Clinical trial NCT02975700: 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
Overall status: COMPLETED
Phase: NA
Conditions: Melanoma
Keywords: PLX3397
Kit-mutant Melanoma
Unresectable or Metastatic KIT-mutated Melanoma
Developmental Phase I/II
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2016-11-29
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Summary of Best Overall Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
timeFrame: within 18 months postdose
measure: Objective Response Rate (ORR) Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
timeFrame: within 18 months postdose
Secondary outcomes:
measure: Duration of Response Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
timeFrame: within 18 months postdose
measure: Progression-free Survival Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
timeFrame: within 18 months postdose
measure: Overall Survival Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
timeFrame: within 18 months postdose
measure: Disease Control Rate Following Twice Daily Administration of PL3397 at 1000 mg/Day In Participants With Unresectable or Advanced KIT-mutated Melanoma
timeFrame: within 18 months postdose
measure: 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
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose
measure: 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
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose
measure: 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
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose
measure: 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
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose
measure: 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
timeFrame: Cycle 1, Day 1 and Day 15 at predose, 0.5 h, 1h, 2h, 4h, and 6h postdose
measure: 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
timeFrame: within 28 days after administration of the last dose of study drug, up to 18 months postdose
measure: 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
timeFrame: within 28 days after administration of the last dose of study drug, up to 18 months postdose
measure: 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
timeFrame: within 28 days after administration of the last dose of study drug, up to 18 months postdose
measure: 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
timeFrame: within 28 days after administration of the last dose of study drug, up to 18 months postdose
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen Hospital
state: Guangdong
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-Gu
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seodaemun-gu
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: