Cholangiocarcinoma
Conditions
Keywords
Phase II, Safety, Tolerability, Efficacy, Amphinex-induced Photochemical Internalisation, PCI, Amphinex, Gemcitabine, Cisplatin, Inoperable, CCA, Cholangiocarcinoma, Bile duct cancer, Photodynamic therapy, Extrahepatic, Perihilar, Distal, Fimaporfin, Pivotal, RELEASE, PDT, FimaChem, Klatskin, First line treatment, Standard of care, SOC, Chemotherapy, Local treatment
Brief summary
This study will assess the safety and effectiveness of fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy compared to gemcitabine/cisplatin alone, in patients with inoperable cholangiocarcinoma (CCA). Participants will be randomly assigned to one of the treatment groups and will receive study treatment for 6 months, followed by assessments every 3 months, as applicable.
Detailed description
Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma arising from cells lining the bile ducts. Standard treatment options for CCA include surgery, radiotherapy and chemotherapy, dependent upon if the CCA is intra- or extra-hepatic. Surgical removal of the tumor is the only potential cure, and CCA is very resistant to standard pharmaceutical drug treatment, though chemotherapy has some effect. Current chemotherapy uses cisplatin plus gemcitabine. Photochemical internalisation (PCI) is a novel technology, where photochemical reactions are used to enhance the effect of drugs by increasing their ability cross cell membranes to interact with their intended target. This study will assess the safety and effectiveness of fimaporfin-induced PCI of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy compared to gemcitabine/cisplatin alone, in patients with inoperable CCA. NOTE: Participants are no longer being recruited to this study.
Interventions
DRUGFimaporfin and Gemcitabine
PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given.
DRUGGemcitabine/Cisplatin chemotherapy
Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered.
Sponsors
PCI Biotech AS
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
1. Each patient must provide signed and witnessed written informed consent and agree to comply with study protocol requirements. 2. Histopathologically/cytologically verified adenocarcinoma consistent with cholangiocarcinoma (CCA). Must have biliary lesion causing bile obstruction that requires stenting and is accessible for PCI light treatment (ie, extrahepatic CCA \[perihilar or distal\] only). 3. CCA must be considered inoperable with respect to radical resection. 4. At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation. 5. If metastatic, metastases must be limited tissues other than bone or the central nervous system. 6. Must have adequate biliary drainage (at least 50% of the liver volume or at least 2 sectors) with no evidence of active uncontrolled infection (patients on antibiotics are eligible). 7. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. Estimated life expectancy of at least 12 weeks.
Exclusion criteria
1. Patients who have previously received any anti-tumor (either local or systemic) treatment for CCA, except for previous treatment of up to 2 cycles of gemcitabine/cisplatin. 2. Patients with severe visceral disease other than CCA. 3. A history of frequently recurring septic biliary events. 4. Patients with porphyria or hypersensitivity to porphyrins. 5. Patients with a second primary cancer with a disease-free interval of \<5 years. A second primary cancer that has been treated with intent to cure may be allowed after consultation with the study Medical Monitor. Adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, in-situ carcinoma of the uterine cervix, or prostate cancer that is controlled by hormone therapy (patients may continue hormone therapy while on study) are allowed. 6. Patients not able to undergo contrast-enhanced CT or MRI. 7. Patients currently participating in any other interventional clinical trial. 8. Planned surgery, endoscopic examination or dental treatment in the first 30 days after PCI treatment. 9. Co-existing ophthalmic disease likely to require slit-lamp examination within the first 90 days after PCI treatment. 10. Clinically significant and uncontrolled cardiac disease except for extra systoles or minor conduction abnormalities and controlled and well-treated chronic atrial fibrillation. 11. Known allergy or sensitivity to photosensitisers (active substance and/or any of the excipients); or chronic use of other photosensitising therapies; treatment with amiodarone during the last 12 months. 12. Known hypersensitivity to or contraindication to the use of gemcitabine (active substance and/or any of the excipients). 13. Known hypersensitivity to or contraindication to the use of cisplatin (active substance and/or any of the excipients). 