Trial Title:
A Study of OT-101 With mFOLFIRINOX in Patients With Advanced and Unresectable or Metastatic Pancreatic Cancer
NCT ID:
NCT06079346
Condition:
Pancreatic Ductal Adenocarcinoma
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
OT-101
Description:
OT-101: antisense oligodeoxynucleotide complementary to the messenger ribonucleic acid
(mRNA) of the human TGF-β2 gene
Arm group label:
OT-101 + mFOLFIRINOX
Intervention type:
Drug
Intervention name:
mFOLFIRINOX
Description:
Folinic acid, 5-FU, Irinotecan, Oxaliplatin
Arm group label:
OT-101 + mFOLFIRINOX
Arm group label:
mFOLFIRINOX Only
Summary:
The goal of this clinical study is to compare the efficacy and safety of OT-101 in
combination with mFOLFIRINOX (folinic acid, 5-FU, irinotecan, oxaliplatin) to mFOLFIRINOX
alone in patients with advanced and unresectable or metastatic pancreatic cancer.
Detailed description:
OT-01-P201 is designed as a randomized, open-label, active controlled, multicenter Phase
2B/Phase 3 study designed to compare the efficacy and safety of OT-101 in combination
with modified FOLFIRINOX (folinic acid, 5-FU, irinotecan, oxaliplatin) to modified
FOLFIRINOX alone in patients with advanced and unresectable or metastatic pancreatic
cancer. The primary endpoint of the study is overall survival and key secondary endpoints
are progression-free survival and objective response rate.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. A diagnosis of advanced and unresectable or metastatic pancreatic adenocarcinoma
confirmed by:
1. Histopathology from primary tumor in pancreas, OR
2. Histopathology from a non-pancreatic lesion in the presence of a mass in the
pancreas consistent with pancreatic adenocarcinoma or a medically documented
history of pancreatic adenocarcinoma.
2. Measurable disease per RECIST v.1.1
3. Male or non-pregnant, non-lactating female, ≥18 years or age
1. If a female patient is of child-bearing potential, as evidenced by menstrual
periods, she must have a negative serum pregnancy test (beta-human chorionic
gonadotropin [β- hCG]) documented prior to the first administration of stud
drugs
2. Female patients of childbearing age and women < 12 months since the onset of
menopause must agree to use acceptable contraceptive methods for the duration
of the study and 9 months following the last injection of OT-101.
3. Male patients must use effective contraception for a duration of 6 months after
the final dose, as per the prescribing information for oxaliplatin.
4. Provide signed written informed consent
5. Eastern Cooperative Group (ECOG) Performance Status (PS) score of 0-1
6. Willingness and ability to comply with study requirements
7. Patient has adequate organ function by the following laboratory assessments at
baseline(obtained ≤28 days prior to Randomization):
Hematologic
- Platelets ≥100×109/L
- Hemoglobin ≥9.0 g/dL
- Absolute Neutrophil Count (ANC) ≥1.5×109/L
- Patient has acceptable coagulation values obtained ≤28 days prior to
Randomization as demonstrated by prothrombin time (PT) or international
normalized ratio (INR) and partial thromboplastin time (PTT) ≤1.5× upper limit
of normal (ULN) (if on Coumadin, patient must be changed to LMWH or on Factor
II or Xa anticoagulant with a t½ of less than 24 hours
Hepatic
- Aspartate transaminase (AST)/alanine transaminase (ALT) ≤3×ULN (if liver
metastases are present, ≤5×ULN)
- Alkaline phosphatase ≤2.0×ULN (if liver metastases are present, ≤5×ULN)
- Total bilirubin ≤2.0×ULN (in patients with Gilbert's Syndrome total bilirubin <
or = 2.5xULN)
Renal
- Calculated creatinine clearance ≥50 mL/min. Actual body weight should be used
for calculating creatinine clearance (e.g., using the Modification of Diet in
Renal Disease [MDRD] formula. For patients with a body mass index (BMI) >30
kg/m2, lean body weight should be used instead
8. Patient must have a life expectancy of ≥3 months in the opinion of the Investigator
Exclusion Criteria:
1. Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma
(ie,lymphoma, sarcoma), adenocarcinoma originating from the biliary tree, or
cystadenocarcinoma
2. Patient has experienced a decrease in ECOG PS between Screening visit and within 72
hours prior to Randomization
3. Patient on Coumadin and not willing to change to LMWH or oral Factor II or Xa
inhibitor with t½ of less than 24 hours
4. History of prior malignancy, except for adequately treated in situ cancer, basal
cell, squamous cell skin cancer, or other cancers (eg, breast and prostate) for
which the patient has been disease-free for at least 3 years. Patients with prior
cancer that is adequately controlled per the judgement of the Investigator will not
be excluded from the study
5. Any serious medical condition, laboratory abnormality, psychiatric illness, or
comorbidity that, in the judgment of the Investigator, would make the patient
inappropriate for the study
6. Patients with abnormal electrocardiogram (ECG) at baseline (QT or QTc interval >470
ms) will be excluded from this study. The eligibility of patients with ventricular
pacemakers for whom the QT interval may not be accurately measurable will be
determined on a case-by-case basis by the Sponsor's medical representative in
consultation with the principal investigator.
