This study is designed to assess the efficacy and safety of filanesib + carfilzomib versus single-agent carfilzomib in patients with multiple myeloma who have received at least 2 prior lines of therapy.

• Register: EUCTR
• Last refreshed on: 12 October 2015
• Main ID: EUCTR2014-001052-39-ES
• Date of registration: 22/09/2014
• Prospective Registration: Yes
• Primary sponsor: Array BioPharma Inc.
• Public title: This study is designed to assess the efficacy and safety of filanesib + carfilzomib versus single-agent carfilzomib in patients with multiple myeloma who have received at least 2 prior lines of therapy.
• Scientific title: The FACTOR Study (Filanesib and Carfilzomib Treatment of Relapsed/Refractory Multiple Myeloma): A Multinational, Randomized, Open-label Phase 3 Study of Filanesib (ARRY-520) + Carfilzomib Versus Single-agent Carfilzomib in Patients With Advanced Multiple Myeloma
• Date of first enrolment: 03/11/2014
• Target sample size: 552
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001052-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Belgium, Canada, Czech Republic, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Dra. Laura Rosiñol Dachs
• Affiliation: Hospital Clinic de Barcelona

• Name: Dra. Laura Rosiñol Dachs
• Affiliation: Hospital Clinic de Barcelona

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provide a personally signed and dated informed consent form prior to initiation of any study-related procedures or assessments that are not considered standard of care.
2. Male or female ? 18 years of age at time of informed consent.
3. Patients with confirmed multiple myeloma whose treatment history must include both of
the following:
a. Received at least 2 and no more than 6 prior lines of treatment, including a bortezomib-containing regimen and an IMiD-containing regimen (i.e., lenalidomide, thalidomide, pomalidomide). Induction therapy and stem cell transplant ± maintenance are to be considered a single line of therapy.
b. Disease refractory to the last myeloma therapy, defined as development of PD per IMWG criteria while on therapy or within 60 days from last dose of therapy.
4. Measurable multiple myeloma disease, defined as meeting at least 1 of the following criteria within 14 days prior to randomization:
a. A monoclonal Ig (M-protein) concentration on serum protein electrophoresis (SPEP) of ? 1.0 g/dL.
b. Measurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of ? 200 mg/24 hours.
c. Involved serum free light chain (FLC) level ? 10 mg/dL, provided the serum FLC ratio is abnormal.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to randomization.
6. Adequate hematology laboratory values within 14 days prior to randomization:
a. Neutrophils ? 1.5 × 109/L without growth factor support (defined as no growth factor administration for at least 14 days prior to observation). If the bone marrow contains ? 50% plasma cells, a neutrophil count of ? 1.0 × 109/L is allowed.
b. Platelets ? 75 × 109/L without transfusion support (defined as no platelet transfusions for at least 3 days prior to observation). If the bone marrow contains ? 50% plasma cells, a platelet count of ? 50 × 109/L is allowed.
7. Adequate hepatic and renal function laboratory values within 14 days prior to randomization:
a. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ? 3 × ULN.
b. Total bilirubin ? 1.5 mg/dL.
c. Calculated (Cockcroft and Gault formula) or measured creatinine clearance ? 25 mL/min.
8. Left ventricular ejection fraction (LVEF) ? 40% within 28 days prior to randomization, evaluated by 2-D transthoracic echocardiogram (ECHO) or, if ECHO is not available, by multi-gated acquisition (MUGA) scan.
9. If patient is a woman of childbearing potential, she must have a negative serum beta human chorionic gonadotropin (?-HCG) test within 14 days prior to randomization and consent to ongoing pregnancy testing during the course of the study.
10. Male patients must agree to use a highly effective method of contraception through 90 days after the last administration of study drug and women of childbearing potential must agree to use a highly effective method of contraception through 30 days after the last administration of study drug.
11. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 184
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 368

