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

• ClinicalTrials.gov Identifier: NCT03412799
• Recruitment Status: Active, not recruiting
• First Posted: January 26, 2018
• Last Update Posted: January 12, 2022
• Sponsor: Panbela Therapeutics, Inc.
• Information provided by (Responsible Party): Panbela Therapeutics, Inc.

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.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer Metastatic; Pancreatic Cancer Stage IV; Stage IV Pancreatic Cancer	Drug: SBP-101; Drug: nab-paclitaxel; Drug: Gemcitabine Injection	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 4, 2018
• Estimated Primary Completion Date: February 28, 2022
• Estimated Study Completion Date: February 28, 2022

Arms and Interventions

Intervention Details:

• Drug: SBP-101
  Administered as subcutaneous (SC) injection, escalating dose cohorts
  Other Names:

  • diethyl dihydroxyhomospermine
  • [(HO)2-DEHSPM]
• Drug: nab-paclitaxel
  Administered as intravenous (IV) infusion
  Other Names:

  • abraxane
  • protein-bound paclitaxel
• Drug: Gemcitabine Injection
  Administered as intravenous (IV) infusion
  Other Names:

  • gemcitabine hydrochloride
  • Gemzar

Outcome Measures

Primary Outcome Measures :

1. Recommended dose of SBP-101 [ Time Frame: Up to 12 months following the first dose of treatment ]

Secondary Outcome Measures :

1. 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 ]
2. Tumor response will be evaluated on RECIST definitions [ Time Frame: Every 8 weeks during treatment assessed up to 24 months ]
3. Area under the plasma concentration versus time curve (AUC) for all three drugs [ Time Frame: Day 1 of Cycle 1 ]
4. Peak plasma concentration (Cmax) for all three drugs [ Time Frame: Day 1 of Cycle 1 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

  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.)

Contacts and Locations

Locations

United States, California

Scripps MD Anderson Cancer Center

La Jolla, California, United States, 92037

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

United States, New York

University of Rochester Medical Center

Rochester, New York, United States, 14642

Australia, New South Wales

Blacktown Cancer & Haematology Centre

Blacktown, New South Wales, Australia, 2148

Australia, Queensland

John Flynn Private Hospital

Tugun, Queensland, Australia, 4224

Australia, South Australia

Ashford Cancer Centre

Kurralta Park, South Australia, Australia, 5037

Australia, Victoria

Austin Health

Heidelberg, Victoria, Australia, 3084

Sponsors and Collaborators

Panbela Therapeutics, Inc.

Investigators

• Study Director: Suzanne Gagnon, MD; Panbela Therapeutics, Inc.

More Information

• Responsible Party: Panbela Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03412799
• Other Study ID Numbers: CL-SBP-101-03
• First Posted: January 26, 2018
• Last Update Posted: January 12, 2022
• Last Verified: January 2022

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

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs