Intrahepatic Cholangiocarcinoma
Conditions
Brief summary
The study planned to evaluate the benefit of applying Selective Internal Radiation Therapy (SIRT) using SIR-Spheres Y-90 resin microspheres prior to receiving systemic chemotherapy treatment (cisplatin-gemcitabine, or CIS-GEM) in patients with unresectable intrahepatic cholangiocarcinoma. Half of the patients were randomized to CIS-GEM chemotherapy plus SIRT, and half of the patients were randomized to CIS-GEM alone.
Detailed description
This clinical study was a prospective, multicenter, randomized, controlled study evaluating SIR-Spheres Y-90 resin microspheres followed by cisplatin-gemcitabine (CIS-GEM) chemotherapy vs. CIS-GEM chemotherapy alone as first-line treatment of patients with unresectable intrahepatic cholangiocarcinoma. Randomized patients were to be followed until death, withdrawal of consent, or until end of study.
Interventions
DRUGCisplatin-gemcitabine
Systemic chemotherapy
DEVICERadiation: SIRT + chemotherapy (cisplatin-gemcitabine)
SIR-Spheres microspheres followed by systemic chemotherapy
Sponsors
Sirtex Medical
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
* Willing, able and mentally competent to provide written informed consent. * Aged 18 years or older. * Histologically or cytologically confirmed unresectable and non-ablatable intrahepatic cholangiocarcinoma. * Liver-only or liver predominant intrahepatic cholangiocarcinoma. Patient are permitted to have loco-regional lymph node involvement defined as: portal LN \</= to 2 cm and/or para aortic LN \</= to 1.5 cm in longest diameter, and/or up to 2 indeterminate lung lesions \< 1 cm if these lung lesions are positron emission tomography (PET) negative. * Chemotherapy naïve. Adjuvant chemotherapy is not permitted. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * Adequate hematological function defined as: Hemoglobin \>/= 10g/dL White Blood Cell count (WBC) \>/= 3.0 x 10\^9/L Absolute neutrophil count (ANC) \>/= 1.5 x 10\^9/L Platelet count \>/= 100,000/mm\^3 - Adequate liver function defined as: Total bilirubin \</= 30 umol/L (1.75 mg/dL) Albumin \>/= 30 g/L \- Adequate renal function defined as: Serum urea and serum creatinine \< 1.5 times upper limit of normal (ULN) Creatinine clearance \>/= 45 ml/min (calculated with Cockcroft-Gault Equation) * Life expectancy of at least 3 months without any active treatment * Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active use an acceptable method of contraception during the study. * Male patients must be surgically sterile or if sexually active must use an acceptable method of contraception during the study. * Considered suitable to receive either regimen in the clinical judgement of the treating investigator.
Exclusion criteria
* Patients with only non-measurable lesions in the liver according to RECIST criteria * Incomplete recovery from previous liver surgery, e.g. unresolved biliary tree obstruction or biliary sepsis or inadequate liver function * Biliary stent in situ * Main trunk Portal Vein Thrombosis (PVT) * Ascites, even if controlled with diuretics. (A minor peri-hepatic rim of ascites detected at imaging is acceptable). * Mixed hepatocellular carcinoma - intrahepatic cholangiocarcinoma (HCC-ICC) disease * History of prior malignancy. Exceptions include in-situ carcinoma of the cervix treated by cone-biopsy/resection, non-metastatic basal and/or squamous cell carcinomas of the skin, recurrent intra-hepatic cholangiocarcinoma post local treatment or any early stage (stage 1) malignancy adequately resected with curative intent at least 5 years prior to study entry * Suspicion of any bone metastasis/metastases or central nervous system metastasis/metastases on clinical or imaging examination. * Prior internal or external radiation delivered to the liver. * Pregnancy; breast feeding. * Participation within 28 days prior to