Clinical trial NCT05254171: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Pancreatic Cancer Metastatic
Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer Stage IV
Keywords: SBP-101
Lead sponsor: Panbela Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-24
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization to Experimental Arm vs. Control Arm
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of first dose up to 100 weeks or until death
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From date of first dose up to 100 weeks or until death
Other outcomes:
measure: Overall Objective Response (ORR)
timeFrame: Up to 100 weeks
measure: Disease Control Rate (DCR)
timeFrame: Up to 100 weeks
measure: Duration of Response (DoR)
timeFrame: Up to 100 weeks
measure: Quality of Life (QOL) Questionnaires: EORTC QLC-C30
timeFrame: Up to 100 weeks
measure: Quality of Life (QOL) Questionnaires: QLQ-PAN26
timeFrame: Up to 100 weeks
measure: Number of Subjects with treatment-emergent adverse events as assessed by CTCAE v5.0
timeFrame: Up to 100 weeks
measure: Exploratory
timeFrame: Up to 100 weeks
Locations:
city: Hot Springs
country: United States
facility: Genesis Cancer and Blood Institute (SCRI)
state: Arkansas
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Cloud
country: United States
facility: CentraCare Health
state: Minnesota
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Columbus
country: United States
facility: Mark H Zangmeister Center - SCRI - PPDS
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology NASH - SCRI - PPDS
state: Tennessee
city: Tyler
country: United States
facility: HOPE Cancer Center of East Texas
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates - Spokane
state: Washington
city: Tacoma
country: United States
facility: MultiCare Regional Cancer Center - Tacoma
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital & the Medical College of Wisconsin
state: Wisconsin
city: Garran
country: Australia
facility: Canberra Region Cancer Centre
state: Australia Capital Territory
city: Tweed Heads
country: Australia
facility: The Tweed Hospital
state: New South Wales
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Murdoch
country: Australia
facility: St John of God Murdoch Hospital
state: Western Australia
city: Klagenfurt am Wörthersee
country: Austria
facility: Klinikum Klagenfurt Am Woerthersee
state: Kärnten
city: Sankt Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
state: Niederösterreich
city: Linz
country: Austria
facility: Ordensklinikum Linz, Krankenhaus der Barmherzigen Schwestern Linz Betriebsgesellschaft m.b.H
state: Oberösterreich
city: Steyr
country: Austria
facility: Pyhrn-Eisenwurzen Klinikum Steyr
state: Oberösterreich
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
state: Oberösterreich
city: Rankweil
country: Austria
facility: Landeskrankenhaus Feldkirch
state: Vorarlberg
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Linz
city: Salzburg
country: Austria
facility: Salzburg Cancer Research Institute
city: Wein
country: Austria
facility: A.ö. Krankenhaus der Barmherzigen Brüder
city: Wiener Neustadt
country: Austria
facility: Landesklinikum Wiener Neustadt
city: Bonheiden
country: Belgium
facility: Imelda VZW
state: Antwerpen
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
state: Belgique
city: La Louvière
country: Belgium
facility: Hôpital de Jolimont
state: Hainaut
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne
state: Luxembourg
city: Yvoir
country: Belgium
facility: CHU UCL Namur asbl - Site Godinne
state: Namur
city: Aalst
country: Belgium
facility: Onze-Lieve-Vrouwziekenhuis
state: Oost-Vlaanderen
city: Gent
country: Belgium
facility: UZ Gent
state: Oost-Vlaanderen
city: Kortrijk
country: Belgium
facility: AZ Groeninge
state: West-Vlaanderen
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi asbl
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHU de Liège
city: Marseille
country: France
facility: Hopitaux de La Timone
state: Bouches-du-Rhône
city: Caen
country: France
facility: Centre François Baclesse
state: Calvados
city: Besançon
country: France
facility: Hopital Jean Minjoz
state: Doubs
city: Toulouse
country: France
facility: Hôpital de Rangueil
state: Haute-Garonne
city: Rennes
country: France
facility: EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS
state: Ille-et-Vilaine
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden
state: Sachsen
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Tuebingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Weiden
country: Germany
facility: Klinikum Weiden
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l - PPDS
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: Azienda Unita Sanita Locale di Reggio Emilia IRCCS
state: Emilia-Romagna
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l. - PPDS
state: Lombardia
city: Milano
country: Italy
facility: Instituto Europeo Di Oncologia
state: Lombardia
city: Candiolo
country: Italy
facility: Ospedale degli Infermi
state: Piemonte
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo Della Sofferenza IRCCS
state: Puglia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Terni
country: Italy
facility: Ospedale Santa Maria Della Misericordia Di Perugia
state: Umbria
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Di Verona
state: Venito
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo di Pavia-Vialle Camillo Golgi 19
city: Seoul
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System - PPDS
state: Seoul Teugbyeolsi
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - PPDS
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Jaén
country: Spain
facility: Hospital Universitario de Jaen
state: Jaen
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro - CIOCC
state: Madrid, Communidad Delaware
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de La Arrixaca
state: Murcia
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra
state: Navarra
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
state: Vizcaya
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruña
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Girona
country: Spain
facility: Institut Catala d'Oncologia Girona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid - España
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Hospital General
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - PPDS
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary - PPDS
state: Aberdeen City
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: City Of London
city: Plympton
country: United Kingdom
facility: Derriford Hospital
state: Devon
Study officials:
affiliation: Panbela Therapeutics, Inc.
name: Michael J Walker, MD
role: STUDY_DIRECTOR
References: