Study of SBP-101 Combined With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
Primary Purpose
Pancreatic Cancer Metastatic, Pancreatic Cancer Stage IV, Stage IV Pancreatic Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
SBP-101
nab-paclitaxel
Gemcitabine Injection
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer Metastatic
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. Patients with pancreatic acinar cell carcinoma may also be included.
- Is previously untreated for metastatic pancreatic ductal adenocarcinoma, was diagnosed within the past 3 months, and is expected to receive standard treatment with gemcitabine and nab-paclitaxel.
- Measurable disease on CT or MRI scan by RECIST v 1.1 criteria.
- ECOG Performance Status 0 or 1.
- Adult, age ≥ 18 years, male or female.
- Females of child-bearing potential must have a negative serum pregnancy test within 14 days prior to start of study treatment and must use an adequate method of contraception during the study. All sexually active males must also use an adequate method of contraception during the study. Female subjects will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months of consecutive amenorrhea, without other known or suspected cause) and over 55 years old or have been sterilized surgically (i.e., bilateral tubal ligation, hysterectomy or bilateral oophorectomy, all with surgery at least one month before dosing).
Adequate bone marrow, hepatic, renal and coagulation function as defined by the following:
- Absolute neutrophil count ≥1.5 x 109/L
- Hemoglobin ≥9.0 g/dL (90 g/L)
- Platelets ≥100 x 109/L
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) (if no hepatic metastases). If hepatic tumor involvement, AST and ALT ≤5 x ULN.
- Bilirubin ≤1.5 x ULN
- Prothrombin time (PT) / international normalized ratio (INR) ≤1.5 x ULN if not on anti-coagulants
- Calculated creatinine clearance >50 mL/min using the Cockcroft and Gault equation
- QTc interval ≤ 470 msec at Baseline.
- Life expectancy ≥ 3 months.
- Willing and able to provide written informed consent: voluntary agreement to participate in the study following disclosure of risks and procedures required, including possibility of onset of exocrine pancreatic insufficiency with subsequent requirement for life-long pancreatic enzyme replacement.
Exclusion Criteria:
- Evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the opinion of the Investigator or Medical Monitor, makes it undesirable for the subject to participate in the study or that would jeopardize compliance with the protocol. Subjects with pre-existing well-controlled diabetes are not excluded.
- Medical or psychiatric conditions that compromise the subject's ability to give informed consent or to complete the protocol or a history of non-compliance
- Presence of islet-cell or pancreatic neuroendocrine tumor or mixed adenocarcinoma-neuroendocrine carcinoma
- Have symptomatic central nervous system (CNS) malignancy or metastasis. Screening of asymptomatic subjects without history of CNS metastases is not required.
- Serum albumin <30 g/L (3.0 g/dL)
- Evidence of deep vein thrombosis or pulmonary embolism or other thromboembolic event during screening
- Presence of known active bacterial, fungal, or viral infection requiring systemic therapy
- Known active infection with human immunodeficiency virus (HIV), hepatitis B or C
- Presence of interstitial lung disease, pulmonary fibrosis, or pulmonary hypersensitivity reaction
- Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV
- Maldigestion/malabsorption syndrome pre-dating the diagnosis of pancreatic cancer.
- Pregnant or lactating
- Major surgery within 4 weeks of the start of study treatment, without complete recovery
- Known hypersensitivity to any component of study treatments
- Participation in any other clinical investigation within 4 weeks of receiving the first dose of study drug
- Subjects taking metformin. Diabetics on treatment with metformin, or any other derivative thereof, must discontinue it while on study. (Other diabetic medications are allowed.)
Sites / Locations
- Scripps MD Anderson Cancer Center
- University of Florida
- University of Rochester Medical Center
- Blacktown Cancer & Haematology Centre
- John Flynn Private Hospital
- Ashford Cancer Centre
- Austin Health
Outcomes
Primary Outcome Measures
Recommended dose of SBP-101
Secondary Outcome Measures
Number of subjects with adverse events as a measure of safety and tolerability
Tumor response will be evaluated on RECIST definitions
Area under the plasma concentration versus time curve (AUC) for all three drugs
Peak plasma concentration (Cmax) for all three drugs
Full Information
NCT ID
NCT03412799
First Posted
January 19, 2018
Last Updated
May 23, 2022
Sponsor
Panbela Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03412799
Brief Title
Study of SBP-101 Combined With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
Official Title
Phase 1A/1B Dose Escalation and Expansion Study of SBP-101 in Combination With Nab-Paclitaxel and Gemcitabine in Subjects With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
June 4, 2018 (Actual)
Primary Completion Date
February 28, 2022 (Actual)
Study Completion Date
February 28, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Panbela Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label phase 1A/1B study to assess the safety, tolerability and pharmacokinetics of SBP-101 when combined with nab-paclitaxel and gemcitabine in subjects with previously untreated metastatic pancreatic ductal adenocarcinoma and to identify a recommended phase 2 dose. The study will also assess preliminary efficacy of the 3-drug treatment combination.
