Trial Outcomes & Findings for FOLFIRI Alone Versus FOLFIRI Plus Bevacizumab Versus FOLFIRI Plus E7820 as Second-Line Therapy in Patients With Locally Advanced or Metastatic Colorectal Cancer (NCT NCT01133990)
NCT ID: NCT01133990
Last Updated: 2023-11-07
Results Overview
Dose-limiting toxicities were defined as clinically significant adverse events (AEs) occurring less than or equal to (\<=) 28 days after commencing study treatment and considered by the investigator to be possibly or probably related to study treatment. Toxicity was evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v.4.0).
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
5 participants
Primary outcome timeframe
Cycle 1 (each cycle length=28 days)
Results posted on
2023-11-07
Participant Flow
Participants took part in the study at 4 investigative sites in Australia and the United States from 04 March 2010 to 18 February 2011.
A total of 5 participants were enrolled and treated in Phase 1b part of the study and only safety was analyzed for all participants in this study. The planned dose escalation of E7820 at 70 milligram per day (mg/day), 100 mg/day and Phase 2 part were not conducted as the study was terminated early without determination of the Maximum Tolerated Dose (MTD) as the combination of E7820 plus FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil \[5-FU\]) was deemed to be not tolerable.
Participant milestones
| Measure |
Phase 1b: E7820 40 mg/Day + FOLFIRI
Participants received E7820 40 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 milligram per square meter (mg/m\^2), Leucovorin 200 mg/m\^2 administered by intravenous (IV) infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-fluorouracil (5-FU) administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by continuous IV (CIV) infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants continued to receive study treatment unless there was occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: E7820 70 mg/Day + FOLFIRI
Participants were planned to receive E7820 70 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 1b: E7820 100 mg/Day + FOLFIRI
Participants were planned to receive E7820 100 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: FOLFIRI
Participants were planned to receive FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: FOLFIRI + Bevacizumab
Participants were planned to receive FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle followed by Bevacizumab 5 mg/kg, IV infusion on Days 1 and 15 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: E7820 (RP2D) + FOLFIRI
Participants were planned to receive E7820 70 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
|---|---|---|---|---|---|---|
|
Phase 1b (Dose Escalation Phase)
STARTED
|
5
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1b (Dose Escalation Phase)
COMPLETED
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1b (Dose Escalation Phase)
NOT COMPLETED
|
4
|
0
|
0
|
0
|
0
|
0
|
|
Phase 2 (Dose-confirmation Phase)
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Phase 2 (Dose-confirmation Phase)
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Phase 2 (Dose-confirmation Phase)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Phase 1b: E7820 40 mg/Day + FOLFIRI
Participants received E7820 40 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 milligram per square meter (mg/m\^2), Leucovorin 200 mg/m\^2 administered by intravenous (IV) infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-fluorouracil (5-FU) administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by continuous IV (CIV) infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants continued to receive study treatment unless there was occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: E7820 70 mg/Day + FOLFIRI
Participants were planned to receive E7820 70 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 1b: E7820 100 mg/Day + FOLFIRI
Participants were planned to receive E7820 100 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: FOLFIRI
Participants were planned to receive FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: FOLFIRI + Bevacizumab
Participants were planned to receive FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle followed by Bevacizumab 5 mg/kg, IV infusion on Days 1 and 15 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: E7820 (RP2D) + FOLFIRI
Participants were planned to receive E7820 70 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
|---|---|---|---|---|---|---|
|
Phase 1b (Dose Escalation Phase)
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1b (Dose Escalation Phase)
Physician Decision
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1b (Dose Escalation Phase)
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1b (Dose Escalation Phase)
Progression of disease
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
FOLFIRI Alone Versus FOLFIRI Plus Bevacizumab Versus FOLFIRI Plus E7820 as Second-Line Therapy in Patients With Locally Advanced or Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Phase 1b: E7820 40 mg/Day + FOLFIRI
n=5 Participants
Participants received E7820 40 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5 -FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants continued to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|
|
Age, Customized
43 - 83 years
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (each cycle length=28 days)Population: Safety population included all participants who received at least one dose of study drug and who had safety assessment post the first dose.
