TKM 080301 for Primary or Secondary Liver Cancer
A Phase 1 Dose Escalation Study of Hepatic Intra-Arterial Administration of TKM 080301 (Lipid Nanoparticles Containing siRNA Against the PLK1 Gene Product) in Patients With Colorectal, Pancreas, Gastric, Breast, Ovarian and Esophageal Cancers With Hepatic
2 other identifiers
interventional
1
1 country
1
Brief Summary
Background: Cancer in the liver can start in the liver (e.g., primary liver cancer or hepatocellular cancer) or spread to the liver from cancers in other parts of the body (e.g. colon, pancreas, gastric, breast, ovarian, esophageal cancers, cancer with metastases to the liver.) People who have tumors that can be removed by surgery live longer than those whose cancer cannot be removed. Chemotherapy can shrink some tumors in the liver, which also helps people to live longer, and sometimes chemotherapy can shrink tumors enough that they can be removed by surgery. However, most chemotherapy drugs do not work well on tumors in the liver. In this study we are testing a new drug, TKM-080301, given directly into the cancer blood supply in the liver circulation, to see if it will cause tumors to shrink. Objectives: \- To test the safety and effectiveness of TKM-080301 for cancer in the liver that has not responded to standard treatments. Eligibility: \- Individuals at least 18 years of age who have inoperable cancer that has started in or spread to the liver. Design:
- Participants will be screened with a medical history and physical exam. They will also have blood tests, and imaging studies.
- Participants will have a liver angiogram (type of X-ray study) to look at the blood flow in the liver and to place a catheter for delivery of the TKM080301.
- Participants will have a single dose of TKM-080301 given directly into the liver. After the drug has been given, the catheter will be removed. They will have frequent blood tests and keep a diary to record side effects.
- Participants may have two more doses, each dose given 2 weeks apart. {Before each dose, participants will have another angiogram and catheter placement.}They may also have liver biopsies to study the tumors.
- Two weeks after the third treatment (one full course), participants will have a physical exam, blood tests, and imaging studies. If the tumor is shrinking, they may have up to three more courses of the study drug.
- Participants will have follow up visits every 3 months for 2 years after the last course and then every 6 months as required.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Aug 2011
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 26, 2011
CompletedFirst Submitted
Initial submission to the registry
September 16, 2011
CompletedFirst Posted
Study publicly available on registry
September 20, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 21, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
June 21, 2012
CompletedAugust 3, 2018
October 9, 2012
10 months
September 16, 2011
August 2, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To evaluate feasibility of administering TKM-080301 via HAI, and establish MTD and DLT.
2 years
Secondary Outcomes (3)
Characterize PK & pharmacodynamics of TKM 080301
2 years
Eval biological effects of TKM-080301 on biopsies performed before & after 1 cycle of tx
2 years
To evaluate the potential conversion rate from unresectable to resectable disease.
2.5 years
Interventions
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed colorectal, pancreas, gastric, breast, ovarian and esophageal cancers with hepatic metastases, or primary liver cancers (Hepatocellular carcinoma and Cholangiocarcinoma).
- Hepatic disease must be measurable per RECIST Criteria (version 1.1).
- Hepatic disease should be deemed unresectable as per standard of care criteria.
- Note: Evidence of limited unresectable extrahepatic disease on preoperative radiological studies is acceptable if the life-limiting component of progressive disease is in the liver.
- All patients must have failed to respond to standard regimens or therapies known to provide clinical benefit. For example:
- \- Patients with metastatic colorectal cancer must have received 5-FU and
- leucovorin in combination with either oxaliplatin and/or irinotecan, since level
- evidence support increase survival with these regimens, compared to 5-FU and leucovorin alone.
- \- Patients with hepatocellular carcinoma must have received sorafenib, since level 1 evidence support increase survival.
- Greater than or equal to 18 years of age
- Must be able to understand and sign the Informed Consent Document
- Clinical performance status of ECOG less than or equal to 2
- Life expectancy of greater/equal than two months
- Patients of both genders must be willing to practice birth control during and for four months after receiving chemotherapy
- Hematology:
- +14 more criteria
You may not qualify if:
- Any known brain metastases (prior or current regardless of treatment status)
- Women of child-bearing potential who are pregnant or breastfeeding, because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune systems, recent myocardial infarction or heart failure (within 6 months of enrollment).
- NYHA greater than or equal to 2
- Childs B or C cirrhosis or with evidence of severe portal hypertension by history, endoscopy, or radiologic studies
- Weight less than 40 kg
- Significant ascites, greater than 1000cc in the absence of peritoneal disease
- Concomitant medical problems that would place the patient at an unacceptable risk for the procedure/drug
- Patient has known hypersensitivity or previous severe reactions to oligonucleotideor lipid-based products, including liposomal drug products (e.g. Doxil) and phospholipid-based products (parenteral nutrition, Intralipid)
- Discretion of the PI
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (3)
Steegmaier M, Hoffmann M, Baum A, Lenart P, Petronczki M, Krssak M, Gurtler U, Garin-Chesa P, Lieb S, Quant J, Grauert M, Adolf GR, Kraut N, Peters JM, Rettig WJ. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Curr Biol. 2007 Feb 20;17(4):316-22. doi: 10.1016/j.cub.2006.12.037. Epub 2007 Feb 8.
PMID: 17291758BACKGROUNDBarr FA, Sillje HH, Nigg EA. Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol. 2004 Jun;5(6):429-40. doi: 10.1038/nrm1401. No abstract available.
PMID: 15173822BACKGROUNDStrebhardt K, Ullrich A. Targeting polo-like kinase 1 for cancer therapy. Nat Rev Cancer. 2006 Apr;6(4):321-30. doi: 10.1038/nrc1841.
PMID: 16557283BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Udo Rudloff, M.D.
National Cancer Institute (NCI)
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
September 16, 2011
First Posted
September 20, 2011
Study Start
August 26, 2011
Primary Completion
June 21, 2012
Study Completion
June 21, 2012
Last Updated
August 3, 2018
Record last verified: 2012-10-09