Liver Metastases, Colorectal Neoplasms, Neoplasm Metastasis, Neoplasm Recurrence, Local
Conditions
Keywords
Liver neoplasms, Liver metastases, MCRC, Litx™, LS11, Colorectal cancer with recurrent liver metastases
Brief summary
The purpose of the study is to assess the overall survival and progression free survival of patients treated with Litx™ + chemotherapy versus chemotherapy alone in the treatment of Colorectal Cancer with recurrent liver metastases, and to demonstrate the safety of Litx™ therapy. Litx™ consists of a light-activated drug, talaporfin sodium (LS11, Light Sciences Oncology, Bellevue, Washington), and a light generating device, composed of light-emitting diodes (LEDs), that is energized by a power controller and percutaneously placed in the target tumor tissue inside the body.
Detailed description
Randomized, stratified, two arm study: * Litx™ and chemotherapy arm (FOLFOX4 or FOLFIRI) * Chemotherapy only arm (FOLFOX4 or FOLFIRI) For patients who have progressed on FOLFIRI, they will be treated with Litx™ plus FOLFOX4 versus FOLFOX4 alone; and for patients who have progressed on FOLFOX, they will be treated with Litx™ plus FOLFIRI versus FOLFIRI alone. Stratification upon enrollment by chemotherapy and tumor sum of the longest diameter (SLD) (SLD \< 4 cm or SLD ≥4 cm but ≤7.5 cm).
Interventions
LS11 (Talaporfin Sodium) dose is 1mg/kg administered intravenously slow push (3-5 minutes).
PROCEDUREPercutaneous placement of device in liver metastases
Light Source placement will be conducted under placement imaging using ultrasound or CT guidance. No more than four Light Sources will be used at a single treatment session. The Light Sources may be used in a single lesion or in multiple lesions.
200 J/cm per Light Source at 20 mW/cm light energy
DRUGFOLFOX4 regimen
Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin
DRUGFOLFIRI regimen
Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan
Sponsors
Light Sciences Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with recurrent metastatic liver lesions from colorectal cancer who progressed on either FOLFOX or FOLFIRI * Biopsy proven evidence of colorectal cancer * At least one liver lesion that can be measured in one dimension at \>10 mm with spiral CT scan (CT preferred but MRI allowed) * ECOG Performance Status 0-2 * Life expectancy of at least 16 weeks * At least 30 days must have elapsed since the completion of any prior antineoplastic therapy and the patient must have recovered from acute side effects before day 0 * Understanding and ability to sign written informed consent * 18 years of age or more * Adequate hematologic, liver and renal functions as evidenced by the following: WBC \> 2.5 × 10\^9/L ; Platelet Count \> 100 × 10\^9/L ; Hemoglobin \> 90 g/L ; Neutrophils \>1.5 × 10\^9/L ; PT and PTT \< 1.5 Control ; SGOT, SGPT \< 5 × ULN ; GGT \< 5 × ULN ; Alkaline phosphatase \< 5 × ULN ; Bilirubin \< 3 × ULN ; Creatinine \< 1.5 × ULN
Exclusion criteria
* Patients who are candidates for complete surgical resection * Patients who received bevacizumab (Avastin®) or cetuximab (Erbitux®) within 30 days of randomization. Use of bevacizumab or cetuximab is prohibited while participating in this study * Patients who would require more than a total number of 12 light source applications over three Litx™ experimental treatments (no more than 4 light sources per treatment). * Patients who have a single measurable tumor greater than 7.5 cm in any organ * Target lesions irradiated within 3 months of randomization * Patients with tumor involvement in greater than 50% of parenchyma of the liver * Evidence of major vessel invasion of any organ * Patients with any non-colorectal cancers except for adequately treated basal or squamous cell skin cancer, or adequately treated stage I or II cancer from which the patient has been disease-free for ≥ 3 years, or other cancer from which the patient has been disease-free for ≥ 5 years * Known sensitivity to porphyrin-type drugs or known history of porphyria * Pregnancy or breast-feeding patients. A negative pregnancy test (urine or serum) from women of childbearing age is required prior to enrollment. A fertile patient must use effective contraception during participation in the study * Concurrent participation in another clinical trial involving experimental treatment * Any concurrent disease or condition that in the opinion of the investigator impairs the patient's ability to complete the trial such as psychological, familial, sociological, geographical or medical conditions which in the Principal Investigator's opinion could compromise compliance with the objectives and procedures of this protocol or obscure interpretation of the trial's data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 184 weeks | Time from randomization to death |
Countries
Austria, Bosnia and Herzegovina, Croatia, Germany, India, Italy, Latvia, Poland, Romania, Russia, Serbia, Sweden, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Litx + Chemotherapy Talaporfin sodium: LS11 (Talaporfin Sodium) dose is 1mg/kg administered intravenously slow push (3-5 minutes).
Percutaneous placement of device in liver metastases: Light Source placement will be conducted under placement imaging using ultrasound or CT guidance. No more than four Light Sources will be used at a single treatment session. The Light Sources may be used in a single lesion or in multiple lesions.
Interstitial light emitting diodes: 200 J/cm per Light Source at 20 mW/cm light energy
FOLFOX4 regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin
FOLFIRI regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan | 244 |
| Chemotherapy Alone FOLFOX4 regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and oxaliplatin
FOLFIRI regimen: Standard care chemotherapy regimen consisting of leucovorin, 5-FU and irinotecan | 239 |
| Total | 483 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 5 |
| Overall Study | No Reply at EOS | 7 | 7 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Status Unknown | 1 | 3 |
| Overall Study | Withdrawal by Subject | 15 | 14 |
Baseline characteristics
| Characteristic | Litx + Chemotherapy | Chemotherapy Alone | Total |
|---|---|---|---|
| Age, Continuous | 59.2 years STANDARD_DEVIATION 9.8 | 60.1 years STANDARD_DEVIATION 10.2 | 59.7 years STANDARD_DEVIATION 10 |
| Age, Customized | 60.0 years | 61.0 years | 60.0 years |
| Sex: Female, Male Female | 107 Participants | 97 Participants | 204 Participants |
| Sex: Female, Male Male | 137 Participants | 142 Participants | 279 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 201 / 222 | 207 / 232 |
| serious Total, serious adverse events | 66 / 222 | 52 / 232 |
Outcome results
Primary
Overall Survival
Time from randomization to death
Time frame: Up to 184 weeks
Population: ITT (All patient randomized/enrolled)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Litx + Chemotherapy | Overall Survival | 390 Days |
| Chemotherapy Alone | Overall Survival | 405 Days |