Multiple MyelomaPhase 1NCT01457417
A Study of DKN-01 in Multiple Myeloma or Advanced Solid Tumors
A Phase 1 study testing DKN-01 in people with Multiple Myeloma and Solid Tumors, run by Leap Therapeutics, Inc. at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Multiple Myeloma, Solid Tumors, Non-Small Cell Lung Cancer
- What is being tested?
- DKN-01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 8 sitesUnited States
- Study dates
- Jan 2012to Dec 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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)
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
New York Oncology Hematology, P.C.
Albany, New York, 12206
Texas Oncology - Baylor, Charles A. Sammonds Cancer Center
Dallas, Texas, 75246
Greenville Hospital System University Medical Center
Greenville, South Carolina, 29605
Virginia Oncology Associated
Norfolk, Virginia, 23502
Virginia Commonwealth University - Massey Cancer Center
Richmond, Virginia, 23298
Scottsdale Healthcare
Scottsdale, Arizona, 85258
Texas Oncology - Tyler
Tyler, Texas, 75702
Northwest Cancer Specialists, P.C.
Vancouver, Washington, 98684
About this study
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)
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.
Read the 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.
- Conditions
- Multiple Myeloma, Solid Tumors, Non-Small Cell Lung Cancer
- Being tested
- DKN-01
- Keywords
- Cancer, Oncology
- Medical subject headings
- Multiple Myeloma, Carcinoma, Non-Small-Cell Lung, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DKN-01Drug
Also called Formerly LY2812176
DKN-01 will be administered intravenously (IV) once a week over 30 minutes (min) and 2 hours (max) for 75, 150 and 300 mg. At 600 mg, DKN-01 will be administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: 3 participants will be treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation will occur sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching maximum tolerated dose (MTD) are met (or highest planned dose study group is completed). Cycle 1 will define the dose limiting toxicity (DLT) that governs dose escalation. PART B - Dose Confirmation: Once the MTD is established (or the highest planned dose level), 300 mg of DKN-01 will be administered IV on days 1 and 15 of every 28 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| 75 milligram (mg) DKN-01 Part A | Experimental | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle.
PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. Receives: Drug: DKN-01 |
| 150 mg DKN-01 Part A | Experimental | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle.
PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. Receives: Drug: DKN-01 |
| 300 mg DKN-01 Part A | Experimental | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle.
PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. Receives: Drug: DKN-01 |
| 600 mg DKN-01 Part A | Experimental | DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle.
PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. Receives: Drug: DKN-01 |
| 300 mg DKN-01 Part B | Experimental | Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle. Receives: Drug: DKN-01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Summary of Total Adverse Events (AE)
Total Adverse Events (AE), total treatment emergent adverse events (TEAE), total Serious Adverse Events (SAE), and total dose-limiting toxicity (DLT) for both Parts A and B.
Measured: Baseline to study completion (approximately 3 months)
Summary of Patients With Adverse Events (AE)
Number of patients who had Adverse Events (AE) including treatment related treatment emergent adverse events (TEAE), Common Toxicity Criteria for Adverse Effects (CTCAE), and Serious Adverse Events (SAE) for both Parts A and B. Severity was coded to NCI CTCAE version 4.02. For maximum severity and relationship, patients were counted only once in the most severe or most related category.
Measured: Baseline to study completion (approximately 3 months)
Progression Free Survival (PFS) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC)
For Part B only. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (ie, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation.
Measured: Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause
Secondary outcomes (8)
Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01
Area under the DKN-01 serum concentration-time profile curve during the dosing interval (AUC0-tau) after the first and fourth infusion for both Parts A and B. Cycle 1 Day 1 included once per week (QW) dosing groups and every two weeks (Q2W) dosing groups.
Measured: Cycle 1 Day 1 (first dose, all groups)
Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01
Area under the DKN-01 serum concentration-time profile curve during the dosing interval (AUC0-tau) after the first and fourth infusion for both Parts A and B. Cycle 1 day 22 included only QW dosing groups.
Measured: Cycle 1 Day 22 (Fourth Dose for QW)
Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01
Peak DKN-01 serum concentration (Cmax) after the first and fourth infusion on Cycle 1 Weeks 1 and 4, for both Parts A and B. Cycle 1 Day 1 included once per week (QW) dosing groups and every two weeks (Q2W) dosing groups.
Measured: Cycle 1 Day 1 (first dose, all groups)
Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01
Peak DKN-01 serum concentration (Cmax) after the fourth infusion on Cycle 1 Weeks 1 and 4, for both Parts A and B. Cycle 1 day 22 included only QW dosing groups.
Measured: Cycle 1 Day 22 (Fourth dose for QW groups)
Progression Free Survival (PFS) in Patients Who Are Refractory or Intolerant to Standard/Approved Therapies
For both Parts A and B. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (i.e, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation.
Measured: Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause
Overall Survival (OS) in Patients With Relapsed or Refractory NSCLC
For Part B only. OS was defined as the time from the date of signed informed consent to the date of death from any cause. For patients who were still alive as of the data cut-off date, OS time was censored on the date of the patient's last contact (last contact for patients in post-discontinuation was the last date of contact in long-term follow-up eCRF).
Measured: Time from the date of signed informed consent to the date of death from any cause
Objective Response Rate (ORR) in Oncologic Patients Who Are Refractory or Intolerant to Standard/Approved Therapies
For both Parts A and B. Objective response rate is defined as the number of patients with overall best response of complete response (CR) or partial response (PR)
Measured: Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter
Objective Response Rate (ORR) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC)
FAS : For both Parts A and B. Objective response rate is defined as the number of patients with overall best response of complete response (CR) or partial response (PR)
Measured: Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leap Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cyndi Sirard, MD, Study director, Heatlhcare Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01457417
- Sponsor's protocol ID
- P100
- Other IDs
- DEK-DKK1-P100, LY2812176
- Status last verified
- Sep 2016
- First submitted
- 18 Oct 2011
- Last updated
- 28 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01457417
- Acronym / sponsor ID
- P100
- Conditions
- Multiple Myeloma, Solid Tumors, Non-Small Cell Lung Cancer
- Keywords
- Cancer, Oncology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Leap Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 24 Oct 2011 (estimated)
- Results
- Posted 28 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 75 milligram (mg) DKN-01 Part A | Experimental | Drug: DKN-01DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| 150 mg DKN-01 Part A | Experimental | Drug: DKN-01DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| 300 mg DKN-01 Part A | Experimental | Drug: DKN-01DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| 600 mg DKN-01 Part A | Experimental | Drug: DKN-01DKN-01: DKN-01 was administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle. |
| 300 mg DKN-01 Part B | Experimental | Drug: DKN-01Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DKN-01Also: Formerly LY2812176DKN-01 will be administered intravenously (IV) once a week over 30 minutes (min) and 2 hours (max) for 75, 150 and 300 mg. At 600 mg, DKN-01 will be administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: 3 participants will be treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation will occur sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching maximum tolerated dose (MTD) are met (or highest planned dose study group is completed). Cycle 1 will define the dose limiting toxicity (DLT) that governs dose escalation. PART B - Dose Confirmation: Once the MTD is established (or the highest planned dose level), 300 mg of DKN-01 will be administered IV on days 1 and 15 of every 28 day cycle. | Drug | 150 mg DKN-01 Part A, 300 mg DKN-01 Part A, 300 mg DKN-01 Part B, 600 mg DKN-01 Part A, 75 milligram (mg) DKN-01 Part A |
Primary outcome
Summary of Total Adverse Events (AE)
Time frame: Baseline to study completion (approximately 3 months)
Total Adverse Events (AE), total treatment emergent adverse events (TEAE), total Serious Adverse Events (SAE), and total dose-limiting toxicity (DLT) for both Parts A and B.
Summary of Patients With Adverse Events (AE)
Time frame: Baseline to study completion (approximately 3 months)
Number of patients who had Adverse Events (AE) including treatment related treatment emergent adverse events (TEAE), Common Toxicity Criteria for Adverse Effects (CTCAE), and Serious Adverse Events (SAE) for both Parts A and B. Severity was coded to NCI CTCAE version 4.02. For maximum severity and relationship, patients were counted only once in the most severe or most related category.
Progression Free Survival (PFS) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC)
Time frame: Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause
For Part B only. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (ie, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation.
8 secondary outcomes
Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01
Time frame: Cycle 1 Day 1 (first dose, all groups)
Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01
Time frame: Cycle 1 Day 22 (Fourth Dose for QW)
Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01
Time frame: Cycle 1 Day 1 (first dose, all groups)
Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01
Time frame: Cycle 1 Day 22 (Fourth dose for QW groups)
Progression Free Survival (PFS) in Patients Who Are Refractory or Intolerant to Standard/Approved Therapies
Time frame: Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause
Overall Survival (OS) in Patients With Relapsed or Refractory NSCLC
Time frame: Time from the date of signed informed consent to the date of death from any cause
Objective Response Rate (ORR) in Oncologic Patients Who Are Refractory or Intolerant to Standard/Approved Therapies
Time frame: Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter
Objective Response Rate (ORR) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC)
Time frame: Part A: Every 2 months; Part B: after 1 month and every two cycles thereafter
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cyndi Sirard, MD study director
Heatlhcare Pharmaceuticals
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DKN-01 in people with Multiple Myeloma and Solid Tumors, run by Leap Therapeutics, Inc. at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Summary of Total Adverse Events (AE) (time frame: Baseline to study completion (approximately 3 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2016.