Exclusion criteria:
1. Prior treatment with filanesib (ARRY-520) or any other KSP inhibitor.
2. Prior treatment with carfilzomib unless treatment was part of induction therapy (first line after diagnosis) that resulted in a response of PR or better, the patient tolerated carfilzomib treatment (did not discontinue treatment due to toxicity), and there has been at least a 6-month carfilzomib treatment-free interval prior to randomization.
3. Prior participation in a Phase 3 clinical study of carfilzomib, regardless of treatment(s) received.
4. Past or current plasma cell leukemia (> 2 × 109/L circulating plasma cells and plasma cells accounting for ? 20% by any means of white blood cell [WBC] differential).
5. Primary amyloidosis (amyloidosis associated with multiple myeloma is allowed).
6. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes).
7. Ongoing Grade 3 or Grade 4 peripheral neuropathy (per NCI CTCAE, Version 4.03), 24 or Grade 2 peripheral neuropathy with pain despite appropriate interventions, within 28 days prior to randomization.
8. Autologous or allogeneic stem cell or bone marrow transplant within 3 months prior to randomization.
9. Concomitant malignancies or previous malignancies (other than multiple myeloma) with less than a 2-year disease-free interval at the time of randomization. Patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or Stage 1 prostate cancer are eligible irrespective of the time of
diagnosis.
10. Use of an investigational agent that is not expected to be cleared by the time of
randomization or that has demonstrated prolonged side effects. Patients must have
recovered from the side effects to Grade 0 or Grade 1 (except alopecia [any grade is
allowed] and neuropathy [see exclusion criterion #6]).
11. Monoclonal antibody treatment for multiple myeloma within 28 days prior to randomization.
12. Cytotoxic therapy within 21 days prior to randomization.
13. Proteasome inhibitor therapy within 14 days prior to randomization.
14. Immunomodulatory agent therapy within 7 days prior to randomization.
15. Radiotherapy within 21 days prior to randomization. However, if the radiation portal covers ? 5% of the bone marrow reserve, the patient is eligible irrespective of the end date of radiotherapy.
16. Corticosteroid doses > 10 mg/day of prednisone or equivalent within 14 days prior to randomization.
17. History of allergic reaction/hypersensitivity to any of the study medications, their analogues, or excipients in the various formulations.
18. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
19. Contraindication to any of the required concomitant drugs (including dexamethasone and filgrastim) or supportive treatments, antiviral drugs, or intolerance to hydration due to pre-existing pulmonary, cardiac or renal impairment.
20. Any major surgery where adequate wound healing has not occurred prior to randomization.
21. Medical, psychiatric or other conditions that may interfere with patient safety or compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol, or to complete the study.
22. Known pulmonary hypertension of any severity.
23. Concurrent cardiac disease (including symptomatic congestive heart failure [New York Heart Association Class III or IV], symptomatic cardiac ischemia, unstable angina pe

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Multiple Myeloma
MedDRA version: 17.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Intervention(s)

Product Name: Filanesib
Product Code: ARRY-520
Pharmaceutical Form: Powder for concentrate for solution for injection/infusion
INN or Proposed INN: filanesib
CAS Number: 885060-09-3
Current Sponsor code: ARRY-520
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1.0-

Trade Name: Kyprolis
Product Name: Carfilzomib
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: carfilzomib
CAS Number: 868540-17-4
Other descriptive name: CARFILZOMIB
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Secondary Objective: ? Evaluate additional measures of efficacy in patients treated with carfilzomib + filanesib and single-agent carfilzomib for the entire population, for patients with low serum AAG levels at Baseline and for patients with high serum AAG levels at Baseline
? Evaluate the utility of serum AAG level at Baseline as a prognostic biomarker and as a predictive biomarker for clinical outcomes
? Compare the safety of carfilzomib + filanesib treatment and single-agent carfilzomib treatment
? Measure plasma concentrations of filanesib and determine model-based pharmacokinetic (PK) parameters in patients randomized to receive carfilzomib + filanesib

Main Objective: Co-primary:
? Compare progression-free survival (PFS) in patients treated with carfilzomib + filanesib and single-agent carfilzomib
? Compare objective response rates (ORR) in patients with low serum alpha 1-acid glycoprotein (AAG) levels at Baseline treated with carfilzomib + filanesib and single-agent carfilzomib

Primary end point(s): Co-primary:
? PFS in the entire population
? ORR, defined as the percentage of patients achieving an objective response of partial response (PR) or better, in patients with low serum AAG levels at Baseline

Timepoint(s) of evaluation of this end point: Patients may continue receiving treatment with carfilzomib ± filanesib in 28-day cycles as long as none of the treatment discontinuation criteria are met. Disease evaluations will be conducted on Day 1 (+/-4 days) of each cycle.

Secondary Outcome(s)

Secondary end point(s): Secondary:
? PFS in patients with low serum AAG levels at Baseline and in patients with high serum AAG levels at Baseline
? ORR in the entire population and in patients with high serum AAG levels at Baseline

In the entire population, in patients with low serum AAG levels at Baseline and in patients with high serum AAG levels at Baseline:
? Duration of response (DOR)
? Time to response
? Clinical benefit rate, defined as ORR + minimal response (MR)
? Overall survival (OS)
? Incidence, relatedness and severity of adverse events (AEs), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03
? Change in clinical laboratory parameters
? Change in electrocardiogram (ECG) parameters
? Plasma concentrations and model-based PK parameter estimates for
filanesib

Timepoint(s) of evaluation of this end point: Patients may continue receiving treatment with carfilzomib ± filanesib in 28-day cycles as long as none of the treatment discontinuation criteria are met. Disease evaluations will be conducted on Day 1 (+/-4 days) of each cycle.

Secondary ID(s)

2014-001052-39-SE

ARRAY-520-311

Source(s) of Monetary Support

Array BioPharma Inc.