Trial Outcomes & Findings for Multicenter Study Of CPX-1 (Irinotecan HCl: Floxuridine) Liposome Injection In Patients With Advanced Colorectal Cancer (NCT NCT00361842)
NCT ID: NCT00361842
Last Updated: 2021-07-02
Results Overview
Disease response was assessed using RECIST 1.0. Measurable disease and target lesions were determined prior to study entry. Changes in the largest diameter (unidimensional measurement) of the sum of the target tumor lesions were used in the RECIST criteria. Best response on study was classified as follows. Complete Response (CR), disappearance of all clinical and radiological evidence of tumor. Partial Response (PR) at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum of the longest diameters. Stable Disease (SD), steady state of disease. Neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD. Progressive Disease (PD) at least a 20% increase in the sum of the longest diameters of measured lesions taking as references the smallest sum of longest diameters recorded since the treatment started. Appearance of new lesions also constituted progressive disease.
COMPLETED
PHASE2
65 participants
From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
2021-07-02
Participant Flow
Participant milestones
| Measure |
Irinotecan - Naïve
|
Irinotecan - Exposed
|
|---|---|---|
|
Overall Study
STARTED
|
28
|
35
|
|
Overall Study
COMPLETED
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
27
|
34
|
Reasons for withdrawal
| Measure |
Irinotecan - Naïve
|
Irinotecan - Exposed
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
|
Overall Study
Death
|
2
|
1
|
|
Overall Study
Disease progression
|
19
|
20
|
|
Overall Study
Adverse Event
|
2
|
3
|
|
Overall Study
Occurrence of unacceptable toxicity
|
1
|
5
|
|
Overall Study
Other
|
0
|
2
|
Baseline Characteristics
Multicenter Study Of CPX-1 (Irinotecan HCl: Floxuridine) Liposome Injection In Patients With Advanced Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Irinotecan - Naïve
n=26 Participants
|
Irinotecan - Exposed
n=33 Participants
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.9 years
STANDARD_DEVIATION 9.62 • n=5 Participants
|
60.2 years
STANDARD_DEVIATION 10.92 • n=7 Participants
|
60.1 years
STANDARD_DEVIATION 10.28 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
8 participants
n=5 Participants
|
17 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
16 participants
n=7 Participants
|
34 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 monthsPopulation: The response rate efficacy evaluable (RECIST) analysis set (n=21 in group 1 and n= 24 in group 2) included all enrolled participants who received at least 1 cycle of CPX-1 therapy (2 doses, Days 1 and 15) and had at least 1 measurable lesion assessed for response (either after every second cycle of treatment or earlier to document disease progression) after beginning treatment. Tumor response, based on the RECIST criteria, was assessed at baseline and every 8 weeks.
Disease response was assessed using RECIST 1.0. Measurable disease and target lesions were determined prior to study entry. Changes in the largest diameter (unidimensional measurement) of the sum of the target tumor lesions were used in the RECIST criteria. Best response on study was classified as follows. Complete Response (CR), disappearance of all clinical and radiological evidence of tumor. Partial Response (PR) at least a 30% decrease in the sum of the longest diameter of target lesions taking as reference the baseline sum of the longest diameters. Stable Disease (SD), steady state of disease. Neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD. Progressive Disease (PD) at least a 20% increase in the sum of the longest diameters of measured lesions taking as references the smallest sum of longest diameters recorded since the treatment started. Appearance of new lesions also constituted progressive disease.
Outcome measures
| Measure |
Irinotecan - Naïve
n=21 Participants
* No prior exposure to irinotecan
* No more than 1 regimen for metastatic disease
* No more than 2 regimens overall;
* 1 for neoadjuvant/adjuvant and 1 for metastatic/advanced disease
|
Irinotecan - Exposed
n=24 Participants
* Prior exposure to irinotecan was required
* Disease progression on or within 6 months after completion of prior irinotecan-containing regimen
* CPX-1 treatment must start within 12 months after documentation of disease progression on irinotecan (other therapies are permitted after irinotecan and before study entry)
|
|---|---|---|
|
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0
Complete Response (CR)
|
0 Participants
|
0 Participants
|
|
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0
Partial Response (PR)
|
2 Participants
|
0 Participants
|
|
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0
Stable Disease (SD)
|
11 Participants
|
12 Participants
|
|
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0
Progressive Disease (PD)
|
8 Participants
|
11 Participants
|
PRIMARY outcome
Timeframe: Every 8 weeksPopulation: The efficacy evaluable analysis set or "Full Analysis Set" (25 patients in Group 1 and 32 participants in Group 2) included all enrolled participants who received at least 1 dose of CPX-1 therapy, and had at least one post-baseline PFS assessment.
Progression-free survival (PFS) was defined as the time from the first dose to the documentation of progressive disease (PD), death, or lost to follow-up at last assessment visit.
