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

Pancreatic Ductal Adenocarcinoma Clinical Trial

— ASPIRE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05254171
• Other study ID #: CL-SBP-101-04
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 8, 2022
• Est. completion date: January 1, 2027

Study information

• Verified date: April 2024
• Source: Panbela Therapeutics, Inc.
• Contact: Rachel Bragg, MPH
• Phone: 952-479-1196
• Email: rbragg[@]panbela.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: January 1, 2027
• Est. primary completion date: August 29, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

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

Intervention

Drug:
• SBP-101
small molecule polyamine metabolic inhibitor for subcutaneous injection
• Nab-paclitaxel
paclitaxel protein-bound particles for injectable suspension
• Gemcitabine
gemcitabine for injection

Other:
• Placebo
Normal Saline

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Panbela Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  France,  Germany,  Italy,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Objective Response (ORR)	Compare ORR between SBP-101 and placebo	Up to 100 weeks
Other	Disease Control Rate (DCR)	Compare DCR between SBP-101 and placebo	Up to 100 weeks
Other	Duration of Response (DoR)	Compare DoR between SBP-101 and placebo	Up to 100 weeks
Other	Quality of Life (QOL) Questionnaires: EORTC QLC-C30	Compare QOL changes in scores between SBP-101 and placebo	Up to 100 weeks
Other	Quality of Life (QOL) Questionnaires: QLQ-PAN26	Compare QOL changes in scores between SBP-101 and placebo	Up to 100 weeks
Other	Number of Subjects with treatment-emergent adverse events as assessed by CTCAE v5.0	Compare Safety and Tolerability of SBP-101 to placebo when administered in combination with nab-paclitaxel and gemcitabine	Up to 100 weeks
Other	Exploratory	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.	Up to 100 weeks
Primary	Overall Survival (OS)	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	From date of first dose up to 100 weeks or until death
Secondary	Progression Free Survival (PFS)	Compare PFS between SBP-101 and placebo	From date of first dose up to 100 weeks or until death