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

Colorectal Neoplasms Clinical Trial

— OXY1A  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02528526
• Other study ID #: OXY1A_2014-0374
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: November 11, 2014
• Last updated: August 18, 2015
• Start date: February 2014
• Est. completion date: December 2016

Study information

• Verified date: August 2015
• Source: University of Zurich
• Contact: Pierre-Alain Clavien, MD, PhD
• Phone: +41 (0)44 255 33 00
• Email: clavien[@]access.uzh.ch
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 69
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Colorectal Neoplasms
• Hepatocellular Cancer
• Liver Neoplasms
• Neoplasms
• Pancreatic Neoplasms

Intervention

Drug:
• OXY111A
OXY111A intravenous infusion

Locations

Country	Name	City	State
Switzerland	University Hospital Zurich, Visceral Surgery	Zurich	ZH

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

References & Publications (5)

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-1a 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. — View 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. — View 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. — View 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 pO2 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Efficacy as measured by FDG-PET scan	Assessment of tumor response with 18F-FDG PET in FDG-avid tumors using EORTC criteria	5 months	Yes
Secondary	Efficacy as measured by MRI	Assessment of tumor response with MRI in non-FDG-avid tumors using RECIST criteria	5 months	Yes

External Links

•   Department of Surgery, University Hospital Zurich, Switzerland
•   Swiss Hepato-Pancreato-Biliary (HPB) Center, University Hospital Zurich, Switzerland