Study of Nab-Paclitaxel and Gemcitabine With or Without SBP-101 in Pancreatic Cancer (ASPIRE)

• ClinicalTrials.gov Identifier: NCT05254171
• Recruitment Status: Recruiting
• First Posted: February 24, 2022
• Last Update Posted: April 16, 2024
• Sponsor: Panbela Therapeutics, Inc.
• Information provided by (Responsible Party): Panbela Therapeutics, Inc.

Tracking Information

• First Submitted Date: January 13, 2022
• First Posted Date: February 24, 2022
• Last Update Posted Date: April 16, 2024
• Actual Study Start Date: August 8, 2022
• Estimated Primary Completion Date: August 29, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2024)

Overall Survival (OS) [ Time Frame: From date of first dose up to 100 weeks or until death ]

Compare OS between subjects who receive SBP-101 and those who do not receive SBP-101 (i.e., placebo) in combination with nab-paclitaxel and gemcitabine

Original Primary Outcome Measures (submitted: February 21, 2022)

Overall Survival (OS) [ Time Frame: Randomization (Day 1) until death from any cause assessed up to 36 months ]

Compare OS between subjects who receive SBP-101 and those who do not receive SBP-101 (i.e., placebo) in combination with nab-paclitaxel and gemcitabine

Current Secondary Outcome Measures (submitted: March 12, 2024)

Progression Free Survival (PFS) [ Time Frame: From date of first dose up to 100 weeks or until death ]

Compare PFS between SBP-101 and placebo

Original Secondary Outcome Measures (submitted: February 21, 2022)

Progression Free Survival (PFS) [ Time Frame: Randomization (Day 1) until disease progression or death from any cause, whichever occurs first, assessed up to 36 months ]

Compare PFS between SBP-101 and placebo

Current Other Pre-specified Outcome Measures (submitted: March 12, 2024)

• Overall Objective Response (ORR) [ Time Frame: Up to 100 weeks ]
  Compare ORR between SBP-101 and placebo
• Disease Control Rate (DCR) [ Time Frame: Up to 100 weeks ]
  Compare DCR between SBP-101 and placebo
• Duration of Response (DoR) [ Time Frame: Up to 100 weeks ]
  Compare DoR between SBP-101 and placebo
• Quality of Life (QOL) Questionnaires: EORTC QLC-C30 [ Time Frame: Up to 100 weeks ]
  Compare QOL changes in scores between SBP-101 and placebo
• Quality of Life (QOL) Questionnaires: QLQ-PAN26 [ Time Frame: Up to 100 weeks ]
  Compare QOL changes in scores between SBP-101 and placebo
• Number of Subjects with treatment-emergent adverse events as assessed by CTCAE v5.0 [ Time Frame: Up to 100 weeks ]
  Compare Safety and Tolerability of SBP-101 to placebo when administered in combination with nab-paclitaxel and gemcitabine
• Exploratory [ Time Frame: Up to 100 weeks ]
  Compare effects of SBP-101 and placebo on blood levels of carbohydrate antigen (CA) CA 19-9 and circulating tumor DNA (cT DNA). ctDNA analysis will be done only on subjects enrolled prior to Interim Analysis.

Original Other Pre-specified Outcome Measures (submitted: February 21, 2022)

• Overall Objective Response (ORR) [ Time Frame: Every 8 weeks during treatment for up to 36 months ]
  Compare ORR between SBP-101 and placebo
• Disease Control Rate (DCR) [ Time Frame: At least 16 weeks ]
  Compare DCR between SBP-101 and placebo
• Duration of Response (DoR) [ Time Frame: Onset of CR or PR until disease progression assessed up to 36 months ]
  Compare DoR between SBP-101 and placebo
• Quality of Life (QOL) Questionnaires: EORTC QLC-C30 [ Time Frame: Every 4 weeks during treatment for up to 36 months ]
  Compare QOL changes in scores between SBP-101 and placebo
• Quality of Life (QOL) Questionnaires: QLQ-PAN26 [ Time Frame: Every 4 weeks during treatment for up to 36 months ]
  Compare QOL changes in scores between SBP-101 and placebo
• Number of Subjects with treatment-emergent adverse events as assessed by CTCAE v5.0 [ Time Frame: Up to 36 months ]
  Compare Safety and Tolerability of SBP-101 to placebo when administered in combination with nab-paclitaxel and gemcitabine
• Exploratory [ Time Frame: Baseline to week 8 and maximum decrease overall assessed for up to 36 months ]
  Compare effects of SBP-101 and placebo on blood levels of CA 19-9 and circulating tumor DNA (cT DNA)

