First in Man Study Investigating the Biodistribution, the Safety and Optimal Recommended Dose of a New Radiolabelled Monoclonal Antibody Targeting Frizzled Homolog 10

• Status: Terminated
• Trial end date: 2015-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Advanced synovial sarcoma represents an unmet medical need. The gene encoding frizzled homologue 10 (FZD10), a 7-transmenbrane receptor, member of the Wnt signalling receptor family, is overexpressed in SS and is undetectable in normal human tissues except placenta.

OncoTherapy Science Inc. has developed a chimeric humanized monoclonal antibody (mAb) against FZD10, named OTSA101. Non-radiolabeled OTSA101 antibody has only weak antagonistic activity on SS cell growth. However, Yttrium 90-radiolabeled OTSA101 (OTSA101-DTPA-90Y) showed significant antitumor activity following a single intravenous injection in mouse xenograft model.

This first in man clinical trial (Phase I) in relapsing SS patients resistant to Doxorubicin and ifosfamide will be divided in 2 parts.

In Part 1 (imaging part using OTSA101 radiolabelled with Indium 111 [111In]), the biodistribution and tumor uptake of OTSA101-DTPA-111In will be followed using 111In as radiotracer.

In Part 2 (therapeutic part with OTSA101 radiolabelled with Yttrium 90 [90Y]), the safety and PK profiles of OTSA101-DTPA-90Y will be determined and preliminary efficacy data will be collected.

This first in Man study should allow defining the optimal recommended dose of OTSA101-DTPA-90Y.

Patients will be followed during 1 year.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Leon Berard
• Collaborator: OncoTherapy Science, Inc.
• Treatments: Antibodies; Antibodies, Monoclonal; Edetic Acid; Pentetic Acid

Criteria

Inclusion Criteria:

• Male or female patients, age ≥ 18 years.

• Histologically confirmed progressive synovial sarcoma with a minimal total tumor volume of 65mL at the time of inclusion.

• Frozen or paraffin-embedded tumor samples for immunohistochemical analysis are mandatory for registration in this study.

• Patients with doxorubicin- and ifosfamide-resistant synovial sarcoma (defined as patients with progression under doxorubicin and ifosfamide treatments or with rapid progression (i.e. within 4 months) after the last dose of doxorubicin and ifosfamide, or patients previously treated with doxorubicin and ifosfamide and with disease progression on another regimen of chemotherapy for advanced disease).

• Patients must have disease not amenable to surgery, radiation or combined modality treatment with curative intent.

• At least one measurable site of disease as defined by RECIST criteria 1.1.

• ECOG performance status of 0, 1, 2.

• Life expectancy ≥ 3 months.

• Left Ventricular Ejection Fraction (LVEF)> 50% as assessed by MUGA scan or ECHO at screening.

• Normal pulmonary function with Force Vital Capacity (FVC) of at least 60% and DLCO of at least 50%.

• Adequate bone marrow, liver and renal function including the following:

• Absolute neutrophil count ≥ 1.5 G/L, platelet count ≥ 100 G/L, and hemoglobin ≥ 10 g/dL)

• AST/ALT ≤ 3 x upper limit of normal (ULN) (or ≤ 5.0 x ULN if liver metastasis) and total bilirubin ≤ 1.5 x ULN (≤ 2.5 x ULN if liver metastases),

• Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min according to Cockroft formula.

• Adequate contraceptive methods for the whole duration of the study and for up to 12 months after the last study drug administration.

• Mandatory affiliation with a health insurance company.

• Patients must provide written informed consent before any study specific procedures or assessments, and must be willing to comply with follow up assessments and procedures.

Exclusion Criteria:

• Chemotherapy within the last 2 weeks before inclusion; radiotherapy, or any other investigational agent within 14 days or 5 half-lives, whichever is longer prior to the first dose of study drug.

• Positive human anti-mouse antibody (HAMA) or human anti-chimeric antibody (HACA) response. HAMA/HACA assays will be performed only for patients previously treated by monoclonal antibodies.

• Uncontrolled arterial hypertension: systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or both despite appropriate therapy.

• Patients with brain metastases.

• Previous history of high-dose chemotherapy with stem cell rescue.

• Chronic use of immunosuppressive drugs such as systemic corticosteroids.

• Previous therapy with monoclonal antibodies within 4 months before study entry.

• Clinically significant abnormal ECG (i.e. > grade 1) at inclusion.

• Prior history of other malignancies other than synovial sarcoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the subjects has been free of the disease for at least 3 years.

• No resolution of all specific toxicities (excluding alopecia) related to any prior anti-cancer therapy to Grade ≤ 1 according to the NCI CTCAE v4.

• Known immediate or delayed hypersensitivity reaction to 111In, 90Y, DTPA or any excipients of the investigational product.

• Psychological, familial, sociological, or geographical conditions that would limit compliance with study protocol requirements.

• Pregnant and breastfeeding women are ineligible.