Pancreatic Cancer
Conditions
Keywords
pancreatic cancer, adenocarcinoma of the pancreas (PDAC), mixed adenocarcinoma of the pancreas, locally advanced, recurrent, metastatic
Brief summary
This Phase Ib dose escalation study will evaluate BTH1704, a monoclonal antibody that targets an aberrantly glycosylated antigen Mucin 1, and Imprime PGG, a glucan contained in yeast that is essential in triggering a leukocyte-mediated cytotoxic response towards tumor cells, in combination with gemcitabine in patients with advanced PDAC. The three intravenous drugs are taken in tandem 4 times in a 28-day cycle. The MAD of BTH1704 (BTH, 3 dose levels) in combination with gemcitabine (Gem) and Imprime PGG (I) will be determined using a standard 3+3 design. Treatment continues until disease progression, unacceptable toxicity, physician discretion, or patient refusal.
Interventions
DRUGBTH1704
BTH1704 at assigned doses administered on days 1, 8, 15, and 22 of a 28-day (4 week) cycle.
DRUGIMPRIME PGG
Imprime PGG at assigned doses administered on days 1, 8, 15, and 22 of a 28-day (4 week) cycle.
DRUGGemcitabine
Gemcitabine on days 1, 8, and 15, at assigned doses, of a 28-day (4 week) cycle.
Sponsors
HiberCell, Inc.
University of Illinois at Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female ≥ 18 years 2. Histologically or cytologically confirmed adenocarcinoma of the pancreas, including pancreatic adenosquamous carcinoma, pancreatic anaplastic adenocarcinoma, pancreatic signet ring carcinoma, papillary mucinous carcinoma, acinar cell carcinoma, and ampulla of vater carcinoma,that is locally advanced (not able to proceed with surgery), recurrent, or metastatic (mixed adenocarcinoma of the pancreas is acceptable where the invasive component is predominantly adenocarcinoma) 3. Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1 4. Has an ECOG PS of 0, 1, or 2 5. Has been off chemotherapy for \> or = 2 weeks 6. Has a patent biliary stent if required for biliary ductal obstruction, has adequate nutritional intake, and pain which is stable for a minimum of 24 hrs (pain score ≤ 3/10) 7. Has total bilirubin \< 2 mg/dL, AST and ALT \< 3.0 × ULN or \< 5 x ULN for subjects with known hepatic metastases 8. Has serum creatinine \< 2.5 × ULN 9. Has hemoglobin ≥ 9 g/dL, ANC ≥ 1.0 × 10\^9/L, and platelet count ≥ 100 × 10\^9/L 10. Must be willing and able to comply with study 11. Has read, understood and signed the ICF 12. Women of childbearing potential must not be pregnant or breast-feeding. In addition, a medically acceptable method of birth control must be used or total abstinence. Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP. 13. Men who are not surgically or medically sterile must agree to use an acceptable method of contraception. Male patients with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms at least 30 days after the last dose of study drug. Total abstinence is an acceptable alternative. 14. Prior systemic treatments for metastatic disease are permitted, including targeted therapies, biologic response modifiers, chemotherapy, hormonal therapy, or investigational therapy. 15. Availability of tissue if applicable (from the primary tumor or metastases)for banking 16. Willingness to donate blood for biomarker studies 17. Must have received at least one prior systemic chemotherapy on which disease progressed
Exclusion criteria
1. Has a diagnosis of resectable pancreatic adenocarcinoma 2. Had surgery within 4 weeks prior to study treatment 3. Has either untreated or symptomatic CNS mets 4. Has a known hypersensitivity to BTH1704, murine proteins, or any component of BTH1704 5. Has a known hypersensitivity to baker's yeast 6. Has had previous exposure to Imprime PGG 7. Has previously received an organ or progenitor/stem cell transplant 8. Has a history of blood clots, pulmonary embolism, or DVT unless controlled by anticoagulant treatment 9. Has a known history of HIV positivity or untreated & uncontrolled hepatitis B or C 10. Has any clinically significant infection 11. Has any other severe, uncontrolled medical condition, including uncontrolled DM or unstable CHF or has a known or suspected allergy to the study drug 12. Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormality that may increase the risk associated with study participation 13. Presence of any non-healing wound, fracture, or ulcer 14. Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance 15. Has any mental or medical condition that prevents the patient from giving informed consent 16. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to gemcitabine or drugs to formulate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Up to 30 days post last dose | The primary objective of this Phase 1b study is to determine the maximal administered dose (MAD) of BTH1704 (Mucin-1 targeted antibody) in combination with gemcitabine and Imprime PGG (beta 1,3/1,6 glucan) when given to patients with advanced and previously treated pancreatic ductal adenocarcinoma (PDAC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Effects | Up to 30 days post final dose | Characterize adverse effects (AE) of I-BTH-Gem in patients with advanced PDAC in the second and third line setting. |
| Disease Response based on RECIST Criteria | Up to 8 weeks following final dose. | Evaluate clinical response of I-BTH-Gem in patients with advanced PDAC in the second and third line setting (RECIST v 1.1). |
Countries
United States
Outcome results
None listed