Clinical Trials /

Percutaneous Hepatic Perfusion vs. Cisplatin/Gemcitabine in Patients With Intrahepatic Cholangiocarcinoma

NCT03086993

Description:

This study will evaluate two groups of patients who have intrahepatic cholangiocarcinoma. Each group will receive induction treatment with Cisplatin and Gemcitabine per SOC for 4 treatment cycles. Following induction treatment patients will be randomize (1:1), to 2 arms of treatment. One group (50%) will be receive high dose chemotherapy delivered specifically to the liver, while the other group (50%) will continue treatment with Cisplatin and Gemcitabine. Patient in each group will get repeating cycles of treatment until the cancer advances. All patients will be followed until death. This study will compare the overall survival (OS) in patients with intrahepatic cholangiocarcinoma.

Related Conditions:
  • Intrahepatic Cholangiocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Percutaneous Hepatic Perfusion vs. Cisplatin/Gemcitabine in Patients With Intrahepatic Cholangiocarcinoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: PHP-ICC-203
  • NCT ID: NCT03086993

Conditions

  • Bile Duct Cancer
  • Intrahepatic Cholangiocarcinoma

Interventions

DrugSynonymsArms
Cisplatin and GemcitabineCis/GemCisplatin and Gemcitabine

Purpose

This study will evaluate two groups of patients who have intrahepatic cholangiocarcinoma. Each group will receive induction treatment with Cisplatin and Gemcitabine per SOC for 4 treatment cycles. Following induction treatment patients will be randomize (1:1), to 2 arms of treatment. One group (50%) will be receive high dose chemotherapy delivered specifically to the liver, while the other group (50%) will continue treatment with Cisplatin and Gemcitabine. Patient in each group will get repeating cycles of treatment until the cancer advances. All patients will be followed until death. This study will compare the overall survival (OS) in patients with intrahepatic cholangiocarcinoma.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Melphalan/PHPExperimentalPatients 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.
    Cisplatin and GemcitabineActive ComparatorEach 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.
    • Cisplatin and Gemcitabine

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Are willing and able to provide signed informed consent.
    
              2. Intrahepatic cholangiocarcinoma diagnosed by histology.
    
              3. Unresectable ICC, with less than 50% of the liver involved, and without clinically
                 significant extra-hepatic disease (regional lymph node lesions [≤ 2 cm] are
                 acceptable) based on CT
    
              4. Scans used to determine eligibility (CT scan of the chest/abdomen/pelvis and liver)
                 must be performed within 28 days prior to initiation of Induction Phase treatment.
    
              5. At least one target lesion based on the evaluation criteria in solid tumors (RECIST
                 1.1).
    
              6. Patients must have an ECOG PS of 0-1 at screening.
    
              7. Male or female patients aged ≥ 18 years.
    
              8. Patients must weigh ≥ 35 kg (due to possible size limitations with respect to
                 percutaneous catheterization of the femoral artery and vein using the Delcath Hepatic
                 Delivery System).
    
            Exclusion Criteria:
    
              1. Greater than 50% tumor burden in the liver by imaging.
    
              2. History of orthotopic liver transplantation, hepatic vasculature incompatible with
                 perfusion, hepatofugal flow in the portal vein or known unresolved venous shunting.
                 Prior Whipple procedure is permitted provided the anatomy is still compatible for
                 perfusion with the Melphalan/HDS system.
    
              3. History of, or known, hypersensitivity to any components of melphalan or the
                 components of the Melphalan/HDS system.
    
              4. History of, or known, hypersensitivity to gemcitabine or platinum-containing
                 compounds.
    
              5. Known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia.
    
              6. Prior treatment with gemcitabine or platinum-containing compounds, including in the
                 adjuvant setting.
    
              7. Received an investigational agent for any indication within 30 days prior to first
                 treatment.
    
              8. Prior radiation therapy to the liver including 90Y , I131 based loco regional therapy.
                 Prior loco regional therapy, including resection, based on other technology for ICC,
                 if any, must have been completed at least 4 weeks prior to baseline imaging.
    
              9. Not recovered from side effects of prior therapy to ≤ Grade 1 (according to National
                 Cancer Institute [NCI] CTCAE version 4.03). Certain side effects that are unlikely to
                 develop into serious or life-threatening events (e.g. alopecia) are allowed at > Grade
                 1.
    
