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Phase Ib Study of the Safety and Pharmacokinetics of Chemoembolization With Irinotecan-Eluting Beads for the Treatment of Hepatic Metastases

Phase 1
18 Years
84 Years
Open (Enrolling)
Neoplasm Metastases, Melanoma, Colorectal Neoplasms

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Trial Information

Phase Ib Study of the Safety and Pharmacokinetics of Chemoembolization With Irinotecan-Eluting Beads for the Treatment of Hepatic Metastases


- Clinical evidence suggests that hepatic chemoembolization may prolong survival in
patients with hepatic metastases.

- Early studies have indicated that chemoembolization using irinotecan drug eluting beads
may be more effective in treating hepatic metastases from colon or melanoma primary


- Primary Objective:

--To determine the safety of hepatic chemoembolization with drug-eluting beads
containing 100mg of irinotecan

- Secondary Objectives:

- To determine the serum pharmacokinetics and tumor tissue concentrations achieved
following hepatic chemoembolization with irinotecan-eluting beads


- Patients > 18 years of age with pathologically proven hepatic metastases from the
gastrointestinal tract, or melanoma with unresectable hepatic lesions.

- Patients whose extent of hepatic metastases represents < 60% of total liver volume AND
whose extrahepatic metastatic disease is determined to be minimal

- Patients must be ECOG performance status of less than or equal to 2 and a life
expectancy of more than 3 months.

- Patients must have adequate organ function.

- Patients must not have had chemotherapy, radiation therapy, or biological therapy for
at least 4 weeks prior to starting study treatments.

- Patients are not to receive conventional chemotherapy or therapeutic monoclonal
antibodies while on study.

- Patients must not have an acute, critical illness.


- A Phase Ib trial in which patients undergo hepatic chemoembolization with drug-eluting
beads containing 100mg irinotecan.

- Up to 15 patients will be enrolled over 1 year to accrue 10 evaluable patients.

- Patients will undergo up to 3 chemoembolizations.

- Following chemoembolization, patients will have serial serum pharmacokinetic samples
drawn and tumor biopsies in order to measure serum and tumor tissue concentrations of

- Patients will be followed for one year after completion of the last treatment.

Inclusion Criteria


- Patients with pathologically proven hepatic-dominant metastases from abdominal or
gastrointestinal tract primary malignancy or melanoma where the life limiting
component of the disease is hepatic metastasis

- Patients must have unresectable hepatic lesions or must be unable or unwilling to
undergo surgical resection. Patients may have undergone prior wedge resection of the
liver for metastatic disease

- All patients must be refractory to or intolerant of approved standard systemic


- Patients with metastatic colorectal must have received 5-FU and leucovorin in
combination with either oxaliplatin and/or irinotecan, since level 1 evidence support
increase survival with these regimens, compared to 5-FU and leucovorin alone.

- Patients with melanoma must have received IL-2 or other immunotherapy options (such
as ipilimumab or adoptive cell therapy) that have been reported to have efficacy.

- Patients with extrahepatic metastases or an unresected primary lesion will be
considered eligible if the extrahepatic disease is minimal

- Extent of hepatic metastases is < 60% of total hepatic volume.

- Patients must have at least one lesion that can be readily biopsied (at least
10mm diameter)

- ECOG performance status less than or equal to 2

- Life expectancy > 3 months

- At least 18 years of age

- Age < 85 years

- Patients must have had no chemotherapy, radiotherapy, or biologic therapy for
their malignancy for at least 4 weeks (or until response can be adequately
assessed) prior to treatment and must have recovered from all clinically
significant side effects of therapeutic and diagnostic interventions. Anti-VEGF
agents (eg, Avastin) may not be administered less than 4 weeks prior to DEB-TACE

- Patients are not to receive conventional chemotherapy or therapeutic monoclonal
antibodies while receiving protocol treatment

- Hematology:

- Absolute neutrophil count greater than 1500/mm(3) without the support of Filgrastim.

- Platelet count greater than 75,000/mm(3).

- Hemoglobin greater than 8.0 g/dl.


- Serum ALT/AST less than or equal to 3 times the upper limit of normal.

- Serum creatinine less than or equal to 2.0 mg/dl unless the measured creatinine
clearance is greater than 60 mL/min

- Total bilirubin less than or equal to 2 mg/dl.

- INR < 1.5

- PTT less than or equal to 1.3 times control unless a mixing study confirms the
presence of a lupus anticoagulant as the cause for the prolonged PTT.

- Screening electrocardiogram is normal with QTc less than or equal to 480msec).


- Significant cardiac or pulmonary insufficiency as evidenced by

- history of congestive heart failure with an LVEF < 40%

- history of COPD or other chronic pulmonary disease with PFT's indicating an FEV1
less than 30% or a DLCO less than 40% predicted for age

- Portal Vein Occlusion or other contraindications to chemoembolization

- Inflammatory bowel disease

- Prior chemoembolization therapy

- Prior precutaneous hepatic perfusion therapy

- Prior selective internal radiation therapy (SIRT) with Yttrium-90

- Prior biliary diversion surgery

- Previous liver resection other than wedge resection.

- Pregnant patients and nursing mothers will be excluded because of the unknown effects
of this therapy on the fetus or nursing infants.

- Patients taking immunosuppressive drugs or requiring ongoing chronic anticoagulation
will not be eligible.

- Patients with active bacterial infections with systemic manifestations (malaise,
fever, leucocytosis) are not eligible until completion of appropriate therapy.

- Patients with severe allergic reactions to iodine contrast which cannot be controlled
by premedication with antihistamines and steroids are not eligible as a hepatic
angiogram is needed for this procedure.

- Patients with a known prior hypersensitivity reaction or other contraindication to
irinotecan will be excluded.

- Patients taking phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, St.
John's Wort, or other CYP3A inducers or inhibitors are not eligible for this study.

- Patients are prohibited from receiving other experimental agents/adjuvant treatments
during the study.

- Patients with more than one active primary malignancy, except for basal cell
carcinoma or superficial bladder neoplasia, are to be excluded.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the safety of hepatic chemoembolization with drug-eluting beads containing 100mg of irinotecan

Principal Investigator

Elliot B Levy, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institutes of Health Clinical Center (CC)


United States: Federal Government

Study ID:




Start Date:

March 2011

Completion Date:

Related Keywords:

  • Neoplasm Metastases
  • Melanoma
  • Colorectal Neoplasms
  • Chemoembolization
  • Hepatic Metastases
  • Irinotecan
  • Drug Eluding Beads
  • Colorectal Cancer
  • Liver Cancer
  • Hepatic Cancer
  • Melanoma
  • Neoplasms
  • Colorectal Neoplasms
  • Liver Neoplasms
  • Melanoma
  • Neoplasm Metastasis



National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892