Percutaneous Hepatic Perfusion vs. Cisplatin/Gemcitabine in Patients With Intrahepatic Cholangiocarcinoma
|Bile Duct Cancer Intrahepatic Cholangiocarcinoma||Combination Product: Melphalan/HDS Drug: Cisplatin and Gemcitabine||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Randomized, Controlled Study to Compare the Efficacy, Safety and Pharmacokinetics of Melphalan/HDS Treatment Given Sequentially Following Cisplatin/Gemcitabine Versus Cisplatin/Gemcitabine in Patients With IntraHepatic Cholangiocarcinoma|
- Overall Survival [ Time Frame: Change in survival is being assessed through study completion, an average of 2 years ]Patients will be followed until death
- Progression-free survival, as determined by IRC [ Time Frame: Change in PFS change will be assessed every 9 weeks through study completion, an average of 1 year ]Period of time from 1st treatment to tumor progression or death
- Objective response rate (CR + PR) as determined by the Investigator [ Time Frame: ORR change will be assessed every 9 weeks through study completion, an average of 1 year ]The number of patients with either a complete or partial response as determined by the investigator
- Progression-free survival, as determined by the Investigator [ Time Frame: PFS change will be assessed every 9 weeks through study completion, an average of 1 year ]Period of time from 1st treatment to tumor progression
- Objective response rate as determined by IRC [ Time Frame: ORR change will assessed every 9 weeks through study completion, an average of one year ]The number of patients with either a complete or partial response as determined by the IRC
- Quality of Life (QOL) as measured by the functional health survey EQ-5D module [ Time Frame: QOL change will be evaluated every 6 weeks through study completion, an average of 1 year ]QoL will be evaluated for all patients treated in the study
- Pharmacokinetic Outcome Measures: Cmax [ Time Frame: PK is assessed at each Melphalan/HDS cycle approximately every 6 weeks for an average of one year ]Observed maximum concentration (Cmax)
- Pharmacokinetic Outcome Measures: AUC [ Time Frame: PK is assessed at each Melphalan/HDS cycle approximately every 6 weeks for an average of one year ]Area under the curve (AUC)
- Pharmacokinetic Outcome Measures: Tmax [ Time Frame: PK is assessed at each Melphalan/HDS cycle approximately every 6 weeks for an average of one year ]Time of maximum concentration (Tmax)
- Pharmacokinetic Outcome Measures: CL [ Time Frame: PK is assessed at each Melphalan/HDS cycle approximately every 6 weeks for an average of one year ]Total system clearance (CL)
- Incidence of Treatment-Emergent Adverse Events (Safety) [ Time Frame: Adverse events are assessed from time of informed consent through the study completion, average about 1 year ]Number of patients experiencing treatment related adverse events as assessed by CTCAE version 4.0
|Anticipated Study Start Date:||December 2017|
|Estimated Study Completion Date:||May 2023|
|Estimated Primary Completion Date:||January 2023 (Final data collection date for primary outcome measure)|
Patients may receive up to 6 treatments of Melphalan/HDS 3.0 mg/kg IBW. Each treatment cycle consists of 6 weeks with an acceptable delay for an additional 2 weeks (i.e. 8 weeks in total). The maximum dose of melphalan will be 220 mg per treatment.
Combination Product: Melphalan/HDS
Melphalan/HDS treatment for up to six cycles, followed by a re-induction of CisGem.
Other Name: Melphalan/PHP
Active Comparator: Cisplatin and Gemcitabine
Each Cis/Gem treatment cycle will comprise cisplatin, dosed at 25 mg per square meter of body surface area, and gemcitabine, dosed at 1000 mg per square meter of body surface area. Each will be administered on Days 1 and 8 every 3 weeks.
Drug: Cisplatin and Gemcitabine
continuous treatment with Cis/Gem until disease progression
Other Name: Cis/Gem
The study will consist of 4 phases: a screening, an induction, randomization and follow-up phase.