             10. Those with New York Heart Association functional classification II, III or IV; active
                 cardiac conditions including unstable coronary syndromes (unstable or severe angina,
                 recent myocardial infarction), worsening or new-onset congestive heart failure,
                 significant arrhythmias and severe valvular disease must be evaluated for risks of
                 undergoing general anesthesia.
    
             11. History or evidence of clinically significant pulmonary disease that precludes the use
                 of general anesthesia.
    
             12. Any evidence of severe or uncontrolled systemic diseases which, in the view of the
                 investigator, makes it undesirable for the patient to participate in the trial (e.g.
                 unstable or uncompensated respiratory, cardiac, hepatic or renal disease).
    
             13. Patients with active bacterial infections with systemic manifestations (malaise,
                 fever, leukocytosis) are not eligible until completion of appropriate therapy.
                 Patients taking low-dose antibiotics for biliary obstruction are exempted from this
                 exclusion criterion.
    
             14. History of prior malignancy that will interfere with the response evaluation
                 (exceptions include in-situ carcinoma of the cervix treated by cone-biopsy/resection,
                 non-metastatic basal and/or squamous cell carcinomas of the skin, any early stage
                 (stage I) malignancy adequately resected for cure greater than 5 years previously).
    
             15. Acute or active hepatitis B or hepatitis C infection. Patients with anti-hepatitis B
                 core antigen (HBc) positive, or hepatitis B surface antigen (HBsAg) but viral
                 deoxyribonucleic acid (DNA) negative are exception(s).
    
             16. History of bleeding disorders which would put a patient at risk for bleeding with
                 anti-coagulation or patients with an increased risk of thromboembolic or hemorrhagic
                 events (e.g., stroke).
    
             17. Brain lesions or intracranial abnormalities at risk for bleeding, by history or
                 radiologic imaging (e.g., active metastases).
    
             18. Known varices at risk of bleeding, including medium or large esophageal or gastric
                 varices, or active peptic ulcer.
    
             19. Inadequate hematologic function as evidenced by any of the following:
    
                   1. Platelets < 100,000/µL
    
                   2. Hemoglobin < 10.0 g/dL, independent of transfusion or growth factor support
    
                   3. White blood cell count (WBC) < 2,000/µL
    
                   4. Neutrophils < 1,500 cells/µL.
    
             20. Serum creatinine > 1.5 mg/dL. If serum creatinine > 1.5 mg/dL, the measured creatinine
                 clearance must be measured and patient is eligible if creatinine clearance > 45
                 mL/min.
    
             21. Inadequate liver function as evidenced by any of the following:
    
                   1. Total serum bilirubin > 1.5 times ULN
    
                   2. Aspartate aminotransferase (AST) > 5 times the upper limit of normal (ULN) or
                      alanine aminotransferase (ALT) > 5 times ULN
    
                   3. Serum albumin < 2.9 g/dL.
    
             22. Known alcohol or drug abuse that would preclude compliance with study procedures.
    
             23. For female patients of childbearing potential (defined as having had a menstrual
                 period within the past 12 months): a positive serum pregnancy test (β-human chorionic
                 gonadotropin [β HCG]) within 7 days prior to enrollment; or unwilling or unable to
                 undergo hormonal suppression to avoid menstruation during treatment; or if
                 breastfeeding, unwilling or unable to stop breastfeeding while on study treatment.
    
             24. Sexually active females of childbearing potential and sexually active males with
                 partners of reproductive potential: unwilling or unable to use appropriate
                 contraception from screening until at least 6 months after last administration of
                 study treatment.
    
             25. Patients taking immunosuppressive drugs or who are unable to be temporarily removed
                 from chronic anti-coagulation therapy.
    
             26. Patients with biliary stents.
    
             27. Patients with a history of external percutaneous transhepatic cholangiography catheter
                 placement.
    
             28. Patients previously treated with any intra-arterial regional hepatic therapy such as
                 trans-arterial chemoembolization.
    
             29. Patients with severe allergic reactions to iodine contrast which cannot be controlled
                 by premedication with antihistamines and steroids.
    
             30. Patients with a latex allergy
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall Survival
    Time Frame:Change in survival is being assessed through study completion, an average of 2 years
    Safety Issue:
    Description:Patients will be followed until death

    Secondary Outcome Measures

    Measure: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
    Safety Issue:
    Description:Period of time from 1st treatment to tumor progression or death
    Measure: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
    Safety Issue:
    Description:The number of patients with either a complete or partial response as determined by the investigator

    Details

    Phase:Phase 2/Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Delcath Systems Inc.

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