14. Patients with ataxia telangiectasia. 15. Upon the Investigator's discretion, evidence of any other medical conditions (such as psychiatric illness, physical examination or laboratory findings) that may interfere with the planned PCI treatment, affect patient compliance or place the patient at high risk from treatment-related complications. 16. Patients planning to have or who have recently had vaccination with a live vaccine. 17. Patients concurrently receiving treatment with phenytoin. 18. Male patients unwilling to use highly effective contraception or female patients of childbearing potential unwilling to use highly effective form of contraception. Patients must continue the use of contraception during PCI treatment and subsequent chemotherapy for at least 6 months thereafter. 19. Women who are breastfeeding or who have a positive pregnancy test at baseline. 20. Patients with inadequate bone marrow function (absolute neutrophil count \<1.5 x 10\^9/L; platelet count \<100 x 10\^9/L; haemoglobin \<6 mmol/L \[transfusion allowed\]). 21. Inadequate liver function despite satisfactory drainage (serum bilirubin persisting at \>5 x upper limit of normal for the institution; aspartate aminotransferase or alanine aminotransferase \>3.0 x upper limit of normal or \>5 x upper limit of normal if liver metastases are present; alkaline phosphatase levels \>5.0 x upper limit of normal). 22. Inadequate renal function, as determined by local practice for patients on fractionated platinum-based chemotherapy. Patients with creatinine clearance \<45 mL/min (in France: \<60 mL/min) must not be included. Other protocol-defined criteria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to 18 months | From date of randomisation to date of objective disease progression or death, whichever comes first (in months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (BOR) | Up to 18 months | Best response recorded from start of treatment until disease progression/recurrence (according to RECIST 1.1) |
| Objective Response Rate (ORR) | Up to 18 months | Proportion of patients with measurable disease at baseline who have at least one visit response with a complete response (CR) or partial response (PR) noted (according to RECIST 1.1) |
| Duration of Response (DoR) | Up to 24 months | From first documented tumour response until first documented disease progression, or death in the absence of disease progression (in months) |
| Overall Disease Control Rate (DCR) | 6 months and 12 months | Proportion of patients with BOR of CR, PR or stable disease (SD) (according to RECIST 1.1) at or after the first follow-up scan, partial response or complete response |
| Change in Tumor Size | Up to 18 months | Best overall percentage change in tumour size from baseline |
| Overall Survival (OS) | Up to 24 months | From date of randomisation to date of death from any cause (in months) |
| Adverse Events (AEs)/Serious Adverse Events (SAEs) | Up to 12 months | Number and proportion of patients with AEs/SAEs |
| Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | Time Frame AUC calculated from time zero to C5-D8 (3 months from the first PCI treatment) | A non-compartmental analysis (NCA) was applied on the data. AUC from time zero to the last measured concentration (AUC 0-t) was initially estimated by the linear trapezoidal method. |
| Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | Timepoints for pharmacokinetic (PK) sampling: Day -4 (before, 30m and 4hrs after Amphinex), C1-D1, C1-D8, C2-D8, C3-D8, C4-D8, C4-D18 (before, 30m and 4hrs after Amphinex), C5-D1, and C5-D8 | A non-compartmental analysis (NCA) was applied on the data. |
| Time to Cmax (Tmax) Was Performed for Patients in Arm A. | Timepoints for PK sampling: Day -4 (before, 30 min and 4 hours after Amphinex), C1-D1, C1-D8, C2-D8, C3-D8, C4-D8, C4-D18 (before, 30 min and 4 hours after Amphinex) , C5-D1, and C5-D8 | A non-compartmental analysis (NCA) was applied on the data as described by Gabrielsson & Weiner (Methods in molecular biology, 929:161-180, 2012). |
| Health-related Quality of Life (QoL) | Up to 18 months | QoL assessment. Patients select one of four answers to 22 questions ranging from 1 (not at all) to 4 (very much). Lower total scores indicate a more favorable QoL perception than a higher score. |
| Loco-regional Tumour-related Events and Biliary Complications | Up to 12 months | Frequency and severity of loco-regional tumour related events and biliary complications |
Countries
Belgium, Denmark, Finland, France, Germany, Italy, Norway, Poland, South Korea, Spain, Sweden, Taiwan, Ukraine, United States
Participant flow
Pre-assignment details
Of the 41 enrolled participants, all met inclusion criteria and were randomized and included in the intent-to-great (ITT) analysis set.