randomization, in an active part of another clinical study that would compromise any of the endpoints of the study. * Evidence of ongoing active infection that may affect treatment feasibility or outcome. * Prior Whipple's procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival at 18 Months | 18 months following the date of randomization. | Survival at 18 months is defined as the proportion of patients still alive 18 months from the date of randomization. The outcome was analyzed but the clinical database is not deemed to be reliable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) at Any Site | From date of randomization to the date of progression at any site until the first date of documented tumor progression at any site or date of death from any cause, assessed up to 36 months. | PFS was defined as the time interval between randomization and the date of tumor progression. Diagnosis of tumor progression was to be made using RECIST 1.1. The outcome was not analyzed due to unreliability of the clinical database. |
| Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | From the date of first treatment until the date of date of first documented progression in the liver, assessed up to 36 months. | The outcome was not analyzed due to unreliability of the clinical database. |
| Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | From the date of first treatment until progression at any site, assessed up to 36 months. | The outcome was not analyzed due to unreliability of the clinical database. |
| Liver-specific Progression Free Survival (PFS) | From date of randomization to the first documented date of progression in the liver or date of death from any cause, assessed up to 36 months.. | Liver-specific PFS was defined as the number of days between randomization and the date of first tumor progression in the liver. Diagnosis of tumor progression was to be made using RECIST 1.1. |
| Liver Surgical Resection and Ablation Rate | 18 months following the date of randomization. | To assess the number of patients in each arm who are downstaged by protocol therapy and can proceed to liver resection or ablation. The specific assessments will be the classification of resection as R0, R1 or R2, the presence of viable tumor or fibrosis, and the nearest resection margin. The outcome was not analyzed due to unreliability of the clinical database. |
| Incidence of Adverse Events (Safety and Tolerability) | Informed consent until 28 days post last dose of protocol chemotherapy. | Adverse events (AEs) as assessed by CTCAE v. 4.0. Summaries of non-serious AEs (clinical database, MedDRA 20.1) and serious adverse events (SAEs; pharmacovigilance database, MedDRA 25.1) are provided for information only in the 'Adverse Events' section - the data are deemed unreliable. |
| Overall Survival | From date of randomization until the date of death from any cause, assessed up to 36 months. | The outcome was not analyzed due to unreliability of the clinical database. |
Countries
Australia, Belgium, France, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy (Cisplatin-Gemcitabine) Cisplatin 25mg/m2 in 1000ml 0.9% saline given over 1 hour followed by 500 ml 0.9% saline over 30 minutes, followed by Gemcitabine 1000 mg/m2 in 250-500 ml 0.9% saline over 30 minutes by intravenous infusions on days 1, and 8 of a 21-day cycle.
Cisplatin-gemcitabine: Systemic chemotherapy | 48 |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) A single treatment of hepatic arterial injection of SIR-Spheres Y-90 resin microspheres (SIRT) followed 14-16 days later by systemic chemotherapy (ABC-02 CIS-GEM protocol) with an intention to treat with 8 cycles of cisplatin + gemcitabine, or until progression, toxicity or patient choice. Treatment may be continued beyond 8 cycles in the absence of significant disease progression, at the treating clinicians' discretion.
