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Effects of OXY111A in Primary and Secondary Hepato-Pancreato-Biliary Neoplasm (OXY1A)

Primary Purpose

Pancreatic Neoplasms, Hepatocellular Cancer, Cholangiocarcinoma

Status

Unknown status

Phase

Phase 1

Locations

Switzerland

Study Type

Interventional

Intervention

OXY111A

About this trial

This is an interventional treatment trial for Pancreatic Neoplasms focused on measuring Hypoxia, Pancreatic Neoplasms, Hepatocellular Cancer, Cholangiocarcinoma, Colorectal Neoplasms, Treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

University Hospital Zurich, Visceral SurgeryRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Efficacy as measured by FDG-PET scan

Assessment of tumor response with 18F-FDG PET in FDG-avid tumors using EORTC criteria

Efficacy as measured by MRI

Assessment of tumor response with MRI in non-FDG-avid tumors using RECIST criteria

Full Information

NCT ID

NCT02528526

First Posted

November 11, 2014

Last Updated

August 18, 2015

Sponsor

University of Zurich

1. Study Identification

Unique Protocol Identification Number

NCT02528526

Brief Title

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

Acronym

OXY1A

Official Title

A Phase IB/IIA, Single-centered Study of the Effects of OXY111A in Primary and Secondary Hepato-Pancreato-Biliary Neoplasia

Study Type

Interventional

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Unknown status

Study Start Date

February 2014 (undefined)

Primary Completion Date

December 2016 (Anticipated)

Study Completion Date

December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Zurich

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Neoplasms, Hepatocellular Cancer, Cholangiocarcinoma, Colorectal Neoplasms

Keywords

Hypoxia, Pancreatic Neoplasms, Hepatocellular Cancer, Cholangiocarcinoma, Colorectal Neoplasms, Treatment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

69 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

OXY111A

Other Intervention Name(s)

Myo-inositol trispyrophosphate

Intervention Description

OXY111A intravenous infusion

Primary Outcome Measure Information:

Title

Safety and tolerability as measured by collection of adverse effects information

Description

Safety variables and patient tolerance as measured by collection of adverse effects information according to Common Terminology Criteria for Adverse Events (CTCAE)

Time Frame

10 weeks

Secondary Outcome Measure Information:

Title

Efficacy as measured by FDG-PET scan

Description

Assessment of tumor response with 18F-FDG PET in FDG-avid tumors using EORTC criteria

Time Frame

5 months

Title

Efficacy as measured by MRI

Description

Assessment of tumor response with MRI in non-FDG-avid tumors using RECIST criteria

Time Frame

5 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Pierre-Alain Clavien, MD, PhD

Phone

+41 (0)44 255 33 00

clavien@access.uzh.ch

First Name & Middle Initial & Last Name or Official Title & Degree

Perparim Limani, MD

Phone

+41 (0)44 255 33 00

perparim.limani@usz.ch

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pierre Alain, Clavien

Organizational Affiliation

University Hospital Zurich, Visceral Surgery

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Zurich, Visceral Surgery

City

Zurich

State/Province

ZIP/Postal Code

8091

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pierre-Alain Clavien, MD, PhD

Phone

+41 (0)44 255 33 00

clavien@access.uzh.ch

First Name & Middle Initial & Last Name & Degree

Perparim Limani, MD

Phone

+41 (0)44 255 33 00

perparim.limani@usz.ch

First Name & Middle Initial & Last Name & Degree

Panagiotis Samaras, MD

First Name & Middle Initial & Last Name & Degree

Bernhard Pestalozzi, MD

First Name & Middle Initial & Last Name & Degree

Alexander Jetter, MD

First Name & Middle Initial & Last Name & Degree

Michael Linecker, MD

First Name & Middle Initial & Last Name & Degree

Rolf Graf, PhD

First Name & Middle Initial & Last Name & Degree

Bostjan Humar, PhD

First Name & Middle Initial & Last Name & Degree

Henrik Petrowsky, MD

First Name & Middle Initial & Last Name & Degree

Philipp Kron, MD

First Name & Middle Initial & Last Name & Degree

Roger Stupp, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

21370375

Citation

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.

Results Reference

background

PubMed Identifier

23045284

Citation

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.

Results Reference

background

PubMed Identifier

23471434

Citation

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.

Results Reference

background

PubMed Identifier

24214898

Citation

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.

Results Reference

background

PubMed Identifier

15745806

Citation

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.

Results Reference

background

PubMed Identifier

34155211

Citation

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.

Results Reference

derived

PubMed Identifier

27756258

Citation

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.

Results Reference

derived

Links:

URL

http://www.vis.usz.ch

Description

Department of Surgery, University Hospital Zurich, Switzerland

URL

http://www.hpb-center.ch

Description

Swiss Hepato-Pancreato-Biliary (HPB) Center, University Hospital Zurich, Switzerland

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

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