Detailed Description
The study will be conducted in two phases: dose escalation and expansion. Up to three dose levels of SBP-101 will be assessed in up to 18 subjects during dose escalation. The expansion phase of the study will consist of 10 additional subjects who will receive the recommended dose of SBP-101 combined with nab-paclitaxel and gemcitabine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer Metastatic, Pancreatic Cancer Stage IV, Stage IV Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
SBP-101
Other Intervention Name(s)
diethyl dihydroxyhomospermine, [(HO)2-DEHSPM]
Intervention Description
Administered as subcutaneous (SC) injection, escalating dose cohorts
Intervention Type
Drug
Intervention Name(s)
nab-paclitaxel
Other Intervention Name(s)
abraxane, protein-bound paclitaxel
Intervention Description
Administered as intravenous (IV) infusion
Intervention Type
Drug
Intervention Name(s)
Gemcitabine Injection
Other Intervention Name(s)
gemcitabine hydrochloride, Gemzar
Intervention Description
Administered as intravenous (IV) infusion
Primary Outcome Measure Information:
Title
Recommended dose of SBP-101
Time Frame
Up to 12 months following the first dose of treatment
Secondary Outcome Measure Information:
Title
Number of subjects with adverse events as a measure of safety and tolerability
Time Frame
Up to 24 months following the first dose of treatment
Title
Tumor response will be evaluated on RECIST definitions
Time Frame
Every 8 weeks during treatment assessed up to 24 months
Title
Area under the plasma concentration versus time curve (AUC) for all three drugs
Time Frame
Day 1 of Cycle 1
Title
Peak plasma concentration (Cmax) for all three drugs
Time Frame
Day 1 of Cycle 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. Patients with pancreatic acinar cell carcinoma may also be included.
Is previously untreated for metastatic pancreatic ductal adenocarcinoma, was diagnosed within the past 3 months, and is expected to receive standard treatment with gemcitabine and nab-paclitaxel.
Measurable disease on CT or MRI scan by RECIST v 1.1 criteria.
ECOG Performance Status 0 or 1.
Adult, age ≥ 18 years, male or female.
Females of child-bearing potential must have a negative serum pregnancy test within 14 days prior to start of study treatment and must use an adequate method of contraception during the study. All sexually active males must also use an adequate method of contraception during the study. Female subjects will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months of consecutive amenorrhea, without other known or suspected cause) and over 55 years old or have been sterilized surgically (i.e., bilateral tubal ligation, hysterectomy or bilateral oophorectomy, all with surgery at least one month before dosing).
Adequate bone marrow, hepatic, renal and coagulation function as defined by the following:
Absolute neutrophil count ≥1.5 x 109/L
Hemoglobin ≥9.0 g/dL (90 g/L)
Platelets ≥100 x 109/L
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) (if no hepatic metastases). If hepatic tumor involvement, AST and ALT ≤5 x ULN.
Bilirubin ≤1.5 x ULN
Prothrombin time (PT) / international normalized ratio (INR) ≤1.5 x ULN if not on anti-coagulants
Calculated creatinine clearance >50 mL/min using the Cockcroft and Gault equation
QTc interval ≤ 470 msec at Baseline.
Life expectancy ≥ 3 months.
Willing and able to provide written informed consent: voluntary agreement to participate in the study following disclosure of risks and procedures required, including possibility of onset of exocrine pancreatic insufficiency with subsequent requirement for life-long pancreatic enzyme replacement.
Exclusion Criteria:
Evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the opinion of the Investigator or Medical Monitor, makes it undesirable for the subject to participate in the study or that would jeopardize compliance with the protocol. Subjects with pre-existing well-controlled diabetes are not excluded.
Medical or psychiatric conditions that compromise the subject's ability to give informed consent or to complete the protocol or a history of non-compliance
Presence of islet-cell or pancreatic neuroendocrine tumor or mixed adenocarcinoma-neuroendocrine carcinoma
Have symptomatic central nervous system (CNS) malignancy or metastasis. Screening of asymptomatic subjects without history of CNS metastases is not required.
Serum albumin <30 g/L (3.0 g/dL)
Evidence of deep vein thrombosis or pulmonary embolism or other thromboembolic event during screening
Presence of known active bacterial, fungal, or viral infection requiring systemic therapy
Known active infection with human immunodeficiency virus (HIV), hepatitis B or C
Presence of interstitial lung disease, pulmonary fibrosis, or pulmonary hypersensitivity reaction
Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV
Maldigestion/malabsorption syndrome pre-dating the diagnosis of pancreatic cancer.
Pregnant or lactating
Major surgery within 4 weeks of the start of study treatment, without complete recovery
Known hypersensitivity to any component of study treatments
Participation in any other clinical investigation within 4 weeks of receiving the first dose of study drug
Subjects taking metformin. Diabetics on treatment with metformin, or any other derivative thereof, must discontinue it while on study. (Other diabetic medications are allowed.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suzanne Gagnon, MD
Organizational Affiliation
Panbela Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Scripps MD Anderson Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Blacktown Cancer & Haematology Centre
City
Blacktown
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Facility Name
John Flynn Private Hospital
City
Tugun
State/Province
Queensland
ZIP/Postal Code
4224
Country
Australia
Facility Name
Ashford Cancer Centre
City
Kurralta Park
State/Province
South Australia
ZIP/Postal Code
5037
Country
Australia
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
12. IPD Sharing Statement
Learn more about this trial
Study of SBP-101 Combined With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
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