Outcome measures
| Measure |
Irinotecan - Naïve
n=25 Participants
* No prior exposure to irinotecan
* No more than 1 regimen for metastatic disease
* No more than 2 regimens overall;
* 1 for neoadjuvant/adjuvant and 1 for metastatic/advanced disease
|
Irinotecan - Exposed
n=32 Participants
* Prior exposure to irinotecan was required
* Disease progression on or within 6 months after completion of prior irinotecan-containing regimen
* CPX-1 treatment must start within 12 months after documentation of disease progression on irinotecan (other therapies are permitted after irinotecan and before study entry)
|
|---|---|---|
|
Progression-free Survival (PFS) Per RECIST Version 1.0
|
4.69 months
Standard Error 0.84
|
3.48 months
Standard Error 0.44
|
SECONDARY outcome
Timeframe: Every 8 weeksPopulation: No participants had CR. Two participants in the naïve group had objective responses. One participant showed a PR on study day 57 that lasted for 5.8 months. One participant had a PR starting on study day 60 and persisting for 9.1 months at which time the data was censored. Due to the censored observation, the median DoR was not estimable (NE).
The duration of overall response was measured from the time that measurement criteria were met for CR or PR (whichever status was recorded first) until the first date that recurrent or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall complete response was measured from the time measurement criteria were first met for complete response until the first date that recurrent disease was objectively documented.
Outcome measures
| Measure |
Irinotecan - Naïve
n=2 Participants
* No prior exposure to irinotecan
* No more than 1 regimen for metastatic disease
* No more than 2 regimens overall;
* 1 for neoadjuvant/adjuvant and 1 for metastatic/advanced disease
|
Irinotecan - Exposed
* Prior exposure to irinotecan was required
* Disease progression on or within 6 months after completion of prior irinotecan-containing regimen
* CPX-1 treatment must start within 12 months after documentation of disease progression on irinotecan (other therapies are permitted after irinotecan and before study entry)
|
|---|---|---|
|
Duration of Response (DoR) Per RECIST Version 1.0
|
NA months
Interval 5.8 to 9.1
One participant had a PR starting on study day 60 and persisting for 9.1 months at which time the data was censored. Due to the censored observation, the median DoR was not estimable (NE).
|
—
|
Adverse Events
Irinotecan - Naïve
Irinotecan - Exposed
Serious adverse events
| Measure |
Irinotecan - Naïve
n=26 participants at risk
|
Irinotecan - Exposed
n=33 participants at risk
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
15.4%
4/26
|
3.0%
1/33
|
|
Blood and lymphatic system disorders
Neutropenia
|
11.5%
3/26
|
3.0%
1/33
|
|
Gastrointestinal disorders
Pyrexia
|
7.7%
2/26
|
3.0%
1/33
|
|
Infections and infestations
Pneumonia
|
7.7%
2/26
|
3.0%
1/33
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
0.00%
0/26
|
6.1%
2/33
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
2/26
|
0.00%
0/33
|
|
Metabolism and nutrition disorders
Dehydration
|
7.7%
2/26
|
0.00%
0/33
|
|
Cardiac disorders
Cardio-respiratory Arrest
|
3.8%
1/26
|
0.00%
0/33
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/26
|
3.0%
1/33
|
|
Gastrointestinal disorders
Enteritis
|
3.8%
1/26
|
0.00%
0/33
|
|
Gastrointestinal disorders
GI Hemorrhage
|
3.8%
1/26
|
0.00%
0/33
|
|
Gastrointestinal disorders
Nausea
|
3.8%
1/26
|
0.00%
0/33
|
|
Gastrointestinal disorders
Small Intestine Obstruction
|
0.00%
0/26
|
3.0%
1/33
|
|
General disorders
General Physical Deterioration
|
3.8%
1/26
|
0.00%
0/33
|
|
Gastrointestinal disorders
Infusion Related Reaction
|
0.00%
0/26
|
3.0%
1/33
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/26
|
3.0%
1/33
|
|
Infections and infestations
Sepsis
|
0.00%
0/26
|
3.0%
1/33
|
|
Infections and infestations
Staphylococcal Sepsis
|
3.8%
1/26
|
0.00%
0/33
|
|
Injury, poisoning and procedural complications
Accidental Overdose
|
0.00%
0/26
|
3.0%
1/33
|
|
Injury, poisoning and procedural complications
GI Stoma Complication
|
3.8%
1/26
|
0.00%
0/33
|
|
Investigations
Neutrophil Count Decreased
|
0.00%
0/26
|
3.0%
1/33
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis to Lung
|
0.00%
0/26
|
3.0%
1/33
|
|
Psychiatric disorders
Anxiety
|
3.8%
1/26
|
0.00%
0/33
|
|
Respiratory, thoracic and mediastinal disorders
Orthopnea
|
0.00%
0/26
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration
|
0.00%
0/26
|
3.0%
1/33
|
|
Vascular disorders
Peripheral Arterial Occlusive Disease
|
3.8%
1/26
|
0.00%
0/33
|
|
General disorders
Disease Progression
|
0.00%
0/26
|
6.1%
2/33
|
Other adverse events
| Measure |
Irinotecan - Naïve
n=26 participants at risk
|
Irinotecan - Exposed
n=33 participants at risk
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
19.2%
5/26
|
15.2%
5/33
|
|
Blood and lymphatic system disorders
Neutropenia
|
19.2%
5/26
|
42.4%
14/33
|
|
Gastrointestinal disorders
Abdominal Pain
|
38.5%
10/26
|
18.2%
6/33
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
7.7%
2/26
|
9.1%
3/33
|
|
Gastrointestinal disorders
Constipation
|
26.9%
7/26
|
24.2%
8/33
|
|
Gastrointestinal disorders
Diarrhea
|
84.6%
22/26
|
78.8%
26/33
|
|
Gastrointestinal disorders
Dry Mouth
|
3.8%
1/26
|
6.1%
2/33
|
|
Gastrointestinal disorders
Dyspepsia
|
15.4%
4/26
|
15.2%
5/33
|
|
Gastrointestinal disorders
Flatulence
|
23.1%
6/26
|
12.1%
4/33
|
|
Gastrointestinal disorders
Nausea
|
80.8%
21/26
|
72.7%
24/33
|
|
Gastrointestinal disorders
Vomiting
|
69.2%
18/26
|
51.5%
17/33
|
|
General disorders
Asthenia
|
23.1%
6/26
|
9.1%
3/33
|
|
General disorders
Chills
|
15.4%
4/26
|
9.1%
3/33
|
|
General disorders
Fatigue
|
57.7%
15/26
|
66.7%
22/33
|
|
General disorders
Mucosal Inflammation
|
7.7%
2/26
|
9.1%
3/33
|
|
General disorders
Edema, Peripheral
|
3.8%
1/26
|
6.1%
2/33
|
|
General disorders
Pyrexia
|
15.4%
4/26
|
24.2%
8/33
|
|
Infections and infestations
Nasopharyngitis
|
7.7%
2/26
|
3.0%
1/33
|
|
Infections and infestations
Urinary Tract Infection
|
11.5%
3/26
|
9.1%
3/33
|
|
Investigations
Neutrophil Count Decreased
|
0.00%
0/26
|
9.1%
3/33
|
|
Investigations
Weight Decreased
|
23.1%
6/26
|
33.3%
11/33
|
|
Metabolism and nutrition disorders
Anorexia
|
38.5%
10/26
|
39.4%
13/33
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
11.5%
3/26
|
12.1%
4/33
|
|
Metabolism and nutrition disorders
Dehydration
|
30.8%
8/26
|
18.2%
6/33
|
|
Metabolism and nutrition disorders
Hypokalemia
|
19.2%
5/26
|
12.1%
4/33
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
15.4%
4/26
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
15.4%
4/26
|
9.1%
3/33
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
3.8%
1/26
|
6.1%
2/33
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
11.5%
3/26
|
6.1%
2/33
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
3.8%
1/26
|
9.1%
3/33
|
|
Nervous system disorders
Dizziness
|
3.8%
1/26
|
6.1%
2/33
|
|
Nervous system disorders
Headache
|
19.2%
5/26
|
18.2%
6/33
|
|
Psychiatric disorders
Anxiety
|
3.8%
1/26
|
6.1%
2/33
|
|
Psychiatric disorders
Depression
|
11.5%
3/26
|
15.2%
5/33
|
|
Psychiatric disorders
Insomnia
|
7.7%
2/26
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.2%
5/26
|
3.0%
1/33
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea, Exertional
|
3.8%
1/26
|
6.1%
2/33
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
30.8%
8/26
|
27.3%
9/33
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/26
|
9.1%
3/33
|
|
Skin and subcutaneous tissue disorders
Night Sweats
|
7.7%
2/26
|
3.0%
1/33
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.8%
1/26
|
15.2%
5/33
|
|
Vascular disorders
Hot Flush
|
7.7%
2/26
|
3.0%
1/33
|
|
Vascular disorders
Hypotension
|
0.00%
0/26
|
12.1%
4/33
|
Additional Information
Director, Clinical Trial Disclosure & Transparency
Jazz Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review trial results communications prior to public release and can embargo such communications for a period of at least 60 days from the time submitted to sponsor for review. If requested by sponsor, the PI will withhold publication for up to an additional 30 days. Furthermore, the first publication of study results must be a joint publication of all study sites unless a joint manuscript has not been submitted for publication within 12 months of completion of the study.
- Publication restrictions are in place
Restriction type: OTHER