Trial Outcomes & Findings for ISIS 183750 With Irinotecan for Advanced Solid Tumors or Colorectal Cancer (NCT NCT01675128)
NCT ID: NCT01675128
Last Updated: 2016-04-25
Results Overview
MTD is the dose level at which no more than 1 of up to 6 patients experience dose-limiting toxicity (DLT) during the first 6 weeks of treatment, and no dose below that which at least 2 (of \</=6) patients have DLT as a result of the drug.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
24 participants
Primary outcome timeframe
2 years
Results posted on
2016-04-25
Participant Flow
Participant milestones
| Measure |
Phase I Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 started 800 mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Overall Study
STARTED
|
4
|
10
|
10
|
|
Overall Study
COMPLETED
|
2
|
8
|
9
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
1
|
Reasons for withdrawal
| Measure |
Phase I Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 started 800 mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Overall Study
Disease progression on study
|
1
|
1
|
1
|
|
Overall Study
Refused further treatment
|
1
|
0
|
0
|
|
Overall Study
Pulmonary complication; off study
|
0
|
1
|
0
|
Baseline Characteristics
ISIS 183750 With Irinotecan for Advanced Solid Tumors or Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Phase I Dose Level I
n=4 Participants
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
n=10 Participants
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
n=10 Participants
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Age, Continuous
|
61.6 years
n=5 Participants
|
65.7 years
n=7 Participants
|
60.6 years
n=5 Participants
|
62.7 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
10 participants
n=7 Participants
|
10 participants
n=5 Participants
|
24 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 2 yearsMTD is the dose level at which no more than 1 of up to 6 patients experience dose-limiting toxicity (DLT) during the first 6 weeks of treatment, and no dose below that which at least 2 (of \</=6) patients have DLT as a result of the drug.
Outcome measures
| Measure |
All Phase I Participants
n=14 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Maximum Tolerated Dose (MTD) of ISIS 183750 in Advanced Solid Tumors
|
1000 mg
|
—
|
—
|
PRIMARY outcome
Timeframe: 2 yearsMTD is the dose level at which no more than 1 of up to 6 patients experience dose-limiting toxicity (DLT) during the first 6 weeks of treatment, and no dose below that which at least 2 (of \</=6) patients have DLT as a result of the drug.
Outcome measures
| Measure |
All Phase I Participants
n=14 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Maximum Tolerated Dose of Irinotecan in Advanced Solid Tumors
|
160 mg/m^2
|
—
|
—
|
PRIMARY outcome
Timeframe: 2 weeksPopulation: Mandatory pre- and post-dose biopsies for elF4e messenger ribonucleic acid (mRNA) analysis was performed in the phase II portion of the study.
A change in elF4e levels is defined as an increase or decrease compared to baseline and is measured between two time points before rand after 2 weeks of treatment by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).
Outcome measures
| Measure |
All Phase I Participants
n=9 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Number of Participants With a Change in the Level of a Particular Gene Called elF4E [Eukaryotic Initiation Factors (elF)4e Messenger Ribonucleic Acid (mRNA) Levels] in Matched Pre and Post Tumor Biopsies
|
5 participants
|
—
|
—
|
PRIMARY outcome
Timeframe: 2 weeksPopulation: Mandatory pre- and post-dose biopsies for elF4e messenger ribonucleic acid (mRNA) analysis was performed in the phase II portion of the study.
A change in protein is defined as an increase or decrease compared to baseline and is measured between two time points by immunohistochemistry (IHC) analysis.
Outcome measures
| Measure |
All Phase I Participants
n=9 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Number of Participants With a Change in elF4e Protein Levels in Matched Pre and Post Tumor Biopsies
|
5 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 21 monthsHere is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Outcome measures
| Measure |
All Phase I Participants
n=4 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
n=10 Participants
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
n=10 Participants
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Number of Participants With Adverse Events
|
4 participants
|
10 participants
|
10 participants
|
SECONDARY outcome
Timeframe: up to 2 cyclesPopulation: Only 6/10 participants in Phase I, Dose Level II and 9/10 participants in Phase II were evaluable for response. Per protocol, no responses were to be reported for the Phase I Dose Level I Arm because the participants have different histologies, thus there are no objective responses for Phase I Dose Level I.
Objective response was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in short axis to \<10mm. Partial response (PR) is at least a 30% reduction in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is at least a 20% increase in the sum of athe 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 lesions is also considered progression).