Cisplatin-gemcitabine: Systemic chemotherapy
Radiation: SIRT + chemotherapy (cisplatin-gemcitabine): SIR-Spheres microspheres followed by systemic chemotherapy | 41 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Biopsy of tumor removed from resection | 1 | 0 |
| Overall Study | Death | 28 | 24 |
| Overall Study | In Study | 3 | 3 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Post Progression | 3 | 2 |
| Overall Study | Subject decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Chemotherapy (Cisplatin-Gemcitabine) | Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 24 Participants | 27 Participants | 51 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 14 Participants | 38 Participants |
| Age, Continuous | 61.94 years | 67.17 years | 64.35 years |
| Cirrhosis Absent | 41 Participants | 37 Participants | 78 Participants |
| Cirrhosis Present | 7 Participants | 4 Participants | 11 Participants |
| ECOG Performance Scale 0 | 33 Participants | 33 Participants | 66 Participants |
| ECOG Performance Scale 1 | 15 Participants | 8 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 10 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 30 Participants | 30 Participants | 60 Participants |
| Extent of liver involvement Non-whole | 32 Participants | 30 Participants | 62 Participants |
| Extent of liver involvement Whole | 16 Participants | 11 Participants | 27 Participants |
| Extra-hepatic disease Absent | 28 Participants | 21 Participants | 49 Participants |
| Extra-hepatic disease Present | 20 Participants | 20 Participants | 40 Participants |
| Prior Treatment No | 13 Participants | 15 Participants | 28 Participants |
| Prior Treatment Yes | 35 Participants | 26 Participants | 61 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 32 Participants | 31 Participants | 63 Participants |
| Race (NIH/OMB) White | 15 Participants | 9 Participants | 24 Participants |
| Region of Enrollment Australia | 1 participants | 2 participants | 3 participants |
| Region of Enrollment Belgium | 4 participants | 0 participants | 4 participants |
| Region of Enrollment France | 30 participants | 30 participants | 60 participants |
| Region of Enrollment Italy | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Netherlands | 2 participants | 3 participants | 5 participants |
| Region of Enrollment Spain | 4 participants | 2 participants | 6 participants |
| Region of Enrollment United Kingdom | 5 participants | 4 participants | 9 participants |
| Region of Enrollment United States | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 22 Participants | 23 Participants | 45 Participants |
| Sex: Female, Male Male | 26 Participants | 18 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 28 / 48 | 24 / 41 |
| other Total, other adverse events | 47 / 48 | 41 / 41 |
| serious Total, serious adverse events | 17 / 48 | 21 / 41 |
Outcome results
Primary
Survival at 18 Months
Survival at 18 months is defined as the proportion of patients still alive 18 months from the date of randomization. The outcome was analyzed but the clinical database is not deemed to be reliable.
Time frame: 18 months following the date of randomization.
Population: Randomized Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemotherapy (Cisplatin-Gemcitabine) | Survival at 18 Months | Yes | 25 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Survival at 18 Months | No | 23 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Survival at 18 Months | Yes | 23 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Survival at 18 Months | No | 18 Participants |
Secondary
Incidence of Adverse Events (Safety and Tolerability)
Adverse events (AEs) as assessed by CTCAE v. 4.0. Summaries of non-serious AEs (clinical database, MedDRA 20.1) and serious adverse events (SAEs; pharmacovigilance database, MedDRA 25.1) are provided for information only in the 'Adverse Events' section - the data are deemed unreliable.
Time frame: Informed consent until 28 days post last dose of protocol chemotherapy.
Population: The following endpoints reflects safety and tolerability data related to Adverse Event grade by category. Counts of participants with Grade 3 or higher adverse event severity by AE category by treatment arm are shown below.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Injury, poisoning and procedural complications | 0 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Gastrointestinal disorders | 5 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Investigations | 16 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Skin and subcutaneous tissue disorders | 0 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Metabolism and nutrition disorders | 3 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher General disorders and administration site conditions | 5 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Musculoskeletal and connective tissue disorders | 0 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Blood and lymphatic system disorders | 15 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Nervous system disorders | 0 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Hepatobiliary disorders | 3 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Psychiatric disorders | 0 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Respiratory, thoracic and mediastinal disorders | 4 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Renal and urinary disorders | 2 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Immune system disorders | 0 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Reproductive system and breast disorders | 1 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Cardiac disorders | 2 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Surgical and medical procedures | 0 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Infections and infestations | 3 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Vascular disorders | 4 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Serious Adverse Events | 17 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Vascular disorders | 4 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Skin and subcutaneous tissue disorders | 1 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Serious Adverse Events | 20 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Blood and lymphatic system disorders | 16 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Cardiac disorders | 2 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Gastrointestinal disorders | 5 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher General disorders and administration site conditions | 8 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Hepatobiliary disorders | 4 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Immune system disorders | 1 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Infections and infestations | 0 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Injury, poisoning and procedural complications | 1 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Investigations | 26 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Metabolism and nutrition disorders | 4 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Musculoskeletal and connective tissue disorders | 1 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Nervous system disorders | 3 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Psychiatric disorders | 1 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Renal and urinary disorders | 0 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Surgical and medical procedures | 2 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Incidence of Adverse Events (Safety and Tolerability) | Grade 3 or higher Reproductive system and breast disorders | 0 Participants |
Secondary
Liver-specific Progression Free Survival (PFS)
Liver-specific PFS was defined as the number of days between randomization and the date of first tumor progression in the liver. Diagnosis of tumor progression was to be made using RECIST 1.1.