Descriptive Information

• Brief Title: Study of Nab-Paclitaxel and Gemcitabine With or Without SBP-101 in Pancreatic Cancer
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of Nab-Paclitaxel and Gemcitabine With or Without SBP-101 in Subjects Previously Untreated for Metastatic Pancreatic Ductal Adenocarcinoma
• Brief Summary: The study is a randomized, double-blind, placebo-controlled, multicenter study of standard treatment with nab-paclitaxel and gemcitabine with or without SBP-101 in subjects previously untreated for metastatic pancreatic ductal adenocarcinoma (PDA), including subjects who have received prior neoadjuvant or adjuvant treatment.
• Detailed Description: This trial will enroll approximately 600 patients to evaluate the effect of SBP-101 on Overall Survival when administered with gemcitabine and nab-paclitaxel compared to gemcitabine and nab-paclitaxel and a placebo. Secondary endpoints include Progression-free survival, radiologic responses to treatment, and Quality of Life measures. An independent, external Data Safety Monitoring Board (DSMB) will monitor safety and efficacy and a planned futility analysis.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

1:1 randomization to Experimental Arm vs. Control Arm

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Pancreatic Cancer Metastatic
• Pancreatic Ductal Adenocarcinoma
• Pancreatic Cancer Stage IV

Intervention

• Drug: SBP-101
  small molecule polyamine metabolic inhibitor for subcutaneous injection
  Other Name: ivospemin
• Drug: Nab-paclitaxel
  paclitaxel protein-bound particles for injectable suspension
  Other Name: Abraxane
• Drug: Gemcitabine
  gemcitabine for injection
  Other Name: Gemzar
• Other: Placebo
  Normal Saline

Study Arms

• Experimental: Experimental Arm
  SBP-101 + Nab-paclitaxel and Gemcitabine
  Interventions:

  • Drug: SBP-101
  • Drug: Nab-paclitaxel
  • Drug: Gemcitabine
• Placebo Comparator: Control Arm
  Placebo + Nab-Paclitaxel and Gemcitabine
  Interventions:

  • Drug: Nab-paclitaxel
  • Drug: Gemcitabine
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 12, 2024): 600
• Original Estimated Enrollment (submitted: February 21, 2022): 150
• Estimated Study Completion Date: January 1, 2027
• Estimated Primary Completion Date: August 29, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma.
• Is previously untreated for metastatic pancreatic ductal adenocarcinoma; metastatic disease must have been diagnosed within the past 3 months; and subject is expected to receive standard treatment with gemcitabine and nab-paclitaxel. Subjects who have had planned or prior surgery, such as a Whipple procedure, with or without neo-adjuvant/or adjuvant chemotherapy may be included.
• Life expectancy ≥ 3 months.
• Measurable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan by RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• 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 from 2 weeks before the first administration of SBP-101 until 6 months after the last administration of study drug (i.e., last dose of any of the three drugs in the regimen). Female subjects are 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 and renal function as outlined in protocol.
• QTc interval ≤ 470 ms (for women) and ≤ 450 ms (for men) on the ECG at baseline calculated by either the Fridericia or Framingham formula.
• Willing and able to provide written informed consent: voluntary agreement to participate in the study following disclosure of risks and procedures required.

Exclusion Criteria:

• When results of germline or somatic testing done prior to screening are known, subjects known to have mutations of the BRCA 1/2 (Breast Cancer gene) are excluded.
• Concomitant metformin administration. Diabetic subjects on treatment with metformin, or any other derivative thereof, must discontinue it at least 5 days prior to C1D1 and not take metformin while on study (other diabetic medications are allowed).
• Any history of retinopathy or at risk for retinal detachment (personal or family history of retinal detachment, extreme myopia [-6.0 diopters or approximately 20/500], eye surgery <6 months prior to C1D1, or history of a severe eye injury. Subjects with findings of retinopathy on baseline ophthalmology exams will be excluded.
• 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.
• 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).
• Deep vein thrombosis (DVT) or portal vein occlusion, pulmonary embolism (PE), or other thromboembolic event that occurs 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.
• Pregnant or lactating.
• Major surgery within 4 weeks prior to the start of study drug 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.
• Any history of hydroxychloroquine use (Plaquenil® and other brand names).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Rachel Bragg, MPH; 952-479-1196; rbragg@panbela.com

Contact: Tammy Groene; 952-479-1196; tgroene@panbela.com

• Listed Location Countries: Australia, Austria, Belgium, France, Germany, Italy, Korea, Republic of, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05254171
• Other Study ID Numbers: CL-SBP-101-04
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Panbela Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Panbela Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Michael J Walker, MD; Panbela Therapeutics, Inc.

• PRS Account: Panbela Therapeutics, Inc.
• Verification Date: April 2024