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

NCT03086993 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: PHP-ICC-203
• Study Type: interventional
• Target: 295
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Bile Duct Cancer; Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Patients will be followed until death

  Change in survival is being assessed through study completion, an average of 2 years

Secondary Outcomes (2)

• Progression-free survival, as determined by IRC

  Change in PFS change will be assessed every 9 weeks through study completion, an average of 1 year

• Objective response rate (CR + PR) as determined by the Investigator

  ORR change will be assessed every 9 weeks through study completion, an average of 1 year

Other Outcomes (8)

• Progression-free survival, as determined by the Investigator

  PFS change will be assessed every 9 weeks through study completion, an average of 1 year

• Objective response rate as determined by IRC

  ORR change will assessed every 9 weeks through study completion, an average of one year

• Quality of Life (QOL) as measured by the functional health survey EQ-5D module

  QOL change will be evaluated every 6 weeks through study completion, an average of 1 year

Study Arms (2)

Melphalan/PHP

EXPERIMENTAL

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

Cisplatin and Gemcitabine

ACTIVE COMPARATOR

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

Interventions

Melphalan/HDS COMBINATION_PRODUCT

Melphalan/HDS treatment for up to six cycles, followed by a re-induction of CisGem.

Also known as: Melphalan/PHP

Melphalan/PHP

Cisplatin and Gemcitabine DRUG

continuous treatment with Cis/Gem until disease progression

Also known as: Cis/Gem

Cisplatin and Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are willing and able to provide signed informed consent.
• Intrahepatic cholangiocarcinoma diagnosed by histology.
• 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
• 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.
• At least one target lesion based on the evaluation criteria in solid tumors (RECIST 1.1).
• Patients must have an ECOG PS of 0-1 at screening.
• Male or female patients aged ≥ 18 years.
• 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).

You may not qualify if:

• Greater than 50% tumor burden in the liver by imaging.
• 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.
• History of, or known, hypersensitivity to any components of melphalan or the components of the Melphalan/HDS system.
• History of, or known, hypersensitivity to gemcitabine or platinum-containing compounds.
• Known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia.
• Prior treatment with gemcitabine or platinum-containing compounds, including in the adjuvant setting.
• Received an investigational agent for any indication within 30 days prior to first treatment.
• 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.
• 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.
• 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.
• History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.
• 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).
• 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).
• 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).
• 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).

Sponsors & Collaborators

• Delcath Systems Inc.: lead

Study Sites (3)

Duke Health

Durham, North Carolina, 27710, United States

Location

Ohio State University/Teaching Hospital

Columbus, Ohio, 43210, United States

Location

West Cancer Center

Memphis, Tennessee, 38120, United States

Location

MeSH Terms

Conditions

Bile Duct Neoplasms; Cholangiocarcinoma

Interventions

Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2017
• First Posted: March 22, 2017
• Study Start: April 10, 2018
• Primary Completion: January 1, 2023
• Study Completion: May 1, 2023
• Last Updated: March 24, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)