7. Serious systemic fungal, bacterial, viral, or other infection that is not controlled
or requires intravenous antibiotics
8. Known history of positivity (regardless of immune status) for human immunodeficiency
virus(HIV)
9. Known history of chronic active or active viral hepatitis A, B, or C infection
10. Clinically significant bleeding within 2 weeks prior to Randomization (eg,
gastrointestinal[GI] bleeding or intracranial hemorrhage)
11. Pregnant or lactating women
12. Myocardial infarction, coronary bypass surgery, or arterial thromboembolic events
within the last 6 months prior to Randomization, symptomatic congestive heart
failure (New York Heart Association Classification >Class II, unstable angina, or
unstable cardiac arrhythmia requiring medication
13. Clinically significant ascites defined as requiring ≥1 paracentesis every 2 weeks
14. Major surgery, defined as any surgical procedure that involves general anesthesia
and a significant incision (ie, larger than what is required for placement of
central venous access, percutaneous feeding tube, or biopsy) within 28 days prior to
Randomization or anticipated surgery during the study period
15. Prior history of receiving immune checkpoint inhibitors (anti-CTLA4, anti-PD1,
anti-PD-L1)
16. Peripheral neuropathy (>Grade 1)
17. Known history of dihydropyrimidine dehydrogenase deficiency (DPD) -
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the
catabolism of 5-fluorouracil (5-FU). Thus, patients with a DPD deficiency are at
risk of developing severe 5-FU-associated toxicity
18. History or risk of autoimmune disease, including but not limited to systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
associated with antiphospholipid syndrome, Wegner´s granulomatosis, Sjogren´s
syndrome, Bell´s palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or
glomerulonephritis, except for psoriasis not requiring systemic therapy, vitiligo or
alopecia areata, or hypothyroidism
19. Patients receiving any of the following medications are not eligible for study:
1. Investigational agents other than the protocol drugs
2. Anti-coagulants (except for heparin to maintain the patency of central venous
catheters)
3. Non-steroidal anti-inflammatory drugs
4. Clopidogrel (Plavix), dipyridamole (Persantine), or any other drug that
inhibits platelet functions
5. Patients on greater than 2 mg dexamethasone, 10 mg Prednisone or or equivalent
dose in alternate corticosteroid daily or actively undergoing corticosteroid
dose escalation are NOT eligible
20. History of allergic reactions or known hypersensitivity to compounds of similar
chemical or biologic composition to OT-101 such as anti-sense oligonucleotides or
siRNA
21. Patients who are unable to return for follow-up visits or obtain follow-up studies
required to assess toxicity to therapy. Telemedicine visits are acceptable
22. Not willing and able to comply with study requirements including protocol mandated
procedures and visits
23. Other contraindications as defined in the product label of the components of the
mFOLFIRINOX treatment regimen
24. Participation in another investigational clinical trial within 30 days of receiving
the last dose of investigational study drug
25. Clinically significant psychiatric disorders, legal incapacity or limited legal
capacity
26. Patients with a primary immunodeficiency
27. Patients with active central nervous system (CNS) metastases. (Patients with
adequately treated CNS metastases who are clinically stable for at least 6 weeks
after discontinuation of corticosteroids may be eligible for enrollment with the
approval of the Sponsor's medical representative and the principal investigator)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Karmanos Cancer Center
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Anthony Shields, MD
Email:
Principal Investigator
Facility:
Name:
Baylor College of Medicine
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shalini Makawita, MD
Start date:
May 1, 2024
Completion date:
June 1, 2027
Lead sponsor:
Agency:
Oncotelic Inc.
Agency class:
Industry
Source:
Mateon Therapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06079346
