A Phase I, First-in-man Study of OTX008 Given Subcutaneously as a Single Agent to Patients With Advanced Solid Tumors

The purpose of this study is to determine the recommended dose (RD) for further phase II studies, of the Galectin-1 inhibitor OTX008 given subcutaneously in patients with advanced solid tumors

Study Overview

• Status: Unknown
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: OTX008

Detailed Description

Overexpression of galectin-1 protein is well documented in different types of cancers, with associated bad prognostic and enhanced metastases spreading.

In-vitro/in-vivo preclinical studies showed that OTX008 inhibits galectin-1 expression. In different cancer models in animals, OTX008 reduced tumor growing and metastases spreading and it was observed a blood vessels architecture normalization.

Thus, OTX008 appears to be an innovating approach to treat cancers and this clinical phase I study aims to evaluate OTX008 therapy in patients with advanced solid tumors.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Patrice HERAIT, MD; Phone Number: 00 18 +33 6 85 12; Email: pherait@phconsult-onco.com

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Recruiting
    • Institut Jules Bordet
    • Contact: Ahmad AWADA, MD; Phone Number: 31 89 +32 2 541; Email: ahmad.awada@bordet.be
    • Principal Investigator: Ahmad AWADA, MD
• France
  • Clichy, France, 92110
    • Recruiting
    • Hopital Beaujon - AP-HP
    • Contact: Eric RAYMOND, MD; Phone Number: 56 17 +33 1 40 87; Email: eric.raymond@bjn.aphp.fr
    • Principal Investigator: Eric Raymond, MD
  • Toulouse, France, 31052
    • Recruiting
    • Institut Claudius Regaud
    • Contact: Jean-Pierre DELORD, MD; Phone Number: 25 67 +33 5 67 22; Email: delord.jean-pierre@claudiusregaud.fr
    • Principal Investigator: Jean-Pierre DELORD, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent prior to beginning protocol specific screening procedures. Patients registered in this trial must be treated and followed at the participating centers. Patients should receive the study treatment within 7 days after registration
• Histologically proven malignant solid tumor
• Patients having failed all standard therapies, or for whom standard therapies are deemed ineffective or contra-indicated.
• Patients aged > 18 years.
• ECOG performance status (PS) of 0 to 1
• Off previous systemic therapy (except LH-RH agonist therapy started > 2 months prior to study entry that could be continued) , radiation therapy, or surgery for at least 30 days prior to first study treatment administration (45 days for bicalutamide).
• Recovery from the toxic effects of prior treatment to NCIC-CTC grade < 1, except alopecia
• Adequate bone marrow function including: Neutrophils >= 1.5 x 10E9 /L; platelets >= 100 x 10E9 /L, Hb > 8g/dL without transfusion.
• Creatinine clearance >= 60 mL/min (Cockroft & Gault formula, or MDRD formula for patients aged > 65 years).
• Adequate LFTs: Total bilirubin < 1 x the institutional upper normal limits (UNL); ALAT/ASAT >= 3 x UNL (or >= 5 x UNL in case of liver metastases).
• Serum albumin > 28g/L.
• Availability of the last tumor imaging within 6 months prior to baseline tumor imaging
• Availability of archived pathology specimen (paraffin-embedded block) from the tumor

Exclusion Criteria:

• History of prior malignancy other than those previously treated with a curative intent more than 5 years ago and without relapse (any tumor) or basal cell skin cancer, in situ cervical cancer, superficial bladder cancer, or high grade intestinal polyps treated adequately, regardless of the disease-free interval.
• Pregnant or lactating women or women of childbearing potential not using adequate contraception. Male patients not using adequate contraception.
• Tumor sites that necessitate immediate intervention (supportive care, surgery or radiation therapy) such as symptomatic brain or leptomeningeal tumor, spinal cord compression, other compressive tumor masses, painful bone metastasis, bone fracture, etc…

• Other serious illness or medical conditions, which, in the investigator's opinion could jeopardize patient's safety or hamper understanding of the study by the patient, patient's compliance to study treatment, or interpretation of study results. These conditions include (but are not restricted to):

  1. Congestive heart failure or angina pectoris not medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or arrhythmias.
  2. Existence of significant neurologic or psychiatric disorders impairing the ability to obtain consent.
  3. Active infection.
• Concurrent treatment with other experimental therapies or participation in another clinical trial within 30 days prior to first study treatment administration.
• Concurrent treatment with any other anticancer therapy (except LH-RH agonist therapy initiated > 2 months prior to study entry).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OTX008; Single-arm study of OTX008 given subcutaneously, daily without interruption to patients with advanced solid tumors. Starting dose: 65 mg/day.	Drug: OTX008; OTX008 given daily without interruption, subcutaneously. Starting dose: 65 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity	Dose Limiting Toxicity (DLT) will be assessed during the first 21 days (3 weeks)of OTX008 treatment in each patient to determine Recommended Dose (RD)	up to 3 weeks of OTX008 treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK)	OTX008 plasma concentration will be assessed at days 1, 2 and 22 of OTX008 treatment to determine PK profile of OTX008. Following parameters will be used: Trough (Cmin) and peak (Cmax) of OTX008 concentrations, Tmax, t1/2, steady state, total clearance, AUC (Area Under Curve)	Days 1, 2 and 22 of OTX008 treatment
Pharmacodynamics (PD)	Following parameter will be measured: plasma levels of galectin-1	Days 1 and 22 of OTX008 treatment

Collaborators and Investigators

• Sponsor: Oncoethix GmbH

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Anticipated): May 1, 2013
• Study Completion (Anticipated): May 1, 2013

Study Registration Dates

• First Submitted: November 2, 2012
• First Submitted That Met QC Criteria: November 6, 2012
• First Posted (Estimate): November 9, 2012

Study Record Updates

• Last Update Posted (Estimate): November 9, 2012
• Last Update Submitted That Met QC Criteria: November 6, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: cancer; solid tumors; phase I; first-in-man; galectin
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: OTX008_101