Overview

ProAgio in Pancreatic Ductal Adenocarcinoma (PDAC)

Status:
Recruiting
Trial end date:
2025-10-01
Target enrollment:
0
Participant gender:
All
Summary
This is an open-label Phase I/Ib dose-escalation, dose-expansion clinical trial of the safety, pharmacokinetics and clinical activity of ProAgio combined with gemcitabine and nab paclitaxel (G-nP) in previously untreated subjects with metastatic pancreatic ductal adenocarcinoma (PDAC)
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
ProDa BioTech, LLC
Collaborators:
Georgia State University
University of Alabama at Birmingham
Treatments:
Gemcitabine
Paclitaxel
Criteria
Inclusion Criteria:

1. Must be ≥ 18 years of age on day of signing informed consent.

2. Histologic or cytologic diagnosis of pancreatic adenocarcinoma with clinical stage IV.

3. In the dose escalation phase: patients must be eligible for gemcitabine and nab
paclitaxel. For dose expansion phase: patients must have received 5FU-based therapy
for metastatic disease or for neoadjuvant/adjuvant therapy in prior 12 months.

4. Presence of a lesion that can be safely biopsied for correlative assays.

5. Patient must meet the following laboratory values at the screening visit:

- Absolute Neutrophil Count ≥1.5 x 10'9/L

- Platelets ≥100 x 10'9/L

- Hemoglobin (Hgb) ≥9 g/dL

- Serum creatinine <1.5 mg/dL OR Creatinine Clearance ≥60 mL/min using
Cockcroft-Gault formula

- Total bilirubin ≤1.5 x ULN

- Aspartate transaminase (AST) ≤2.5 x ULN, except for subjects with liver
metastasis, who may only be included if AST ≤5.0 x ULN

- Alanine transaminase (ALT) ≤2.5 x ULN, except for subjects with liver metastasis,
who may only be included if ALT ≤5.0 x ULN

6. Presence of measurable disease by RECIST 1.1 criteria

7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
(Appendix A: Performance Status Criteria).

8. Written informed consent must be obtained prior to any screening procedures.

9. Normal ECG defined as the following: QTcF at screening <450 ms (male subjects), <460
ms (female subjects)

10. Before enrollment, a woman must be either:

1. Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea
for at least 12 months or any age with amenorrhea for at least 6 months and a
serum follicle stimulating hormone (FSH) level >40 IU/mL); permanently sterilized
(eg, tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be
incapable of pregnancy.

2. Of childbearing potential and practicing (during the study and for 6 months after
receiving the last dose of study agent) a highly effective method of birth
control consistent with local regulations regarding the use of birth control
methods for subjects participating in clinical studies: eg, established use of
oral, injected or implanted hormonal methods of contraception; placement of an
intrauterine device (IUD) or intrauterine system (IUS); barrier methods; true
abstinence (when this is in line with the preferred and usual lifestyle of the
subject).

3. Note: If the childbearing potential changes after start of the study (eg, woman
who is not heterosexually active becomes active) a woman must begin a highly
effective method of birth control, as described above.

11. A woman of childbearing potential must have a negative serum (β-human chorionic
gonadotropin [β-hCG]) or urine pregnancy test at screening.

12. During the study and for 6 months after receiving the last dose of study agent, a
woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction.

13. A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control eg, either condom with
spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men
must also not donate sperm during the study and for 3 months after receiving the last
dose of study drug.

14. Sign an informed consent document indicating that they understand the purpose of and
procedures required for the study, are willing to participate in the study, and are
willing and able to adhere to the prohibitions and restrictions specified in this
protocol.

Informed consent must be obtained before performing any study specific procedures.

Exclusion Criteria:

1. Prior exposure to gemcitabine and nab paclitaxel

2. Clinically significant peripheral neuropathy

3. Any untreated central nervous system (CNS) lesion. However, subjects are eligible if:

a) all known CNS lesions have been treated with radiotherapy or surgery and b) patient
remained without evidence of CNS disease progression ≥4 weeks after treatment.

4. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GMCSF, M-CSF),
thrombopoietin mimetics or erythroid stimulating agents ≤ 2 weeks prior start of study
treatment. If erythroid stimulating agents were initiated more than 2 weeks prior to
the first dose of study treatment and the patient is on a stable dose, they can be
maintained.

5. Active unstable autoimmune disease. Documented history of autoimmune disease that is
well controlled on stable immune suppressive therapy can be enrolled after discussion
with principal investigator.

6. Allogenic bone marrow or solid organ transplant.

7. Known history or current interstitial lung disease or non-infectious pneumonitis.

8. Malignant disease, other than that being treated in this study. Exceptions to this
exclusion include the following: malignancies that were treated curatively and have
not recurred within 2 years prior to study treatment; completely resected basal cell
and squamous cell skin cancers and any completely resected carcinoma in situ.

9. Clinically significant infection, including known HIV or hepatitis C infection, or
known hepatitis B surface antigen positivity. Testing of asymptomatic patients will
not be required.

10. Clinically significant ongoing infection.

11. Received an investigational drug (including investigational vaccines) or used an
invasive investigational medical device within 14 days or 5 half-lives before
enrollment or is currently enrolled in the treatment stage of an investigational
study.

12. A woman who is pregnant or breast-feeding, or a woman who is planning to become
pregnant or a man who plans to father a child while enrolled in this study or within
30 days after the last dose of study agent.

13. Had hospitalization for infection or major surgery (eg, requiring general anesthesia)
within 2 weeks before enrollment or have not fully recovered from surgery. Note:
subjects with surgical procedures conducted under local anesthesia may participate.

14. History or current diagnosis of cardiac disease indicating significant risk of safety
for subjects participating in the study such as uncontrolled or significant cardiac
disease, including any of the following:

1. recent myocardial infarction (within last 6 months),

2. uncontrolled congestive heart failure,

3. unstable angina (within last 6 months),

4. clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained
ventricular tachycardia, and clinically significant second or third degree AV
block without a pacemaker).