Dose-limiting toxicities were defined as clinically significant adverse events (AEs) occurring less than or equal to (\<=) 28 days after commencing study treatment and considered by the investigator to be possibly or probably related to study treatment. Toxicity was evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v.4.0).
Outcome measures
| Measure |
Phase 1b: E7820 40 mg/Day + FOLFIRI
n=5 Participants
Participants received E7820 40 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5 -FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants continued to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: FOLFIRI + Bevacizumab
Participants were planned to receive FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle followed by Bevacizumab 5 mg/kg, IV infusion on Days 1 and 15 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: E7820 (RP2D) + FOLFIRI
Participants were planned to receive E7820 70 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
|---|---|---|---|
|
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
|
2 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)Population: Safety population included all participants who received at least one dose of study drug and who had safety assessment post the first dose.
Adverse Events were defined as TEAEs if they started on or after the date and time of administration of the first dose of study drug during the study. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. Any change in hematology, clinical chemistry, urine values and regular measurement of vital signs which were deemed clinically significant by the investigator were recorded as TEAE.
Outcome measures
| Measure |
Phase 1b: E7820 40 mg/Day + FOLFIRI
n=5 Participants
Participants received E7820 40 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5 -FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants continued to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: FOLFIRI + Bevacizumab
Participants were planned to receive FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle followed by Bevacizumab 5 mg/kg, IV infusion on Days 1 and 15 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: E7820 (RP2D) + FOLFIRI
Participants were planned to receive E7820 70 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
|---|---|---|---|
|
Phase 1b: Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)
|
5 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)Population: Safety population included all participants who received at least one dose of study drug and who had safety assessment post the first dose.
ECOG-PS measured participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (greater than\[ \>\] 50 percent \[%\] of waking hours), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair \>50% of waking hours; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead.
Outcome measures
| Measure |
Phase 1b: E7820 40 mg/Day + FOLFIRI
n=5 Participants
Participants received E7820 40 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5 -FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants continued to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: FOLFIRI + Bevacizumab
Participants were planned to receive FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle followed by Bevacizumab 5 mg/kg, IV infusion on Days 1 and 15 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: E7820 (RP2D) + FOLFIRI
Participants were planned to receive E7820 70 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
|---|---|---|---|
|
Phase 1b: Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
Participants With ECOG-PS Grade 1
|
1 Participants
|
—
|
—
|
|
Phase 1b: Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
Participants With ECOG-PS Grade 2
|
2 Participants
|
—
|
—
|
|
Phase 1b: Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
Participants With ECOG-PS Grade 3
|
2 Participants
|
—
|
—
|
|
Phase 1b: Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
Participants With ECOG-PS Grade 4
|
0 Participants
|
—
|
—
|
|
Phase 1b: Number of Participants With Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
Participants With ECOG-PS Grade 5
|
0 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)Population: Safety population included all participants who received at least one dose of study drug and who had safety assessment post the first dose.
Physical examination included examination of the head, eyes, ears, nose, throat, neck, heart, chest, lungs, abdomen, extremities, skin, lymph nodes, and neurological status.
Outcome measures
| Measure |
Phase 1b: E7820 40 mg/Day + FOLFIRI
n=5 Participants
Participants received E7820 40 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5 -FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants continued to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: FOLFIRI + Bevacizumab
Participants were planned to receive FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle followed by Bevacizumab 5 mg/kg, IV infusion on Days 1 and 15 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: E7820 (RP2D) + FOLFIRI
Participants were planned to receive E7820 70 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
|---|---|---|---|
|
Phase 1b: Number of Participants With Clinically Significant Changes in Physical Examinations
|
2 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)Population: Safety population included all participants who received at least one dose of study drug and who had safety assessment post the first dose.
ECG was to be a complete standardized 12-lead recording. The ECGs were reviewed by the investigator or designee prior to study drug administration as part of the participant's standard of care.
Outcome measures
| Measure |
Phase 1b: E7820 40 mg/Day + FOLFIRI
n=5 Participants
Participants received E7820 40 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5 -FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants continued to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: FOLFIRI + Bevacizumab
Participants were planned to receive FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle followed by Bevacizumab 5 mg/kg, IV infusion on Days 1 and 15 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
Phase 2: E7820 (RP2D) + FOLFIRI
Participants were planned to receive E7820 70 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5-FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants were planned to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first. No participants were enrolled in this arm. The study did not progress beyond Phase 1b (E7820 40 mg/day).
|
|---|---|---|---|
|
Phase 1b: Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECGs) Parameter
|
1 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From the date of randomization to date of PD or death (whichever occurred first), up to 11 monthsPopulation: The study was terminated before the initiation of Phase 2, so the data for this outcome measure was not collected and analyzed.
