Study of SBP-101 Combined With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer

Stage IV Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03412799
• Other study ID #: CL-SBP-101-03
• Status: Completed
• Phase: Phase 1
• Start date: June 4, 2018
• Est. completion date: February 28, 2022

Study information

• Verified date: May 2022
• Source: Panbela Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: February 28, 2022
• Est. primary completion date: February 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. Absolute neutrophil count =1.5 x 109/L

2. Hemoglobin =9.0 g/dL (90 g/L)

3. Platelets =100 x 109/L

4. 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.

5. Bilirubin =1.5 x ULN

6. Prothrombin time (PT) / international normalized ratio (INR) =1.5 x ULN if not on anti-coagulants

7. 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.)

Related Conditions & MeSH terms

• Pancreatic Cancer Metastatic
• Pancreatic Cancer Stage IV
• Pancreatic Neoplasms
• Stage IV Pancreatic Cancer

Intervention

Drug:
• SBP-101
Administered as subcutaneous (SC) injection, escalating dose cohorts
• nab-paclitaxel
Administered as intravenous (IV) infusion
• Gemcitabine Injection
Administered as intravenous (IV) infusion

Locations

Country	Name	City	State
Australia	Blacktown Cancer & Haematology Centre	Blacktown	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	Ashford Cancer Centre	Kurralta Park	South Australia
Australia	John Flynn Private Hospital	Tugun	Queensland
United States	University of Florida	Gainesville	Florida
United States	Scripps MD Anderson Cancer Center	La Jolla	California
United States	University of Rochester Medical Center	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Panbela Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended dose of SBP-101		Up to 12 months following the first dose of treatment
Secondary	Number of subjects with adverse events as a measure of safety and tolerability		Up to 24 months following the first dose of treatment
Secondary	Tumor response will be evaluated on RECIST definitions		Every 8 weeks during treatment assessed up to 24 months
Secondary	Area under the plasma concentration versus time curve (AUC) for all three drugs		Day 1 of Cycle 1
Secondary	Peak plasma concentration (Cmax) for all three drugs		Day 1 of Cycle 1