Participants by arm
| Arm | Count |
|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) Arm A: Fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by gemcitabine/cisplatin chemotherapy. Length of cycle is 3 weeks with PCI treatment at Day 1.
Fimaporfin and Gemcitabine: PCI treatment consists of IV administration of Amphinex solution for injection (investigational product) at 0.22 mg/kg dose of fimaporfin, followed 4 days later by a standard dose of gemcitabine infusion (1000 mg/m²) and intraluminal laser light application. Up to 2 PCI treatments will be given.
Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered. | 21 |
| Standard of Care (SoC) Arm B: Gemcitabine/cisplatin chemotherapy. Length of cycle is 3 weeks.
Gemcitabine/Cisplatin chemotherapy: Up to 8 cycles of gemcitabine/cisplatin combination chemotherapy will be administered. | 20 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 5 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Study terminated by sponsor | 9 | 11 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | PCI Treatment in Conjunction With Standard of Care (SoC) | Standard of Care (SoC) | Total |
|---|---|---|---|
| Age, Continuous | 68.1 years STANDARD_DEVIATION 7.3 | 64.4 years STANDARD_DEVIATION 11.43 | 66.3 years STANDARD_DEVIATION 9.61 |
| Age, Customized 50 to <65 years of age | 6 Participants | 7 Participants | 13 Participants |
| Age, Customized <50 years of age | 0 Participants | 2 Participants | 2 Participants |
| Age, Customized >=65 years of age | 15 Participants | 11 Participants | 26 Participants |
| Race/Ethnicity, Customized African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants | 9 Participants | 19 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 20 Participants | 19 Participants | 39 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 18 Participants |
| Sex: Female, Male Male | 14 Participants | 9 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 19 | 2 / 15 |
| other Total, other adverse events | 18 / 18 | 16 / 16 |
| serious Total, serious adverse events | 12 / 18 | 8 / 16 |
Outcome results
Primary
Progression-free Survival (PFS)
From date of randomisation to date of objective disease progression or death, whichever comes first (in months)
Time frame: Up to 18 months
Population: Modified intent-to-treat (mITT) analysis set (all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Progression-free Survival (PFS) | 7.29 Months |
| Standard of Care (SoC) | Progression-free Survival (PFS) | 8.08 Months |
Secondary
Adverse Events (AEs)/Serious Adverse Events (SAEs)
Number and proportion of patients with AEs/SAEs
Time frame: Up to 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Adverse Events (AEs)/Serious Adverse Events (SAEs) | 12 Participants |
| Standard of Care (SoC) | Adverse Events (AEs)/Serious Adverse Events (SAEs) | 8 Participants |
Secondary
Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A.
A non-compartmental analysis (NCA) was applied on the data. AUC from time zero to the last measured concentration (AUC 0-t) was initially estimated by the linear trapezoidal method.
Time frame: Time Frame AUC calculated from time zero to C5-D8 (3 months from the first PCI treatment)
Population: AUC was calculated for each single patient and not for the population since the study was terminated and the amount of data was limited. No mean and standard deviation was calculated for the population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 106-01 2nd dose | 874614 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 101-01 1st dose | 1017672 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 101-01 2nd dose | 1399905 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 101-02 | 385730 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 101-03 1st dose | 576835 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 101-03 2nd dose | 600546 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 106-01 1st dose (No samples taken before 90 hrs, therefore AUC values is likely underestimated) | 677373 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 111-02 1st dose | 492274 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 111-02 2nd dose | NA (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 181-06 1st dose | 566460 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 181-06 2nd dose | NA (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 183-03 1st dose | 751771 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 183-03 2nd dose | 475001 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 183-03 3rd dose | 646845 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 187-02 1st dose | 709053 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 187-02 2nd dose | 383882 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 192-01 | 805049 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 303-01 1st dose | 434347 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 303-01 2nd dose | NA (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 303-02 1st dose | 681663 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 303-02 2nd dose | 730864 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 401-01 | 521326 (ng/ml)*hrs |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Area Under the Plasma Concentration Curve (AUC) Was Performed for Patients in Arm A. | 501-01 | 549955 (ng/ml)*hrs |
Secondary
Best Overall Response (BOR)
Best response recorded from start of treatment until disease progression/recurrence (according to RECIST 1.1)
Time frame: Up to 18 months
Population: Modified intent-to-treat (mITT) analysis set (all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Best Overall Response (BOR) | Progressive disease | 4 Participants |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Best Overall Response (BOR) | Partial response | 3 Participants |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Best Overall Response (BOR) | Stable disease | 12 Participants |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Best Overall Response (BOR) | Complete response | 0 Participants |
| Standard of Care (SoC) | Best Overall Response (BOR) | Progressive disease | 1 Participants |
| Standard of Care (SoC) | Best Overall Response (BOR) | Complete response | 0 Participants |
| Standard of Care (SoC) | Best Overall Response (BOR) | Partial response | 3 Participants |
| Standard of Care (SoC) | Best Overall Response (BOR) | Stable disease | 11 Participants |
Comparison: BOR is summarized by randomized treatment group using the mITT analysis set.
