Clinical trial NCT01457417: A Study of DKN-01 in Multiple Myeloma or Advanced Solid Tumors
Official title: A Two Part Phase 1 Multicenter Open-label Study of DKN-01 Given Intravenously. Part A: Dose-Escalation in Patients With Multiple Myeloma or Advanced Solid Tumors. Part B: Expansion Cohort in Patients With Relapsed / Refractory Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Solid Tumors
Non-Small Cell Lung Cancer
Keywords: Cancer
Oncology
Lead sponsor: Leap Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2011-10-24
Enrollment: 32
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to characterize the safety and toxicity of DKN-01 by determining a maximum-tolerated dose and associated dose limiting toxicity. To evaluate the pharmacodynamic response in patients with cancer. To characterize the pharmacokinetic parameters of DKN-01 in cancer patients who are intolerant to standard/approved therapies.

Detailed description: Part A of this trial consists of 4 treatment arms of DKN-01. It is a dose escalation study in patients with multiple myeloma or advanced solid tumors. Patients must be refractory or intolerant to all standard/approved therapy(ies). At each dose level, 3 subjects will be treated. If none of the 3 subjects develop a dose limiting toxicity after a minimum of 4 weeks of treatment, subsequent dose escalation will proceed according to the same schedule. Part B consists of dose confirmation in patients with NSCLC. Patients must be refractory or intolerant to all standard/approved therapy(ies). Approximately 15 patients may be enrolled in Part B.

Eligibility criteria: Inclusion Criteria:

Part A: Patients with histological or cytological confirmed multiple myeloma or advanced solid tumors. For multiple myeloma, must have symptomatic myeloma as defined by the International Myeloma Working Group inclusive of measurable serum and/or urine monoclonal protein (M-protein) or for those without elevations they must have measurable increased concentrations of free light chains

Part B: Patients with previously treated, histologically confirmed advanced NSCLC with progressive disease requiring therapy

Parts A and B:

* Refractory or intolerant to all standard/approved therapy(ies)
* Patients with solid tumors must have one or more metastatic tumors measurable on computed tomography (CT) scan using Response Evaluation Criteria in Solid Tumors (RECIST) criteria
* Radiation for symptomatic lesions outside the central nervous system (CNS) must have been completed at least 2 week prior to study enrollment
* Treated brain metastases will be allowed, if they are asymptomatic. Patients must be off corticosteroids for at least 2 week prior to study entry
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1
* Life expectancy of at least 3 months
* Ambulatory patients greater than or equal to (≥) 30 years of age
* Females with child bearing potential must have a negative serum pregnancy test within 7 days of study entry
* Acceptable liver function, renal function, hematologic status
* Urinalysis - No clinically significant abnormalities
* Acceptable coagulation status:

  * Prothrombin Time/Partial Thromboplastin Time (PT/PTT) ≤ 1.2 x upper limit of normal (ULN) (unless receiving anticoagulation therapy - eligibility based upon INR)
  * International Normalization Ratio (INR) ≤ 1.6 (unless receiving anticoagulant therapy)

    * Receiving warfarin; INR ≤ 3.0 and no active bleeding
* For men and women of child-producing potential, the use of effective contraceptive methods during the study and for women 18 months following the last dose of study drug
* Available for the study duration and willing to follow procedures
* Serum calcium:

  * Solid tumors only: within normal limits
  * Multiple myeloma: ≤ 11.5 milligrams per deciliter (mg/dL)

Exclusion Criteria:

* History of osteonecrosis of the hip or evidence of structural bone abnormalities in the proximal femur on magnetic resonance imaging (MRI) scan considered clinically significant or may impact the interpretation of the scan. Degenerative changes of the hip joint are not exclusionary
* Unable to tolerate the confinement/noise of an MRI scanner or have any contraindication for MRI
* New York Heart Association Class 3 or 4, cardiac disease, myocardial infarction, unstable arrhythmia, or evidence of ischemia
* Have Fridericia-corrected QT interval (QTcF) \> 470 millisecond (msec) (female) or \> 450 (male), or history of congenital long QT syndrome.
* Active, uncontrolled bacterial, viral, or fungal infections
* Pregnant or nursing women
* Radiation therapy, surgery, or chemotherapy, within 1 month prior to study entry
* Previously treated with an anti-Dickkopf-related protein 1 (DKK-1) therapy
* Significant allergy to a biological pharmaceutical therapy
* History of major organ transplant
* Had an autologous or allogenic bone marrow transplant, current acute leukemia, colon, prostate, breast or small cell lung cancer, osteoblastic lesions, concomitant disease known to influence calcium metabolism including hyperparathyroidism, hyperthyroidism and/or Paget's disease of bone
* Unwillingness / inability to comply with procedures
* Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
* Serious nonmalignant disease
* Receiving other investigational agent or have received other investigational agent within last 30 days or 5 half-lives, whichever is longer
* Receiving lithium chloride (LiCl)

Primary outcomes:
measure: Summary of Total Adverse Events (AE)
timeFrame: Baseline to study completion (approximately 3 months)
measure: Summary of Patients With Adverse Events (AE)
timeFrame: Baseline to study completion (approximately 3 months)
measure: Progression Free Survival (PFS) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC)
timeFrame: Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause
Secondary outcomes:
measure: Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01
timeFrame: Cycle 1 Day 1 (first dose, all groups)
measure: Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01
timeFrame: Cycle 1 Day 22 (Fourth Dose for QW)
measure: Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01
timeFrame: Cycle 1 Day 1 (first dose, all groups)
measure: Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01
timeFrame: Cycle 1 Day 22 (Fourth dose for QW groups)
measure: Progression Free Survival (PFS) in Patients Who Are Refractory or Intolerant to Standard/Approved Therapies
timeFrame: Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause
measure: Overall Survival (OS) in Patients With Relapsed or Refractory NSCLC
timeFrame: Time from the date of signed informed consent to the date of death from any cause
measure: Objective Response Rate (ORR) in Oncologic Patients Who Are Refractory or Intolerant to Standard/Approved Therapies
timeFrame: Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter
measure: Objective Response Rate (ORR) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC)
timeFrame: Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare
state: Arizona
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Greenville
country: United States
facility: Greenville Hospital System University Medical Center
state: South Carolina
city: Dallas
country: United States
facility: Texas Oncology - Baylor, Charles A. Sammonds Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associated
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University - Massey Cancer Center
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
Study officials:
affiliation: Heatlhcare Pharmaceuticals
name: Cyndi Sirard, MD
role: STUDY_DIRECTOR
References: