RECRUITING

ProAgio in Pancreatic Ductal Adenocarcinoma (PDAC)

Conditions

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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, nab-paclitaxel (G-nP) or gemcitabine, nab-paclitaxel (G-nP) and atezolizumab in previously untreated subjects with metastatic pancreatic ductal adenocarcinoma (PDAC)

Official Title

A Phase I/Ib Trial of ProAgio, an Anti- αvβ3 Integrin Cytotoxin, in Combination With Gemcitabine and Nab-paclitaxel or Gemcitabine, Nab-paclitaxel and Atezolizumab for Advanced Pancreatic Cancer

Quick Facts

Study Start:2023-09-14

Study Completion:2028-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06182072

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. 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.	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: 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). 15. Active or prior documented autoimmune or inflammatory disorders (including, but not limited to inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion: * Patients with vitiligo or alopecia * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Patients without active disease in the last 5 years may be included but only after consultation with the study physician * Patients with celiac disease controlled by diet alone * Patients with type I diabetes mellitus who are on an insulin regimen are eligible for the study 16. Current or prior use of immunosuppressive medication ≤ 14 days prior to registration. * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 17. Receipt of live attenuated vaccine ≤30 days prior to registration. Note: Patients, if enrolled, should not receive live vaccine whilst on study treatment and up to 30 days after the last dose of study treatment. 18. History of pneumonitis/interstitial lung disease

Inclusion Criteria

Exclusion 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.
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.

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:
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).
15. Active or prior documented autoimmune or inflammatory disorders (including, but not limited to inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
* Patients with vitiligo or alopecia
* Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
* Any chronic skin condition that does not require systemic therapy
* Patients without active disease in the last 5 years may be included but only after consultation with the study physician
* Patients with celiac disease controlled by diet alone
* Patients with type I diabetes mellitus who are on an insulin regimen are eligible for the study
16. Current or prior use of immunosuppressive medication ≤ 14 days prior to registration.
* Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
17. Receipt of live attenuated vaccine ≤30 days prior to registration. Note: Patients, if enrolled, should not receive live vaccine whilst on study treatment and up to 30 days after the last dose of study treatment.
18. History of pneumonitis/interstitial lung disease

Contacts and Locations

Study Contact

Damon R Michaels

CONTACT

615-614-1185

damon.michaels@medelis.com

Zhi-Ren Lui

CONTACT

zliu8@gsu.edu

Principal Investigator

Mehmet Akce, MD

PRINCIPAL_INVESTIGATOR

The University of Alabama at Birmingham

Study Locations (Sites)

O'Neal Comprehensive Cancer Center, University of Alabama

Birmingham, Alabama, 35294

United States

Collaborators and Investigators

Sponsor: ProDa BioTech, LLC

Mehmet Akce, MD, PRINCIPAL_INVESTIGATOR, The University of Alabama at Birmingham

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-14

Study Completion Date2028-06-30

Study Record Updates

Study Start Date2023-09-14

Study Completion Date2028-06-30

Terms related to this study

Additional Relevant MeSH Terms

Pancreatic Ductal Adenocarcinoma (PDAC)