Secondary
Change in Tumor Size
Best overall percentage change in tumour size from baseline
Time frame: Up to 18 months
Population: Only patients with measurable disease at baseline are included in this summary.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Change in Tumor Size | -12.06 Percentage Change in Tumor Size | Standard Deviation 28.008 |
| Standard of Care (SoC) | Change in Tumor Size | -14.73 Percentage Change in Tumor Size | Standard Deviation 16.377 |
Comparison: Change in tumor size in percentage was summarized for the subset of patients in the mITT analysis set who had measurable disease at baseline.
Secondary
Duration of Response (DoR)
From first documented tumour response until first documented disease progression, or death in the absence of disease progression (in months)
Time frame: Up to 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Duration of Response (DoR) | Patient A | 169 Days |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Duration of Response (DoR) | Patient B | 260 Days |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Duration of Response (DoR) | Patient C | 264 Days |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Duration of Response (DoR) | Patient D | NA Days |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Duration of Response (DoR) | Patient E | NA Days |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Duration of Response (DoR) | Patient F | NA Days |
| Standard of Care (SoC) | Duration of Response (DoR) | Patient E | 1 Days |
| Standard of Care (SoC) | Duration of Response (DoR) | Patient A | NA Days |
| Standard of Care (SoC) | Duration of Response (DoR) | Patient D | 85 Days |
| Standard of Care (SoC) | Duration of Response (DoR) | Patient B | NA Days |
| Standard of Care (SoC) | Duration of Response (DoR) | Patient F | 1 Days |
| Standard of Care (SoC) | Duration of Response (DoR) | Patient C | NA Days |
Comparison: The DoR was calculated only for those with a documented response of CR or PR and is defined as the time from the date of first documented tumor response until the first date of documented disease progression or death, whichever is earlier.
Secondary
Health-related Quality of Life (QoL)
QoL assessment. Patients select one of four answers to 22 questions ranging from 1 (not at all) to 4 (very much). Lower total scores indicate a more favorable QoL perception than a higher score.
Time frame: Up to 18 months
Population: The RELEASE study did not collect QoL data.
Secondary
Loco-regional Tumour-related Events and Biliary Complications
Frequency and severity of loco-regional tumour related events and biliary complications
Time frame: Up to 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Loco-regional Tumour-related Events and Biliary Complications | 12 Participants |
| Standard of Care (SoC) | Loco-regional Tumour-related Events and Biliary Complications | 8 Participants |
Secondary
Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A.
A non-compartmental analysis (NCA) was applied on the data.
