Effects Of OXY111A In Primary And Secondary Hepato-Pancreato-Biliary Neoplasm

Study Overview

Effects of OXY111A in Primary and Secondary Hepato-Pancreato-Biliary Neoplasm

The purpose of the study is to evaluate whether the novel anti-cancer drug OXY111A is safe and tolerated in patients with primary and secondary hepato-pancreato-biliary and gastrointestinal neoplasia as measured by exploring the maximum tolerated dose (MTD). At level of MTD, additional patients will be included aimed for assessing the efficacy profile in these neoplasia entities.

The IMP OXY111A counteracts hypoxia-induced tumor aggressiveness showing decreased tumor burden and increased survival in five different animal solid tumor models both applied as monotherapy and increased beneficial effects when followed by standard chemotherapy. The unique ability of the IMP counteract hypoxic tumor behaviour along with its non-toxic side effects tested both in animals and healthy volunteers is of outmost interest to explore in patients with solid tumors. The study seeks primarily to determine the safety and tolerability of OXY111A in patients with primary and secondary hepato-pancreato-biliary and gastrointestinal neoplasia as measured by exploring the MTD in a conservative 3+3 dose escalation schedule. The window for DLT assessment is from first dose of study drug until first dose of standard of care chemotherapy or 10 days following completion of last dose of study drug (whichever is shorter in duration). Additionally, we will assess efficacy of OXY111A on decreasing tumor volume, metabolic activity, as well as circulatory tumor and angiogenic markers.

Pancreatic Neoplasms
Hepatocellular Cancer
Cholangiocarcinoma
Colorectal Neoplasms

DRUG: OXY111A

OXY1A_2014-0374

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-11-11	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2015-08-18
First Submitted that Met QC Criteria 2015-08-18	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2015-08-19
First Posted (ESTIMATED) 2015-08-19	Results First Posted N/A	Last Verified 2015-08

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment Add-on application of Myo-inositol trispyrophosphate, total of 9 times, 3 applications per week, over 3 weeks.	DRUG: OXY111A OXY111A intravenous infusion

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment

Add-on application of Myo-inositol trispyrophosphate, total of 9 times, 3 applications per week, over 3 weeks.

DRUG: OXY111A

OXY111A intravenous infusion

Primary Outcome Measures	Measure Description	Time Frame
Safety and tolerability as measured by collection of adverse effects information	Safety variables and patient tolerance as measured by collection of adverse effects information according to Common Terminology Criteria for Adverse Events (CTCAE)	10 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Efficacy as measured by FDG-PET scan	Assessment of tumor response with 18F-FDG PET in FDG-avid tumors using EORTC criteria	5 months
Efficacy as measured by MRI	Assessment of tumor response with MRI in non-FDG-avid tumors using RECIST criteria	5 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Pierre-Alain Clavien, MD, PhD

Phone Number: +41 (0)44 255 33 00

Email: clavien@access.uzh.ch

Study Contact Backup

Name: Perparim Limani, MD

Phone Number: +41 (0)44 255 33 00

Email: perparim.limani@usz.ch

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Study Indication: patients diagnosed for non-resectable hepato-pancreato-biliary or gastrointestinal neoplasm
Male and Female patients ≥ 18 years of age
Signed Informed Consent after being informed
Eastern Cooperative Oncology Group (ECOG) performance status score of ≥ 2 at study entry.
A life-expectancy of >3 months
Adequate hematologic and renal function
Use of effective contraception (per the institutional standard), if procreative potential exists
Adequate recovery from recent surgery, chemotherapy, and radiation therapy. At least 28 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy (palliative radiation therapy is allowed)
Accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center

Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product
Women who are pregnant or breast feeding

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Pierre Alain, Clavien, University Hospital Zurich, Visceral Surgery

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Aprahamian M, Bour G, Akladios CY, Fylaktakidou K, Greferath R, Soler L, Marescaux J, Egly JM, Lehn JM, Nicolau C. Myo-InositolTrisPyroPhosphate treatment leads to HIF-1alpha suppression and eradication of early hepatoma tumors in rats. Chembiochem. 2011 Mar 21;12(5):777-83. doi: 10.1002/cbic.201000619. Epub 2011 Mar 2.
Derbal-Wolfrom L, Pencreach E, Saandi T, Aprahamian M, Martin E, Greferath R, Tufa E, Choquet P, Lehn JM, Nicolau C, Duluc I, Freund JN. Increasing the oxygen load by treatment with myo-inositol trispyrophosphate reduces growth of colon cancer and modulates the intestine homeobox gene Cdx2. Oncogene. 2013 Sep 5;32(36):4313-8. doi: 10.1038/onc.2012.445. Epub 2012 Oct 8.
Kieda C, El Hafny-Rahbi B, Collet G, Lamerant-Fayel N, Grillon C, Guichard A, Dulak J, Jozkowicz A, Kotlinowski J, Fylaktakidou KC, Vidal A, Auzeloux P, Miot-Noirault E, Beloeil JC, Lehn JM, Nicolau C. Stable tumor vessel normalization with pO(2) increase and endothelial PTEN activation by inositol trispyrophosphate brings novel tumor treatment. J Mol Med (Berl). 2013 Jul;91(7):883-99. doi: 10.1007/s00109-013-0992-6. Epub 2013 Mar 9.
Raykov Z, Grekova SP, Bour G, Lehn JM, Giese NA, Nicolau C, Aprahamian M. Myo-inositol trispyrophosphate-mediated hypoxia reversion controls pancreatic cancer in rodents and enhances gemcitabine efficacy. Int J Cancer. 2014 Jun 1;134(11):2572-82. doi: 10.1002/ijc.28597. Epub 2013 Nov 25.
Fylaktakidou KC, Lehn JM, Greferath R, Nicolau C. Inositol tripyrophosphate: a new membrane permeant allosteric effector of haemoglobin. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1605-8. doi: 10.1016/j.bmcl.2005.01.064.
Schneider MA, Linecker M, Fritsch R, Muehlematter UJ, Stocker D, Pestalozzi B, Samaras P, Jetter A, Kron P, Petrowsky H, Nicolau C, Lehn JM, Humar B, Graf R, Clavien PA, Limani P. Phase Ib dose-escalation study of the hypoxia-modifier Myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors. Nat Commun. 2021 Jun 21;12(1):3807. doi: 10.1038/s41467-021-24069-w.
Limani P, Linecker M, Kron P, Samaras P, Pestalozzi B, Stupp R, Jetter A, Dutkowski P, Mullhaupt B, Schlegel A, Nicolau C, Lehn JM, Petrowsky H, Humar B, Graf R, Clavien PA. Development of OXY111A, a novel hypoxia-modifier as a potential antitumor agent in patients with hepato-pancreato-biliary neoplasms - Protocol of a first Ib/IIa clinical trial. BMC Cancer. 2016 Oct 19;16(1):812. doi: 10.1186/s12885-016-2855-3.

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