Outcome measures
| Measure |
All Phase I Participants
n=6 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
n=9 Participants
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Objective Response
Partial Response (PR)
|
0 participants
|
0 participants
|
—
|
|
Objective Response
Stable Disease (SD)
|
3 participants
|
4 participants
|
—
|
|
Objective Response
Progressive (PD)
|
3 participants
|
5 participants
|
—
|
|
Objective Response
Complete Response (CR)
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: ≤ 6 monthsPopulation: Only 6/10 participants in Phase I, Dose Level II and 9/10 participants in Phase II were evaluable. Per protocol, progression free survival was not to be reported for the Phase I Dose Level I Arm because the participants have different histologies, thus there is no progression free survival data for Phase I Dose Level I.
Progression free survival is defined as the time beginning on the on study date and continuing until date of progression or date removed from study for an adverse event.
Outcome measures
| Measure |
All Phase I Participants
n=6 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
n=9 Participants
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Number of Participants With Progression Free Survival
|
3 participants
|
6 participants
|
—
|
SECONDARY outcome
Timeframe: ≥ 12 monthsPopulation: Only 6/10 participants in Phase I, Dose Level II and 9/10 participants in Phase II were evaluable. Per protocol, overall survival was not to be reported for the Phase I Dose Level I Arm because the participants have different histologies, thus overall survival data for Phase I Dose Level I.
Overall survival is defined as the time from the on study date until the date of death or date last known alive.
Outcome measures
| Measure |
All Phase I Participants
n=6 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
n=9 Participants
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Overall Survival
|
1 participants
|
1 participants
|
—
|
SECONDARY outcome
Timeframe: up to 24 hours post end of infusionPopulation: Phase I Dose Level I and Phase I Dose Level II were grouped together for this outcome measure. Complete pharmacokinetic data for only ten of the fourteen participants enrolled on the phase I portion of the study were available for analysis. Data is unavailable to report each individual time point.
AUC(ALL) (Area under the plasma concentration vs. time curve for all time points) was assessed for CPT-11 (irinotecan), its active metabolite SN38, and the glucuronic acid metabolite of SN38, SN38-G to derive the total AUC(ALL).
Outcome measures
| Measure |
All Phase I Participants
n=10 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
AUC(ALL) (Area Under the Plasma Concentration vs. Time Curve for All Time Points)
CPT-11 (irinotecan)
|
9016 hr*ng/mL
Standard Deviation 1793
|
—
|
—
|
|
AUC(ALL) (Area Under the Plasma Concentration vs. Time Curve for All Time Points)
SN38
|
119 hr*ng/mL
Standard Deviation 42.3
|
—
|
—
|
|
AUC(ALL) (Area Under the Plasma Concentration vs. Time Curve for All Time Points)
SN38-G
|
1340 hr*ng/mL
Standard Deviation 751
|
—
|
—
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: Per protocol, this outcome measure was assessed in the phase II portion only because all participants were getting the same dose.
Intracellular and stromal presence of ISIS in tumor tissue was assessed by immunohistochemistry (IHC) and Crystal Violet staining to determine effectiveness of drug. Tissue that retains stain indicates intracellular and stromal presence of ISIS and determines if the drug is working. Relative staining intensity (intensity criteria unavailable) was evaluated by a pathologist.
Outcome measures
| Measure |
All Phase I Participants
n=10 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Number of Participants With Intracellular and Stromal Presence of ISIS in Tumor Tissue
|
10 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: Per protocol, this outcome measure was assessed in the phase II portion only because all participants were getting the same dose.
Protein levels in the biopsy sample was assessed by immunohistochemistry using anti-oligonucleotide antibody to assess the downstream effect and determine if proteins are being manufactured. The number of participants with a reduced effect (criteria unavailable) of elF4E inhibition on relevant regulated proteins determines if the drug is working.
Outcome measures
| Measure |
All Phase I Participants
n=10 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Number of Participants With a Reduced Effect of elF4E Inhibition on Relevant Regulated Proteins
|
10 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: Per protocol, this outcome measure was assessed in the phase II portion only because all participants were getting the same dose.
Peripheral blood analysis of elF4E mRNA expression was performed using real time quantitative polymerase chain reaction (q-PCR) to assess the downstream effect and determine if proteins are being manufactured. The number of participants with a decrease (criteria unavailable) in elF4E determines if the drug is working. Cell proliferation or reduction was evaluated by a pathologist.
