facility:
Name:
NEXT Oncology
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
Blake Patterson
Phone:
703-783-4505
Email:
BPatterson@nextoncology.com
Facility:
Name:
MBAL Sveta Sofia
Address:
City:
Sofia
Zip:
1404
Country:
Bulgaria
Status:
Not yet recruiting
Contact:
Last name:
Veronika Shopova
Phone:
+359-878-33-4932
Email:
veronika.shopova@arensia-em.com
Investigator:
Last name:
Marchela Koleva
Email:
Principal Investigator
Facility:
Name:
Institute of Oncology Bucharest Prof. Dr. Alexandru Trestioreanu
Address:
City:
Bucharest
Zip:
022328
Country:
Romania
Status:
Not yet recruiting
Contact:
Last name:
Natalia E. Cojocaru
Phone:
+40-783-225-184
Email:
natalia.cojocaru@arensia-em.com
Investigator:
Last name:
Laurentia Nicoleta Gales
Email:
Principal Investigator
Facility:
Name:
Institute of Oncology Prof. Dr. Ion Chiricuta
Address:
City:
Cluj-Napoca
Zip:
RO-400015
Country:
Romania
Status:
Not yet recruiting
Contact:
Last name:
Simona Mihaila
Phone:
+40-711-902-882
Email:
simona.mihaila@arensia-em.com
Investigator:
Last name:
Tudor Eliade Ciuleanu
Email:
Principal Investigator
Start date:
February 29, 2024
Completion date:
February 2027
Lead sponsor:
Agency:
Pasithea Therapeutics Corp.
Agency class:
Industry
Source:
Pasithea Therapeutics Corp.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06299839