Screening phase: Screening assessments will be conducted within 28 days prior to initiation of Induction Phase treatment to determine each patient's overall eligibility. These assessments will include medical history; physical examination; Eastern Cooperative Oncology Group (ECOG) performance status (PS); 12 lead electrocardiogram (ECG); echocardiogram (ECHO); vital signs; laboratory assessments; radiologic assessments of disease status; and an evaluation of the vasculature compatibility for Percutaneous Hepatic Perfusion (PHP).
Induction phase: The initial 12 weeks of the study, all patients will receive 4 cycles of cisplatin/gemcitabine. Each cycle will be comprised of cisplatin dosed at 25 mg per square meter of body-surface area (BSA), followed by gemcitabine dosed at 1000 mg per square meter of BSA; dosing will occur on Days 1 and 8 of each cycle. At the completion of 3 cycles (week 8 (+1 week)) of cisplatin/gemcitabine, an imaging scan is performed as per standard of care to determine if the patient has progressed on treatment or should continue receiving the cisplatin/gemcitabine induction therapy for one more cycle (4th cycle - prior to randomization). At the completion of 4 cycles (week 12 (+1 week)) of cisplatin/gemcitabine, patients will undergo whole-body imaging to determine the status of their disease. Patients with progressive disease (PD) will be discontinued from study treatment, and will receive further treatment to be determined by the principal investigator (PI). They will continue to be followed until death or the end of the study. Patients who have at least stable disease (SD) at imaging after induction phase of 4 cycles of cisplatin/gemcitabine (week 12 (+ 1 week)) will go on to the next phase of the study (Randomized Treatment Phase).
Randomization phase: Patients who have at least stable disease via imaging at the end of the Induction Phase will be randomized in a 1:1 ratio to Melphalan/HDS treatment or to continue cisplatin/gemcitabine in cycles previously described in the Induction Phase, until progressive disease (PD) or unacceptable toxicity is observed. Patients who were randomized to treatment with Melphalan/HDS (dosed at 3.0 mg/kg Ideal Body Weight [IBW]) must undergo their first treatment within 14 days following the whole body imaging performed at end of the Induction Phase. For Melphalan/HDS treatment, patients will receive up to 6 treatments. Each treatment cycle will consist of 6 weeks with an acceptable delay for up to another 2 weeks before the next planned treatment to allow for additional recovery, if needed. After the Melphalan/HDS treatment, in the absence of disease progression, the patient should undergo a re-induction of CisGem. Tumor response will be assessed in both treatment arms every 8 weeks (+ 1 week) until PD.
The assessment scans will be reviewed by Independent Review Committee (IRC). At any time when PD is observed, the patient will be removed from further study treatment; any further treatment will be at the discretion of the investigator. Melphalan/HDS treatment will also be discontinued in the event that recovery requires more than 8 weeks from last treatment. An end-of-treatment visit will be conducted approximately 6 to 8 weeks following the final dose of study treatment. Ongoing adverse events (AEs) at the end-of-treatment visit will be followed until the severity returns to common terminology criteria for adverse events (CTCAE) Grade < 1.
Follow-up phase: In the event that disease has not progressed at the end-of-treatment visit, disease assessment scans will continue every 8 weeks (+ 1 week) until PD is documented. Patients will be contacted by phone every 6 months for survival status for the first two years following the completion of study treatment, then yearly thereafter until death, withdrawal of informed consent or they become lost to follow-up, whichever occurs first. Patients will be monitored for two years following the completion of study treatment for the development of myelodysplasia and secondary leukemia.
Please refer to this study by its ClinicalTrials.gov identifier: NCT03086993
|Contact: LESLIE CALLAHAN, BSN, MS||212-489-2100 ext 247||LCALLAHAN@DELCATH.COM|
|Contact: LARS BIRGERSON, MDemail@example.com|