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

• ClinicalTrials.gov Identifier: NCT02528526
• Recruitment Status: Unknown
• First Posted: August 19, 2015
• Last Update Posted: August 19, 2015
• Sponsor: University of Zurich
• Information provided by (Responsible Party): University of Zurich

Tracking Information

• First Submitted Date: November 11, 2014
• First Posted Date: August 19, 2015
• Last Update Posted Date: August 19, 2015
• Study Start Date: February 2014
• Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 18, 2015)

Safety and tolerability as measured by collection of adverse effects information [ Time Frame: 10 weeks ]

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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 18, 2015)

• Efficacy as measured by FDG-PET scan [ Time Frame: 5 months ]
  Assessment of tumor response with 18F-FDG PET in FDG-avid tumors using EORTC criteria
• Efficacy as measured by MRI [ Time Frame: 5 months ]
  Assessment of tumor response with MRI in non-FDG-avid tumors using RECIST criteria

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effects of OXY111A in Primary and Secondary Hepato-Pancreato-Biliary Neoplasm
• Official Title: A Phase IB/IIA, Single-centered Study of the Effects of OXY111A in Primary and Secondary Hepato-Pancreato-Biliary Neoplasia
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Pancreatic Neoplasms
• Hepatocellular Cancer
• Cholangiocarcinoma
• Colorectal Neoplasms

Intervention

Drug: OXY111A

OXY111A intravenous infusion

Other Name: Myo-inositol trispyrophosphate

Study Arms

Experimental: Treatment

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

Intervention: Drug: OXY111A

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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 18, 2015): 69
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2016
• Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT02528526
• Other Study ID Numbers: OXY1A_2014-0374
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Zurich
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Zurich
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Pierre Alain, Clavien; University Hospital Zurich, Visceral Surgery

• PRS Account: University of Zurich
• Verification Date: August 2015