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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Multiple Myeloma Research Consortium
Astellas Pharma Inc
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01672736
First received: August 1, 2012
Last updated: December 2, 2015
Last verified: December 2015
  Purpose
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.

Condition Intervention Phase
Multiple Myeloma
Drug: ASP7487, Velcade, Dexamethasone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Trial of ASP7487 OSI-906)in Combination With Bortezomib and Dexamethasone for the Treatment of Relapsed or Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Maximum Tolerated Dose of the combination of ASP7487 (OSI-906) with Velcade and Dexamethasone [ Time Frame: It is estimated that it will take approximately 3-5 months determine MTD. The efficacy analysis could take upto 2.5 years after the activation date of the study to be completed. ] [ Designated as safety issue: Yes ]
    • 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.


Estimated Enrollment: 75
Study Start Date: September 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ASP7487, Velcade, Dexamethasone
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
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
Other Names:
  • ASP7487
  • Bortezomib
  • Dexamethasone

Detailed Description:
The Phase 1 portion of the study will determine the MTD and DLTs of bortezomib administered on days 1, 4, 8 and 11 of a 21-day cycle combined with ASP7487 (OSI-906) dosed twice daily orally continuously. The combination of ASP7487 (OSI-906) with bortezomib has not previously been tested. The active agent bortezomib will be used during Cycle 1 - 8 at the recommended treatment dose of 1.3 mg/m2 days 1, 4, 8 and 11 and Cycles 9+ on days 1, 8, 15 and 22 of a 5-week cycle and ASP7487 (OSI-906) will be dose escalated form 75 mg to 150mg utilizing 3+3 design
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Males or females, age 18 years or older.
  2. 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.
  3. Patients with measurable disease defined as at least one of the following

    1. Serum M-protein ≥ 0.5 g/dl (≥ 5 g/l)
    2. Urine M-protein ≥ 200 mg/24 h
    3. 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)
    4. Biopsy proven plasmacytoma. Prior biopsy is acceptable.
    5. If the serum protein electrophoresis is unreliable for routine M-protein measurement, quantitative immunoglobulin levels on nephrolometry or turbidometry will be followed.
  4. ECOG ≤ 2 OR Karnofsky ≥ 60%.
  5. Predose mean QTc≤ 450 msec or QTcF ≤ 450 msec.
  6. Negative pregnancy test for Females of childbearing potential.
  7. Voluntary, written informed consent.
  8. Ability to understand the purpose and risks of the study.
  9. Must be able to take and retain oral medications.
  10. Inclusion Clinical Laboratories Criteria

    1. Absolute neutrophil count (ANC) > 1,000 cells/dL (1.0 x 109/L)
    2. Platelet count > 50,000 cells/dL (50 x 109/L)
    3. Hemoglobin ≥ 8.0 g/dL (4.96 mmol/L)
    4. Serum AST or ALT ≤ 1.2 x ULN
    5. Total bilirubin within normal limits
    6. Creatinine clearance ≥ 30 mL/min
    7. Serum creatinine ≤ 1.5 x ULN
    8. 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.
    9. Serum potassium, and magnesium within normal limits
    10. HgbA1c of ≤ 7%
    11. Troponin I or T within normal limits
    12. BNP or NT-proBNP within normal limits
    13. Fasting glucose of ≤126 mg/dL (7.0 mmol/L).
  11. Resolution of prior treatment associated toxicities to ≤ grade 1

Exclusion Criteria

  1. Bortezomib refractory patients are not permitted on the Phase 2 part of the study.
  2. 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.
  3. Patient has received other investigational drugs or chemotherapy within 21 days or approved anti-myeloma therapy within 14 days.
  4. History (within the last 6 months) of significant cardiovascular disease.
  5. Mean QTcF interval > 450 msec at screening.
  6. Prior autologous, peripheral stem cell transplant within 12 weeks of the first dose of study drug.
  7. Daily requirement for corticosteroids (except for inhalation corticosteroids).
  8. 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).
  9. Known active infection requiring parenteral or oral anti-infective treatment.
  10. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation.
  11. Use of any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient.
  12. Patient has hypersensitivity to any of the components of study drugs.
  13. Known HIV or active hepatitis B or C viral infection.
  14. Diabetes mellitus currently requiring insulin or insulinotropic therapy or prior history of steroid induced diabetes.
  15. History of cerebrovascular accident (CVA) within 6 months prior to registration or that is not stable.
  16. Prior therapy with an IGF-1R inhibitor.
  17. 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.
  18. Use of strong/moderate CYP1A2 inhibitors.
  19. Gastro-intestinal abnormalities that could affect the absorption of study drug.
  20. Peripheral neuropathy ≥ grade 2.
  21. Significant liver disease or metastatic disease to the liver
  22. History of amyloid, plasma cell leukemia or CNS involvement.
  23. Radiation therapy or major surgical procedure within 4 weeks of the first dose.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01672736

Locations
United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Illinois
University Of Chicago Medical Center
Chicago, Illinois, United States, 60637
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Center
Halifax, Nova Scotia, Canada, B3H2Y9
Canada, Ontario
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T 2M4
Sir Mortimer B. Davis-Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E3
Sponsors and Collaborators
University Health Network, Toronto
Multiple Myeloma Research Consortium
Astellas Pharma Inc
Investigators
Principal Investigator: Suzanne Trudel, MD UHN-PMH
  More Information

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01672736     History of Changes
Other Study ID Numbers: PMHOSI906-MM001 
Study First Received: August 1, 2012
Last Updated: December 2, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Relapsed or relapse/refractory Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 30, 2016