Outcome measures
| Measure |
All Phase I Participants
n=10 Participants
ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Number of Participants With a Decrease in elF4E mRNA Expression in Peripheral Blood
|
10 participants
|
—
|
—
|
Adverse Events
Phase I Dose Level I
Serious events: 3 serious events
Other events: 4 other events
Deaths: 0 deaths
Phase I Dose Level II
Serious events: 3 serious events
Other events: 10 other events
Deaths: 0 deaths
Phase II Dose Level I
Serious events: 4 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I Dose Level I
n=4 participants at risk
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
n=10 participants at risk
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
n=10 participants at risk
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Psychiatric disorders
Confusion
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Creatinine increased
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Death Not otherwise specified (NOS)
|
50.0%
2/4 • Number of events 2
|
0.00%
0/10
|
0.00%
0/10
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/4
|
0.00%
0/10
|
20.0%
2/10 • Number of events 2
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Fatigue
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Vascular disorders
Hematoma
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Endocrine disorders
Hyperthyroidism
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Vascular disorders
Hypotension
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Lipase increased
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Infections and infestations
Lung infection
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Gastrointestinal disorders
Pancreatitis
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Investigations
Serum amylase increased
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Vascular disorders
Thromboembolic event
|
25.0%
1/4 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Infections and infestations
Upper respiratory infection
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
Other adverse events
| Measure |
Phase I Dose Level I
n=4 participants at risk
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 started 800mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase I Dose Level II
n=10 participants at risk
Irinotecan 180 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered intravenously on Cycle 1 Days 1, 3, 5, 8, 15 and 22 of a 28 day cycle, restaged every 8 weeks.
|
Phase II Dose Level I
n=10 participants at risk
Irinotecan 160 mg/m\^2 every other week; ISIS 183750 1000mg/every week will be administered as an intravenous infusion every week without break, i.e. Days 1, 8, 15 and 22 of a 28-day cycle. Patients will be re-staged every 8 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Activated partial thromboplastin time prolonged
|
100.0%
4/4 • Number of events 7
|
70.0%
7/10 • Number of events 23
|
70.0%
7/10 • Number of events 14
|
|
Psychiatric disorders
Agitation
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
50.0%
2/4 • Number of events 2
|
60.0%
6/10 • Number of events 19
|
80.0%
8/10 • Number of events 31
|
|
Investigations
Alkaline phosphatase increased
|
50.0%
2/4 • Number of events 3
|
60.0%
6/10 • Number of events 14
|
90.0%
9/10 • Number of events 24
|
|
Immune system disorders
Allergic reaction
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
50.0%
2/4 • Number of events 2
|
20.0%
2/10 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
|
Blood and lymphatic system disorders
Anemia
|
100.0%
4/4 • Number of events 13
|
80.0%
8/10 • Number of events 28
|
90.0%
9/10 • Number of events 26
|
|
Metabolism and nutrition disorders
Anorexia
|
50.0%
2/4 • Number of events 2
|
50.0%
5/10 • Number of events 8
|
50.0%
5/10 • Number of events 7
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
50.0%
2/4 • Number of events 3
|
60.0%
6/10 • Number of events 10
|
70.0%
7/10 • Number of events 18
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
50.0%
2/4 • Number of events 2
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
30.0%
3/10 • Number of events 4
|
|
Eye disorders
Blurred vision
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Chills
|
0.00%
0/4
|
20.0%
2/10 • Number of events 2
|
20.0%
2/10 • Number of events 3
|
|
Psychiatric disorders
Confusion
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4
|
30.0%
3/10 • Number of events 3
|
50.0%
5/10 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Investigations
Creatinine increased
|
25.0%
1/4 • Number of events 2
|
30.0%
3/10 • Number of events 21
|
40.0%
4/10 • Number of events 9
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/4
|
30.0%
3/10 • Number of events 3
|
40.0%
4/10 • Number of events 6
|
|
Psychiatric disorders
Depression
|
25.0%
1/4 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Gastrointestinal disorders
Diarrhea
|
75.0%
3/4 • Number of events 6
|
60.0%
6/10 • Number of events 14
|
90.0%
9/10 • Number of events 17
|
|
Nervous system disorders
Dizziness
|
25.0%
1/4 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Nervous system disorders
Dysgeusia
|
25.0%
1/4 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/4
|
0.00%
0/10
|
20.0%
2/10 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
25.0%
1/4 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
General disorders
Edema limbs
|
25.0%
1/4 • Number of events 1
|
30.0%
3/10 • Number of events 4
|
30.0%
3/10 • Number of events 5
|
|
General disorders
Edema trunk
|
0.00%
0/4
|
0.00%
0/10
|
20.0%
2/10 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Eye disorders
Eye pain
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Fatigue
|
75.0%
3/4 • Number of events 5
|
40.0%
4/10 • Number of events 7
|
70.0%
7/10 • Number of events 10
|
|
General disorders
Fever
|
0.00%
0/4
|
60.0%
6/10 • Number of events 8
|
70.0%
7/10 • Number of events 12
|
|
General disorders
Flu like symptoms
|
0.00%
0/4
|
20.0%
2/10 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
|
Vascular disorders
Flushing
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
25.0%
1/4 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Headache
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
60.0%
6/10 • Number of events 6
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/4
|
20.0%
2/10 • Number of events 5
|
30.0%
3/10 • Number of events 8
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
0.00%
0/4
|
10.0%
1/10 • Number of events 2
|
10.0%
1/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypernatremia
|
0.00%
0/4
|
10.0%
1/10 • Number of events 2
|
10.0%
1/10 • Number of events 2
|
|
Nervous system disorders
Hypersomnia
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/4
|
20.0%
2/10 • Number of events 4
|
20.0%
2/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
100.0%
4/4 • Number of events 10
|
90.0%
9/10 • Number of events 36
|
90.0%
9/10 • Number of events 35
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
50.0%
2/4 • Number of events 2
|
10.0%
1/10 • Number of events 3
|
20.0%
2/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Metabolism and nutrition disorders
Hypokalemia
|
50.0%
2/4 • Number of events 8
|
50.0%
5/10 • Number of events 11
|
30.0%
3/10 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
25.0%
1/4 • Number of events 2
|
10.0%
1/10 • Number of events 4
|
20.0%
2/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatremia
|
50.0%
2/4 • Number of events 4
|
40.0%
4/10 • Number of events 5
|
90.0%
9/10 • Number of events 20
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
50.0%
2/4 • Number of events 3
|
60.0%
6/10 • Number of events 11
|
60.0%
6/10 • Number of events 14
|
|
Vascular disorders
Hypotension
|
25.0%
1/4 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
20.0%
2/10 • Number of events 2
|
|
General disorders
Infusion related reaction
|
0.00%
0/4
|
10.0%
1/10 • Number of events 2
|
10.0%
1/10 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
20.0%
2/10 • Number of events 2
|
|
Investigations
Lymphocyte count decreased
|
100.0%
4/4 • Number of events 22
|
60.0%
6/10 • Number of events 27
|
0.00%
0/10
|
|
General disorders
Malaise
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Skin and subcutaneous tissue disorders
Nail ridging
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
50.0%
2/4 • Number of events 2
|
60.0%
6/10 • Number of events 11
|
60.0%
6/10 • Number of events 10
|
|
Investigations
Neutrophil count decreased
|
75.0%
3/4 • Number of events 9
|
60.0%
6/10 • Number of events 35
|
40.0%
4/10 • Number of events 7
|
|
Gastrointestinal disorders
Obstruction gastric
|
25.0%
1/4 • Number of events 1
|
0.00%
0/10
|
0.00%
0/10
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Pain
|
25.0%
1/4 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
60.0%
6/10 • Number of events 10
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Platelet count decreased
|
75.0%
3/4 • Number of events 5
|
70.0%
7/10 • Number of events 25
|
60.0%
6/10 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Presyncope
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/4
|
20.0%
2/10 • Number of events 2
|
20.0%
2/10 • Number of events 2
|
|
Investigations
Serum amylase increased
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 2
|
|
Infections and infestations
Sinusitis
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
75.0%
3/4 • Number of events 4
|
40.0%
4/10 • Number of events 5
|
40.0%
4/10 • Number of events 4
|
|
Investigations
Weight loss
|
50.0%
2/4 • Number of events 2
|
30.0%
3/10 • Number of events 3
|
20.0%
2/10 • Number of events 2
|
|
Investigations
White blood cell decreased
|
100.0%
4/4 • Number of events 18
|
80.0%
8/10 • Number of events 51
|
70.0%
7/10 • Number of events 17
|
|
Injury, poisoning and procedural complications
Wound complication
|
0.00%
0/4
|
0.00%
0/10
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Edema face
|
0.00%
0/4
|
20.0%
2/10 • Number of events 3
|
0.00%
0/10
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
0.00%
0/10
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Vascular disorders
Hypertension
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Non-cardiac chest pain
|
0.00%
0/4
|
10.0%
1/10 • Number of events 2
|
10.0%
1/10 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Papulopustular rash
|
0.00%
0/4
|
20.0%
2/10 • Number of events 2
|
20.0%
2/10 • Number of events 2
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.00%
0/4
|
10.0%
1/10 • Number of events 2
|
10.0%
1/10 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/4
|
30.0%
3/10 • Number of events 3
|
30.0%
3/10 • Number of events 3
|
|
Gastrointestinal disorders
Rectal pain
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Stomach pain
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Reproductive system and breast disorders
Vaginal discharge
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Nervous system disorders- Other, specify (alteration in smell)
|
0.00%
0/4
|
10.0%
1/10 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4
|
10.0%
1/10 • Number of events 2
|
10.0%
1/10 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place