Trial Outcomes & Findings for Phase II Trial of Dasatinib in Patients With Isocitrate Dehydrogenase (IDH)-Mutant Advanced Intrahepatic Cholangiocarcinoma (NCT NCT02428855)

NCT ID: NCT02428855

Last Updated: 2020-07-31

Results Overview

The number of participants that achieved either a complete or partial response, as assessed by Response Criteria in Solid Tumors (RECIST 1.1) * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 8 participants
• Primary outcome timeframe: 8 Weeks
• Results posted on: 2020-07-31

Participant Flow

Participant milestones

Measure	Dasatinib Patients with advanced intrahepatic cholangiocarcinoma who have either IDH1 or IDH2 mutations and have received at least one prior platinum containing regimen * Dasatinib, oral, daily, predetermined dosage per cycle * Radiologic Response Assessment every 2 cycles Dasatinib
Overall Study STARTED	8
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Dasatinib Patients with advanced intrahepatic cholangiocarcinoma who have either IDH1 or IDH2 mutations and have received at least one prior platinum containing regimen * Dasatinib, oral, daily, predetermined dosage per cycle * Radiologic Response Assessment every 2 cycles Dasatinib
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Dasatinib n=8 Participants Patients with advanced intrahepatic cholangiocarcinoma who have either IDH1 or IDH2 mutations and have received at least one prior platinum containing regimen * Dasatinib, oral, daily, predetermined dosage per cycle * Radiologic Response Assessment every 2 cycles Dasatinib
Age, Continuous	59 years n=8 Participants
Sex: Female, Male Female	6 Participants n=8 Participants
Sex: Female, Male Male	2 Participants n=8 Participants
Region of Enrollment United States	8 participants n=8 Participants
Tumor location Intrahepatic	7 Participants n=8 Participants
Tumor location Hilar	1 Participants n=8 Participants
IDH Mutation IDH1	7 Participants n=8 Participants
IDH Mutation IDH2	1 Participants n=8 Participants

PRIMARY outcome

Timeframe: 8 Weeks

The number of participants that achieved either a complete or partial response, as assessed by Response Criteria in Solid Tumors (RECIST 1.1)

• Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
• Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	Dasatinib n=8 Participants Patients with advanced intrahepatic cholangiocarcinoma who have either IDH1 or IDH2 mutations and have received at least one prior platinum containing regimen * Dasatinib, oral, daily, predetermined dosage per cycle * Radiologic Response Assessment every 2 cycles Dasatinib
Objective Response Rate (ORR) Complete Response (CR)	0 Participants
Objective Response Rate (ORR) Partial Response (CR)	0 Participants

SECONDARY outcome

Timeframe: From registration until disease progression or death, median duration of 8.7 weeks

The median amount of time from registration until disease progression or death, whichever occurs first. Disease progression was assessed via RECIST 1.1 criteria:

> Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Outcome measures

Measure	Dasatinib n=8 Participants Patients with advanced intrahepatic cholangiocarcinoma who have either IDH1 or IDH2 mutations and have received at least one prior platinum containing regimen * Dasatinib, oral, daily, predetermined dosage per cycle * Radiologic Response Assessment every 2 cycles Dasatinib
Median Progression Free Survival (PFS)	8.7 Weeks Interval 6.4 to Upper limit of the confidence interval is not defined due to an insufficient number of events occurring.

SECONDARY outcome

Timeframe: From the time of registration until death, median duration of 37.9 weeks

The median amount of time from registration until death. Participants are censored at the date last known alive.

Outcome measures

Measure	Dasatinib n=8 Participants Patients with advanced intrahepatic cholangiocarcinoma who have either IDH1 or IDH2 mutations and have received at least one prior platinum containing regimen * Dasatinib, oral, daily, predetermined dosage per cycle * Radiologic Response Assessment every 2 cycles Dasatinib
Overall Survival	37.9 Weeks Interval 20.7 to The upper limit of the confidence interval is not defined due to an insufficient number of events occurring.

SECONDARY outcome

Timeframe: From the start of treatment until 30 days after the end of treatment, median duration of 3 months

The number of participants that experienced an adverse event as assessed by Common Toxicology Criteria for Adverse Events (CTCAE 4.0)

Outcome measures

Measure	Dasatinib n=8 Participants Patients with advanced intrahepatic cholangiocarcinoma who have either IDH1 or IDH2 mutations and have received at least one prior platinum containing regimen * Dasatinib, oral, daily, predetermined dosage per cycle * Radiologic Response Assessment every 2 cycles Dasatinib
Number of Participants With Adverse Events	8 Participants

Adverse Events

Dasatinib

Serious events: 8 serious events

Other events: 0 other events

Deaths: 7 deaths

Serious adverse events

Measure	Dasatinib n=8 participants at risk Patients with advanced intrahepatic cholangiocarcinoma who have either IDH1 or IDH2 mutations and have received at least one prior platinum containing regimen * Dasatinib, oral, daily, predetermined dosage per cycle * Radiologic Response Assessment every 2 cycles
Blood and lymphatic system disorders Lymphopenia	50.0% 4/8 • From the start of treatment until 30 days after the end of treatment, median duration of 3 months Only grade 3 or greater treatment related adverse events were recorded
Blood and lymphatic system disorders Anemia	12.5% 1/8 • From the start of treatment until 30 days after the end of treatment, median duration of 3 months Only grade 3 or greater treatment related adverse events were recorded
Metabolism and nutrition disorders Hyponatremia	12.5% 1/8 • From the start of treatment until 30 days after the end of treatment, median duration of 3 months Only grade 3 or greater treatment related adverse events were recorded
Metabolism and nutrition disorders Hypophosphatemia	12.5% 1/8 • From the start of treatment until 30 days after the end of treatment, median duration of 3 months Only grade 3 or greater treatment related adverse events were recorded
Investigations Aspartate aminotransferase increased	12.5% 1/8 • From the start of treatment until 30 days after the end of treatment, median duration of 3 months Only grade 3 or greater treatment related adverse events were recorded
Reproductive system and breast disorders Menorrhagia	12.5% 1/8 • From the start of treatment until 30 days after the end of treatment, median duration of 3 months Only grade 3 or greater treatment related adverse events were recorded

Other adverse events

Adverse event data not reported

Additional Information

Dr. Bruce Giantonio

Massachusetts General Hospital

Phone: 617-724-4000

Email: BGIANTONIO@mgh.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place