Safety and Pharmacokinetics of Treating Liver Cancer With Drug-Eluting Beads

NCT01336985 | Terminated Phase 1

• 2 other identifiers: 11013111-CC-0131
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Cancers in other parts of the body often spread to the liver, developing tumors which in many instances cannot be removed with surgery. Liver chemoembolization is a treatment that is routinely performed to control liver tumors in those who cannot have surgery. It has been shown to prolong survival, but does not cure the cancer. During chemoembolization very tiny beads (drug-eluting beads, or DEB) containing chemotherapy drugs (usually doxorubicin) are administered directly into the blood vessels of a liver tumor. The drug within the beads is then released into the tumor whilethe beads temporarily interrupt the tumor s blood supply.
• Irinotecan, a drug commonly given intravenously to treat colon cancer, has been given in chemoembolization procedures in four other studies that have shown that the treatment is generally well tolerated. Researchers are interested in determining whether giving the drug irinotecan directly into the liver using drug-eluting beads is not only well tolerated but also provides a larger dose directly to the tumor as determined by tumor and normal liver tissue biopsies. The liver biopsies are an optional portion of the study. Objectives: \- To evaluate the safety and effectiveness of chemoembolization with irinotecan for tumors caused by cancer that has spread to the liver. Eligibility: \- Individuals at least 18 years of age who have melanoma, colon, or another intra-abdominal cancer that has spread to the liver. Design:
• Participants will be screened with a physical examination, medical history, blood tests, tumor imaging studies, and liver biopsies.
• Participants will receive up to 3 DEB chemoembolization treatments about 6 weeks apart.
• After two treatments, participants will have imaging studies to see if the tumors have shrunk, and those whose tumors have shrunk may have a third treatment.
• Multiple liver biopsies may be performed and blood samples will be taken to determine how much drug is in the tumor and the circulation, and to see how the tumor reacts to the drug.
• Participants will return for followup visits for up to 1 year....

Conditions

Neoplasm Metastases; Melanoma; Colorectal Neoplasms

Keywords

Chemoembolization; Hepatic Metastases; Irinotecan; Drug Eluding Beads; Colorectal Cancer; Liver Cancer; Hepatic Cancer; Melanoma

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (1)

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

Interventions

Irinotecan DRUG

Chemoembolization PROCEDURE

Drug-Eluting Beads DEVICE

Biopsy PROCEDURE

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 therapy.
• Specifically:
• 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 treatment.
• Patients are not to receive conventional chemotherapy or therapeutic monoclonal antibodies while receiving protocol treatment

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, Giacchetti S, Paule B, Kunstlinger F, Ghemard O, Levi F, Bismuth H. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004 Oct;240(4):644-57; discussion 657-8. doi: 10.1097/01.sla.0000141198.92114.f6.

  PMID: 15383792 BACKGROUND

• Adam R. Chemotherapy and surgery: new perspectives on the treatment of unresectable liver metastases. Ann Oncol. 2003;14 Suppl 2:ii13-6. doi: 10.1093/annonc/mdg731.

  PMID: 12810452 BACKGROUND

• Aliberti C, Tilli M, Benea G, Fiorentini G. Trans-arterial chemoembolization (TACE) of liver metastases from colorectal cancer using irinotecan-eluting beads: preliminary results. Anticancer Res. 2006 Sep-Oct;26(5B):3793-5.

  PMID: 17094403 BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis; Melanoma; Colorectal Neoplasms; Liver Neoplasms

Interventions

Irinotecan; Chemoembolization, Therapeutic; Biopsy

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Embolization, Therapeutic; Hemostatic Techniques; Therapeutics; Therapeutic Occlusion; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Elliot B Levy, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: April 14, 2011
• First Posted: April 18, 2011
• Study Start: March 28, 2011
• Study Completion: March 28, 2011
• Last Updated: December 17, 2019

Record last verified: 2014-11-03

Locations

US (1)