Time frame: Timepoints for pharmacokinetic (PK) sampling: Day -4 (before, 30m and 4hrs after Amphinex), C1-D1, C1-D8, C2-D8, C3-D8, C4-D8, C4-D18 (before, 30m and 4hrs after Amphinex), C5-D1, and C5-D8
Population: Maximum observed concentration (Cmax) was performed for patients in arm A.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 101-01 2nd dose | 2377 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 101-01 1st dose | 2462 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 101-02 | 2631 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 101-03 1st dose | 2495 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 101-03 2nd dose | 3172 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 106-01 1st dose (No samples taken before 90 hrs, Cmax value likely underestimated) | 800 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 106-01 2nd dose | 2923 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 111-02 1st dose | 2221 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 111-02 2nd dose | 3255 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 181-06 1st dose (No sample at 30 minutes, Cmax is likely underestimated) | 1427 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 181-06 2nd dose | 2321 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 183-03 1st dose | 2624 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 183-03 2nd dose | 2187 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 183-03 3rd dose | 2571 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 187-02 1st dose | 2750 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 187-02 2nd dose | 1937 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 192-01 | 2017 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 303-01 1st dose | 2606 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 303-01 2nd dose | 1848 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 303-02 1st dose | 2868 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 303-02 2nd dose | 3124 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 401-01 | 2912 ng/ml |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Maximum Observed Concentration (Cmax) Was Performed for Patients in Arm A. | 501-01 | 2300 ng/ml |
Secondary
Objective Response Rate (ORR)
Proportion of patients with measurable disease at baseline who have at least one visit response with a complete response (CR) or partial response (PR) noted (according to RECIST 1.1)
Time frame: Up to 18 months
Population: Modified intent-to-treat (mITT) analysis set (all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Objective Response Rate (ORR) | 3 Participants |
| Standard of Care (SoC) | Objective Response Rate (ORR) | 3 Participants |
Secondary
Overall Disease Control Rate (DCR)
Proportion of patients with BOR of CR, PR or stable disease (SD) (according to RECIST 1.1) at or after the first follow-up scan, partial response or complete response
Time frame: 6 months and 12 months
Population: Modified intent-to-treat (mITT) analysis set (all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Overall Disease Control Rate (DCR) | Overall Disease Control Rate | 15 Participants |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Overall Disease Control Rate (DCR) | Disease Control Rate at 6 Months | 11 Participants |
| Standard of Care (SoC) | Overall Disease Control Rate (DCR) | Overall Disease Control Rate | 14 Participants |
| Standard of Care (SoC) | Overall Disease Control Rate (DCR) | Disease Control Rate at 6 Months | 10 Participants |
Comparison: DCR is reported and includes any patient with a best response of stable disease, PR or CR.
Secondary
Overall Survival (OS)
From date of randomisation to date of death from any cause (in months)
Time frame: Up to 24 months
Population: Modified intent-to-treat (mITT) analysis set (all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Overall Survival (OS) | 12 Participants |
| Standard of Care (SoC) | Overall Survival (OS) | 13 Participants |
Comparison: OS was analyzed using the modified intent-to-treat (mITT) analysis set, which included all randomized participants who received at least 1 dose of study treatment and had a RECIST assessment at baseline. Kaplan Meier Curve (KM) analysis of OS was completed for the mITT population, but the number of events was too small to draw any conclusions.
Secondary
Time to Cmax (Tmax) Was Performed for Patients in Arm A.
A non-compartmental analysis (NCA) was applied on the data as described by Gabrielsson & Weiner (Methods in molecular biology, 929:161-180, 2012).
Time frame: Timepoints for PK sampling: Day -4 (before, 30 min and 4 hours after Amphinex), C1-D1, C1-D8, C2-D8, C3-D8, C4-D8, C4-D18 (before, 30 min and 4 hours after Amphinex) , C5-D1, and C5-D8
Population: A standard non-compartmental PK analysis (NCA) of bioanalytical data from 13 patients dosed with fimaporfin was performed for the RELEASE study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 183-03 2nd dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 101-01 1st dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 101-01 2nd dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 101-02 | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 101-03 1st dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 101-03 2nd dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 106-01 1st dose (No samples taken before 90 hrs, erroneous data) | 90 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 106-01 2nd dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 111-02 1st dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 111-02 2nd dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 181-06 1st dose (No sample at 30 minutes) | 4 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 181-06 2nd dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 183-03 1st dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 183-03 3rd dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 187-02 1st dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 187-02 2nd dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 192-01 | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 303-01 1st dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 303-01 2nd dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 303-02 1st dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 303-02 2nd dose | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 401-01 | 0.50 hours |
| PCI Treatment in Conjunction With Standard of Care (SoC) | Time to Cmax (Tmax) Was Performed for Patients in Arm A. | 501-01 | 0.50 hours |