PFS was defined as the time from the date of randomization of a participant to the date of first documentation of PD or death (whichever occurred first) based on investigator assessments according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. PD was defined as at least a 20% increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From date randomization to date of PD or death, up to 11 monthsPopulation: The study was terminated before the initiation of Phase 2, so the data for this outcome measure was not collected and analyzed.
TTP was defined as time from the date of randomization of a participant until the date of first documented progression of such participant's disease based on investigator assessments according to RECIST v.1.1. PD was defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From date of treatment start to until date of first PD or death (whichever occurred first), up to 11 monthsPopulation: The study was terminated before the initiation of Phase 2, so the data for this outcome measure was not collected and analyzed.
ORR was defined as percentage of participants in the study whose best overall response was either CR or PR based on investigator assessments according to RECIST v1.1. A confirmatory scan was required after no less than 4 weeks and no later than 8 weeks, starting on the date that the response was first recorded. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<)10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From date of randomization to date of PD or death, up to 11 monthsPopulation: The study was terminated before the initiation of Phase 2, so the data for this outcome measure was not collected and analyzed.
OS was defined as time from the date of randomization of a participant until the date of death of such participant, regardless of the actual cause of the participant's death.
Outcome measures
Outcome data not reported
Adverse Events
Phase 1b: E7820 40 mg/Day + FOLFIRI
Serious events: 2 serious events
Other events: 5 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Phase 1b: E7820 40 mg/Day + FOLFIRI
n=5 participants at risk
Participants received E7820 40 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5 -FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants continued to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|
|
Infections and infestations
Sepsis
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Infections and infestations
Septic shock
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
Other adverse events
| Measure |
Phase 1b: E7820 40 mg/Day + FOLFIRI
n=5 participants at risk
Participants received E7820 40 mg/day tablets orally, in combination with a FOLFIRI regimen on Days 1 to 2 and 15 to 16 of each 28-day treatment cycle. FOLFIRI regimen consisted of; Irinotecan 180 mg/m\^2, Leucovorin 200 mg/m\^2 administered by IV infusion on Days 1 and 15 of each 28-day treatment cycle, and 400 mg/m\^2 5 -FU administered as an IV bolus injection followed by a total of 2400 mg/m\^2 5-FU administered by CIV infusion over 46 hours on Days 1 to 2, then repeated on Days 15 to 16 of each 28-day treatment cycle. Participants continued to receive study treatment unless there was occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|
|
General disorders
Fatigue
|
60.0%
3/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
40.0%
2/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
General disorders
Mucosal inflammation
|
40.0%
2/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Blood and lymphatic system disorders
Neutropenia
|
40.0%
2/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Investigations
Weight decreased
|
40.0%
2/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Abdominal discomfort
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Cardiac disorders
Acute myocardial infarction
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
General disorders
Adverse drug reaction
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Nervous system disorders
Amnesia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Ascites
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Skin and subcutaneous tissue disorders
Blister
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
General disorders
Chest pain
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Constipation
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Metabolism and nutrition disorders
Dehydration
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Nervous system disorders
Dizziness
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Nervous system disorders
Dysgeusia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Dyspepsia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Renal and urinary disorders
Dysuria
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Gastritis
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Haematochezia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Blood and lymphatic system disorders
Leukopenia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Mouth ulceration
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Nausea
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
General disorders
Oedema
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
General disorders
Oedema peripheral
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Oesophagitis
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Infections and infestations
Oral candidiasis
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Vascular disorders
Orthostatic hypotension
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Cardiac disorders
Palpitations
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
General disorders
Pyrexia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Stomatitis
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Nervous system disorders
Syncope
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Vascular disorders
Venous occlusion
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
|
Infections and infestations
Vulvovaginal candidiasis
|
20.0%
1/5 • Phase 1b: From date of first dose up to 30 days after last dose of study treatment (up to 11.5 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER