search
Back to results

A Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma

Primary Purpose

Melanoma

Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
PLX3397
Sponsored by
Daiichi Sankyo Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring PLX3397, Kit-mutant Melanoma, Unresectable or Metastatic KIT-mutated Melanoma, Developmental Phase I/II

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years
  • Unresectable stage III or stage IV melanoma which is histologically confirmed at the treating institution with KIT mutation(s) not known to be resistant to PLX3397
  • Presence of measurable lesions by Response Evaluation Criteria in Solid Tumors
  • Eastern Cooperative Oncology Group (ECOG) performance Status (PS) 0-2
  • Life expectancy ≥ 3 months
  • Adequate organ and bone marrow function
  • Women of child-bearing potential must have a negative serum pregnancy test at Screening and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study drug. Women of non-child-bearing potential must have been postmenopausal for ≥ 1 year or surgically sterile.
  • Fertile men must agree to use an effective method of birth control during the study and for up to 3 months after the last dose of study drug.
  • Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements

Exclusion Criteria:

  • Prior treatment with a KIT inhibitor for melanoma
  • Presence of NRAS or BRAF mutation
  • Exposure to any investigational drug within 28 days or unresolved adverse effects from previous therapy
  • Symptomatic brain metastases.
  • Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Sponsor
  • Concomitant treatment with other anti-neoplastic agents (hormonal therapy acceptable)
  • Uncontrolled intercurrent or infectious illness
  • Major surgical procedure or significant traumatic injury within 14 days of initiating study drug or anticipation of the need for major surgery during the study
  • Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy within 28 days prior to study entry
  • Inability to swallow capsules, or refractory nausea and vomiting, malabsorption, an external biliary shunt, or significant bowel resection that would preclude adequate absorption
  • Congestive heart failure (CHF) New York (NY) Heart Association class III or IV; unstable coronary artery disease [myocardial infarction (MI) more than 6 months prior to study entry is permitted] or serious cardiac arrhythmia
  • Baseline QT interval corrected using Fridericia equation (QTcF) ≥ 450 msec (for males) or ≥ 470 msec (for females) at Screening
  • Active or chronic infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV)
  • Known chronic liver disease
  • Women who are breast-feeding or pregnant

Sites / Locations

  • Beijing Cancer Hospital
  • Sun Yat-sen Hospital
  • Samsung Medical Center
  • Severance Hospital, Yonsei University Health System
  • Seoul National University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PLX3397

Arm Description

Part 1: Open label, multicenter study includes a dose evaluation portion in which the safety profile of PLX3397 as a single oral agent will be evaluated Part 2: An expansion cohort in which the efficacy and safety of PLX3397 administered at the recommended Phase 2 dose will be evaluated in patients with unresectable stage III or stage IV KIT-mutated melanoma.

Outcomes

Primary Outcome Measures

Summary of Best Overall Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
For the assessment of best overall response, participants were classified by RECIST v1.1: complete response (CR), disappearance of all target lesions and normalization of tumor marker level; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; stable disease (SD); neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study; progressive disease (PD), at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm; or not evaluable (NE) for analysis.
Objective Response Rate (ORR) Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Objective response rate was defined as complete response (CR) or partial response (PR).

Secondary Outcome Measures

Duration of Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Duration of Response (DoR) was defined as the time from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the first documentation of disease progression or to death due to any cause, whichever occurred first. DoR was to only be calculated for the subgroup of participants with an objective tumor response.
Progression-free Survival Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Progression-free survival (PFS) was to be calculated for each participant as the number of days from study enrollment to the date of the first documented disease progression or date of death from any cause, whichever occurred first.
Overall Survival Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Overall survival (OS) was defined as the time from study enrollment to death from any cause, censoring at the date of last contact or the end of the study.
Disease Control Rate Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Disease control rate (DCR) was defined as the percentage of participants who had achieved complete response (CR), partial response (PR), or stable disease (SD).
Summary of Pharmacokinetic Parameter of Maximum Concentration (Cmax) of PL3397 at Days 1 and 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma
Summary of Pharmacokinetic Parameter of Area Under the Curve From Zero to 6 Hours (AUC0-6) of PL3397 at Days 1 and 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma
Summary of Pharmacokinetic Parameter of Time to Maximum Concentration and Last Measurable Time of PL3397 at Days 1 and 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma
Summary of Pharmacokinetic Parameter of Accumulation Ratio of Day 15 to Day 1 for AUC0-6h (Robs) of PL3397 at Day 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma
Summary of Pharmacokinetic Parameter of Accumulation Ratio of Day 15 to Day 1 for Cmax (Rcmax) of PL3397 at Day 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma
Summary of Most Common (≥50% of Participants) Treatment-emergent Adverse Events Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Summary of Treatment-emergent Adverse Events Grade ≥ 3 Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Grade ≥ 3 was used to indicate moderate-to-severe treatment-emergent adverse events in which moderate was defined as discomfort enough to cause interference with normal daily activities and severe defined as the inability to perform normal daily activities.
Summary of Most Common (≥50%) Drug-related Treatment-emergent Adverse Events Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Summary of Drug-related Treatment-emergent Adverse Events Grade ≥ 3 Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Grade ≥ 3 was used to indicate moderate-to-severe treatment-emergent adverse events in which moderate was defined as discomfort enough to cause interference with normal daily activities and severe defined as the inability to perform normal daily activities.

Full Information

First Posted
November 21, 2016
Last Updated
May 8, 2023
Sponsor
Daiichi Sankyo Co., Ltd.
Collaborators
Daiichi Sankyo, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT02975700
Brief Title
A Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma
Official Title
A Phase I/II Open Label, Multicenter Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2017 (undefined)
Primary Completion Date
August 31, 2018 (Actual)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo Co., Ltd.
Collaborators
Daiichi Sankyo, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this Phase I/II study is to evaluate safety, pharmacokinetics, and preliminary efficacy of the investigational drug PLX3397 in subjects with unresectable or metastatic KIT-mutated melanoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
PLX3397, Kit-mutant Melanoma, Unresectable or Metastatic KIT-mutated Melanoma, Developmental Phase I/II

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PLX3397
Arm Type
Experimental
Arm Description
Part 1: Open label, multicenter study includes a dose evaluation portion in which the safety profile of PLX3397 as a single oral agent will be evaluated Part 2: An expansion cohort in which the efficacy and safety of PLX3397 administered at the recommended Phase 2 dose will be evaluated in patients with unresectable stage III or stage IV KIT-mutated melanoma.
Intervention Type
Drug
Intervention Name(s)
PLX3397
Other Intervention Name(s)
Pexidartinib
Primary Outcome Measure Information:
Title
Summary of Best Overall Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description
For the assessment of best overall response, participants were classified by RECIST v1.1: complete response (CR), disappearance of all target lesions and normalization of tumor marker level; partial response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; stable disease (SD); neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study; progressive disease (PD), at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm; or not evaluable (NE) for analysis.
Time Frame
within 18 months postdose
Title
Objective Response Rate (ORR) Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description
Objective response rate was defined as complete response (CR) or partial response (PR).
Time Frame
within 18 months postdose
Secondary Outcome Measure Information:
Title
Duration of Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description
Duration of Response (DoR) was defined as the time from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the first documentation of disease progression or to death due to any cause, whichever occurred first. DoR was to only be calculated for the subgroup of participants with an objective tumor response.
Time Frame
within 18 months postdose
Title
Progression-free Survival Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description
Progression-free survival (PFS) was to be calculated for each participant as the number of days from study enrollment to the date of the first documented disease progression or date of death from any cause, whichever occurred first.
Time Frame
within 18 months postdose
Title
Overall Survival Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description
Overall survival (OS) was defined as the time from study enrollment to death from any cause, censoring at the date of last contact or the end of the study.
Time Frame
within 18 months postdose
Title
Disease Control Rate Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description
Disease control rate (DCR) was defined as the percentage of participants who had achieved complete response (CR), partial response (PR), or stable disease (SD).
Time Frame
within 18 months postdose
Title
Summary of Pharmacokinetic Parameter of Maximum Concentration (Cmax) of PL3397 at Days 1 and 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma
Time Frame
Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose
Title
Summary of Pharmacokinetic Parameter of Area Under the Curve From Zero to 6 Hours (AUC0-6) of PL3397 at Days 1 and 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma
Time Frame
Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose
Title
Summary of Pharmacokinetic Parameter of Time to Maximum Concentration and Last Measurable Time of PL3397 at Days 1 and 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma
Time Frame
Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose
Title
Summary of Pharmacokinetic Parameter of Accumulation Ratio of Day 15 to Day 1 for AUC0-6h (Robs) of PL3397 at Day 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma
Time Frame
Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose
Title
Summary of Pharmacokinetic Parameter of Accumulation Ratio of Day 15 to Day 1 for Cmax (Rcmax) of PL3397 at Day 15 Following Twice Daily Administration of PL3397 at 1000 mg/Day in Participants With Unresectable or Advanced KIT-mutated Melanoma
Time Frame
Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose
Title
Summary of Most Common (≥50% of Participants) Treatment-emergent Adverse Events Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Time Frame
within 28 days after administration of the last dose of study drug, up to 18 months postdose
Title
Summary of Treatment-emergent Adverse Events Grade ≥ 3 Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description
Grade ≥ 3 was used to indicate moderate-to-severe treatment-emergent adverse events in which moderate was defined as discomfort enough to cause interference with normal daily activities and severe defined as the inability to perform normal daily activities.
Time Frame
within 28 days after administration of the last dose of study drug, up to 18 months postdose
Title
Summary of Most Common (≥50%) Drug-related Treatment-emergent Adverse Events Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Time Frame
within 28 days after administration of the last dose of study drug, up to 18 months postdose
Title
Summary of Drug-related Treatment-emergent Adverse Events Grade ≥ 3 Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
Description
Grade ≥ 3 was used to indicate moderate-to-severe treatment-emergent adverse events in which moderate was defined as discomfort enough to cause interference with normal daily activities and severe defined as the inability to perform normal daily activities.
Time Frame
within 28 days after administration of the last dose of study drug, up to 18 months postdose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years Unresectable stage III or stage IV melanoma which is histologically confirmed at the treating institution with KIT mutation(s) not known to be resistant to PLX3397 Presence of measurable lesions by Response Evaluation Criteria in Solid Tumors Eastern Cooperative Oncology Group (ECOG) performance Status (PS) 0-2 Life expectancy ≥ 3 months Adequate organ and bone marrow function Women of child-bearing potential must have a negative serum pregnancy test at Screening and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study drug. Women of non-child-bearing potential must have been postmenopausal for ≥ 1 year or surgically sterile. Fertile men must agree to use an effective method of birth control during the study and for up to 3 months after the last dose of study drug. Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements Exclusion Criteria: Prior treatment with a KIT inhibitor for melanoma Presence of NRAS or BRAF mutation Exposure to any investigational drug within 28 days or unresolved adverse effects from previous therapy Symptomatic brain metastases. Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Sponsor Concomitant treatment with other anti-neoplastic agents (hormonal therapy acceptable) Uncontrolled intercurrent or infectious illness Major surgical procedure or significant traumatic injury within 14 days of initiating study drug or anticipation of the need for major surgery during the study Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy within 28 days prior to study entry Inability to swallow capsules, or refractory nausea and vomiting, malabsorption, an external biliary shunt, or significant bowel resection that would preclude adequate absorption Congestive heart failure (CHF) New York (NY) Heart Association class III or IV; unstable coronary artery disease [myocardial infarction (MI) more than 6 months prior to study entry is permitted] or serious cardiac arrhythmia Baseline QT interval corrected using Fridericia equation (QTcF) ≥ 450 msec (for males) or ≥ 470 msec (for females) at Screening Active or chronic infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) Known chronic liver disease Women who are breast-feeding or pregnant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Leader
Organizational Affiliation
Daiichi Sankyo, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Facility Name
Sun Yat-sen Hospital
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
Samsung Medical Center
City
Seoul
State/Province
Gangnam-Gu
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
State/Province
Seodaemun-gu
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma

We'll reach out to this number within 24 hrs