Time frame: From date of randomization to the first documented date of progression in the liver or date of death from any cause, assessed up to 36 months..
Population: The data set we received for analysis showed only 17 CIS-GEM participants and 16 SIRT+CIS GEM participants with reported liver tumor progression data available. Due to database issues, the validity and reliability of this data is not complete.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chemotherapy (Cisplatin-Gemcitabine) | Liver-specific Progression Free Survival (PFS) | 323 Days to first tumor progression |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Liver-specific Progression Free Survival (PFS) | 369 Days to first tumor progression |
Secondary
Liver Surgical Resection and Ablation Rate
To assess the number of patients in each arm who are downstaged by protocol therapy and can proceed to liver resection or ablation. The specific assessments will be the classification of resection as R0, R1 or R2, the presence of viable tumor or fibrosis, and the nearest resection margin. The outcome was not analyzed due to unreliability of the clinical database.
Time frame: 18 months following the date of randomization.
Population: Data were collected for only 14 unique patients within the study due to early study termination and database issues. Any available data are reflected in the table. The validity and reliability of these data are not complete.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemotherapy (Cisplatin-Gemcitabine) | Liver Surgical Resection and Ablation Rate | Count of participants with resection only | 4 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Liver Surgical Resection and Ablation Rate | Count of participants with resection and ablation | 1 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Liver Surgical Resection and Ablation Rate | Count of participants with no resection or ablation | 2 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Liver Surgical Resection and Ablation Rate | Count of participants with resection only | 4 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Liver Surgical Resection and Ablation Rate | Count of participants with resection and ablation | 1 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Liver Surgical Resection and Ablation Rate | Count of participants with no resection or ablation | 2 Participants |
Secondary
Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site
The outcome was not analyzed due to unreliability of the clinical database.
Time frame: From the date of first treatment until progression at any site, assessed up to 36 months.
Population: The data we received showed 85 of our 89 subjects with any RECIST data present. These data were not available nor complete for each visit due to early study termination and database issues. Any available data is reflected in the table. The validity and reliability of these data are not complete.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Complete Response (CR) : RECIST 1.1 | 22 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Complete Response (CR) : Refined RECIST | 22 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Partial Response (PR) : RECIST 1.1 | 28 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Partial Response (PR) : Refined RECIST | 27 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Progressive Disease (PD) : RECIST 1.1 | 42 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Progressive Disease (PD) : Refined RECIST | 38 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Stable Disease (SD) : RECIST 1.1 | 103 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Stable Disease (SD) : Refined RECIST | 98 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Not Evaluable : RECIST 1.1 | 1 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Not Evaluable : Refined RECIST | 0 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Incomplete Form : RECIST 1.1 | 2 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Incomplete Form : Refined RECIST | 13 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Incomplete Form : RECIST 1.1 | 9 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Complete Response (CR) : RECIST 1.1 | 8 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Stable Disease (SD) : RECIST 1.1 | 102 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Complete Response (CR) : Refined RECIST | 7 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Not Evaluable : Refined RECIST | 7 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Partial Response (PR) : RECIST 1.1 | 28 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Stable Disease (SD) : Refined RECIST | 96 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Partial Response (PR) : Refined RECIST | 48 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Incomplete Form : Refined RECIST | 16 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Progressive Disease (PD) : RECIST 1.1 | 42 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Not Evaluable : RECIST 1.1 | 7 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site | Progressive Disease (PD) : Refined RECIST | 34 Number of Responses (RECIST 1.1+RRECIST) |
Secondary
Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver
The outcome was not analyzed due to unreliability of the clinical database.
Time frame: From the date of first treatment until the date of date of first documented progression in the liver, assessed up to 36 months.
Population: The data we received showed 85 of our 89 subjects with any RECIST data present. These data were not available nor complete for each visit due to early study termination and database issues. Any available data is reflected in the table. The validity and reliability of these data are not complete.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Complete Response (CR) : RECIST 1.1 | 22 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Complete Response (CR) : Refined RECIST | 21 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Partial Response (PR) : RECIST 1.1 | 25 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Partial Response (PR) : Refined RECIST | 24 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Progressive Disease (PD) : RECIST 1.1 | 23 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Progressive Disease (PD) : Refined RECIST | 22 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Stable Disease (SD) : RECIST 1.1 | 113 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Stable Disease (SD) : Refined RECIST | 105 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Not Evaluable : RECIST 1.1 | 13 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Not Evaluable : Refined RECIST | 13 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Incomplete Form : RECIST 1.1 | 2 Number of Responses (RECIST 1.1+RRECIST) |
| Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Incomplete Form : Refined RECIST | 13 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Incomplete Form : RECIST 1.1 | 9 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Complete Response (CR) : RECIST 1.1 | 10 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Stable Disease (SD) : RECIST 1.1 | 110 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Complete Response (CR) : Refined RECIST | 10 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Not Evaluable : Refined RECIST | 8 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Partial Response (PR) : RECIST 1.1 | 58 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Stable Disease (SD) : Refined RECIST | 105 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Partial Response (PR) : Refined RECIST | 56 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Incomplete Form : Refined RECIST | 16 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Progressive Disease (PD) : RECIST 1.1 | 13 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Not Evaluable : RECIST 1.1 | 8 Number of Responses (RECIST 1.1+RRECIST) |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver | Progressive Disease (PD) : Refined RECIST | 13 Number of Responses (RECIST 1.1+RRECIST) |
Secondary
Overall Survival
The outcome was not analyzed due to unreliability of the clinical database.
Time frame: From date of randomization until the date of death from any cause, assessed up to 36 months.
Population: Overall survival data assessed until 36 months can be calculated for 42 CIS GEM participants and 36 SIRT+CIS GEM participants due to early termination and database errors. The validity and reliability of these data are not complete.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemotherapy (Cisplatin-Gemcitabine) | Overall Survival | Number of Participants Alive | 14 Participants |
| Chemotherapy (Cisplatin-Gemcitabine) | Overall Survival | Number of Participants Expired | 28 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Overall Survival | Number of Participants Expired | 24 Participants |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Overall Survival | Number of Participants Alive | 12 Participants |
Secondary
Progression Free Survival (PFS) at Any Site
PFS was defined as the time interval between randomization and the date of tumor progression. Diagnosis of tumor progression was to be made using RECIST 1.1. The outcome was not analyzed due to unreliability of the clinical database.
Time frame: From date of randomization to the date of progression at any site until the first date of documented tumor progression at any site or date of death from any cause, assessed up to 36 months.
Population: The data set we received for analysis showed 38 CIS-GEM participants and 27 SIRT+CIS GEM participants with reported tumor progression data available for any site. Due to database issues, the validity and reliability of this data is not complete
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chemotherapy (Cisplatin-Gemcitabine) | Progression Free Survival (PFS) at Any Site | 332 Days to tumor progression |
| Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine) | Progression Free Survival (PFS) at Any Site | 424 Days to tumor progression |