A Trial of ASP7487 (OSI-906) in Combination With Bortezomib for the Treatment of Relapsed Multiple Myeloma

Stopped early · Phase 1/Phase 2

Conditions studied: Multiple Myeloma

In brief

This is a multi-center, open-label, non-randomized study. Patients will receive ASP7487 (OSI-906) in combination with bortezomib and dexamethasone. Phase 1 involves dose escalation of the combination, whereas Phase 2 involves the expansion of ASP7487 (OSI-906) combined with bortezomib and dexamethasone at the MTD to establish the ORR. This trial will accrue patients with relapsed or relapsed/refractory MM - a disease state for which bortezomib is approved to treat by the FDA and Health Canada. The combination of ASP7487 (OSI-906) with bortezomib is supported by pre-clinical work in MM in which the combination with an IGF1-R inhibitor enhances anti-tumor activity of bortezomib.

Key facts

Study ID

NCT01672736

Run by

University Health Network, Toronto

People needed

19

Starts

2012-09-01

Expected to finish

2017-12-27

Last updated by the study team

2018-09-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Males or females, age 18 years or older.
• Relapsed or relapse/refractory MM with at least 1 prior line of therapy for phase 1 and 1 to 5 prior lines of therapy for phase 2.
• Patients with measurable disease defined as at least one of the following
• Serum M-protein ≥ 0.5 g/dl (≥ 5 g/l)
• Urine M-protein ≥ 200 mg/24 h
• Serum free light chains (FLC) assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/l) and an abnormal serum free light chain ratio (< 0.26 or > 1.65)
• Biopsy proven plasmacytoma. Prior biopsy is acceptable.
• If the serum protein electrophoresis is unreliable for routine M-protein measurement, quantitative immunoglobulin levels on nephrolometry or turbidometry will be followed.
• ECOG ≤ 2 OR Karnofsky ≥ 60%.
• Predose mean QTc≤ 450 msec or QTcF ≤ 450 msec.
• Negative pregnancy test for Females of childbearing potential.
• Voluntary, written informed consent.
• Ability to understand the purpose and risks of the study.
• Must be able to take and retain oral medications.
• Inclusion Clinical Laboratories Criteria
• Absolute neutrophil count (ANC) > 1,000 cells/dL (1.0 x 109/L)
• Platelet count > 50,000 cells/dL (50 x 109/L)
• Hemoglobin ≥ 8.0 g/dL (4.96 mmol/L)
• Serum AST or ALT ≤ 1.2 x ULN
• Total bilirubin within normal limits
• Creatinine clearance ≥ 30 mL/min
• Serum creatinine ≤ 1.5 x ULN
• Serum calcium (ionized or corrected for albumin) ≥ 2.0 mmol/L (8.0 mg/dL or 1.0 mmol/L ionized calcium) to ≤ 1.2 x ULN.
• Serum potassium, and magnesium within normal limits
• HgbA1c of ≤ 7%

You may not qualify if…

• Bortezomib refractory patients are not permitted on the Phase 2 part of the study.
• Diagnosed or treated for another malignancy within 3 years of enrollment, except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Patient has received other investigational drugs or chemotherapy within 21 days or approved anti-myeloma therapy within 14 days.
• History (within the last 6 months) of significant cardiovascular disease.
• Mean QTcF interval > 450 msec at screening.
• Prior autologous, peripheral stem cell transplant within 12 weeks of the first dose of study drug.
• Daily requirement for corticosteroids (except for inhalation corticosteroids).
• Patients with evidence of mucosal or internal bleeding and/or platelet transfusion refractory (i.e., unable to maintain a platelet count ≥ 50,000 cells/dL).
• Known active infection requiring parenteral or oral anti-infective treatment.
• Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation.
• Use of any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient.
• Patient has hypersensitivity to any of the components of study drugs.
• Known HIV or active hepatitis B or C viral infection.
• Diabetes mellitus currently requiring insulin or insulinotropic therapy or prior history of steroid induced diabetes.
• History of cerebrovascular accident (CVA) within 6 months prior to registration or that is not stable.
• Prior therapy with an IGF-1R inhibitor.
• Use of drugs that have a risk of causing QT interval prolongation and/or have a known risk of causing Torsades de Pointes (TdP) before 14 days or the recommended 5 half-life.
• Use of strong/moderate CYP1A2 inhibitors.
• Gastro-intestinal abnormalities that could affect the absorption of study drug.
• Peripheral neuropathy ≥ grade 2.
• Significant liver disease or metastatic disease to the liver
• History of amyloid, plasma cell leukemia or CNS involvement.
• Radiation therapy or major surgical procedure within 4 weeks of the first dose.

Where it is running

• Emory University Winship Cancer Institute — Atlanta, Georgia, United States
• University Of Chicago Medical Center — Chicago, Illinois, United States
• Queen Elizabeth II Health Sciences Center — Halifax, Nova Scotia, Canada
• University Health Network-Princess Margaret Hospital — Toronto, Ontario, Canada
• Hôpital Maisonneuve-Rosemont — Montreal, Quebec, Canada
• Sir Mortimer B. Davis-Jewish General Hospital — Montreal, Quebec, Canada

Full record on ClinicalTrials.gov

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