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

NCT01672736 | Terminated Phase 1 Results DMC

• 1 other identifier: PMHOSI906-MM001
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 6

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

Relapsed or relapse/refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of the Combination of ASP7487 (OSI-906) With Velcade and Dexamethasone

  * Phase 1: To determine the maximum tolerated dose (MTD) of ASP7487 (OSI-906) administered in combination with the recommended dose and schedule of bortezomib and dexamethasone; * Phase 2: To evaluate the antitumor activity of ASP7487 (OSI-906) in combination with bortezomib and dexamethasone at the MTD established from the Phase 1 component.

  45 months

Study Arms (1)

ASP7487, Velcade, Dexamethasone

EXPERIMENTAL

ASP7487 administered orally 75, 100 and 150 mg) BID continuously for each cycle. Bortezomib administered at 1.3 mg/m2 twice weekly for the first 8 21 day cycles and once weekly beyond cycle 9 for 35 day cycles. Dexamethasone is administered on bortezomib administration days at 20 mg

Drug: ASP7487, Velcade, Dexamethasone

Interventions

ASP7487, Velcade, Dexamethasone DRUG

ASP7487- Oral (75, 100, 150 mg)BID Bortezomib- 1.3 mg/m2 IV on days 1, 4, 8, 15 of each 21 day cycle up to cycle 8 and days 1, 5, 15, 22 of each 35 day cycle beyond cycle 9 Dexamethasone- 20 mg on the day of Bortezomib administration

Also known as: ASP7487, Bortezomib, Dexamethasone

ASP7487, Velcade, Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.
• Absolute neutrophil count (ANC) \> 1,000 cells/dL (1.0 x 109/L)

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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Multiple Myeloma Research Consortium: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (6)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University Of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Queen Elizabeth II Health Sciences Center

Halifax, Nova Scotia, B3H2Y9, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Sir Mortimer B. Davis-Jewish General Hospital

Montreal, Quebec, H3T 1E3, Canada

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

Patient enrollment was stopped prematurely due to the drug manufacturer's decision to terminate the development of the study drug, Linsitinib. The study did not proceed to Phase II portion of the study protocol.

Results Point of Contact

• Title: Dr. Suzanne Trudel
• Organization: University Health Network - Princess Margaret Cancer Centre

Suzanne.Trudel@uhn.ca

416-946-4501

Study Officials

• Suzanne Trudel, MD

  UHN-PMH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2012
• First Posted: August 27, 2012
• Study Start: September 1, 2012
• Primary Completion: March 27, 2017
• Study Completion: December 27, 2017
• Last Updated: September 13, 2018
• Results First Posted: September 13, 2018

Record last verified: 2018-09

Locations

US (2); CA (4)