Colorectal Cancer With Hepatic MetastasesPhase 1NCT01437007
TKM 080301 for Primary or Secondary Liver Cancer
A Phase 1 study testing TKM-080301 in people with Colorectal Cancer With Hepatic Metastases and Pancreas Cancer With Hepatic Metastase, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Colorectal Cancer With Hepatic Metastases, Pancreas Cancer With Hepatic Metastase, Gastric Cancer With Hepatic Metastase
- What is being tested?
- TKM-080301
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Aug 2011to 21 Jun 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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
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.
Read more
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.
Read the detailed description
BACKGROUND:
- Metastatic liver disease is a life-limiting factor for patients with a variety of cancers. For unresectable liver metastases, the 5-year survival is < 5%.
- For selected histologies the 5-year survival of resectable hepatic metastases ranges from 20-60%, suggesting that control of liver metastases could result in prolonged survival.
- Phase I through III trials have shown that Hepatic Arterial Infusion (HAI) is safe. However, agents used thus far in HAI have limited efficacy.
- TKM-080301 is a lipid nanoparticle (LNP) formulation containing siRNA against the PLK1 (polo-like kinase-1) gene product. More specifically, TKM-080301 is a type of LNP formulation, referred to as SNALP (Stable Nucleic Acid Lipid Particles). PLK1 has been validated as a molecular target and a prognostic factor in a variety of cancers. Inhibition of PLK1 activity in proliferating cancer cells rapidly induces mitotic arrest and apoptosis.
- This study will offer HAI with TKM-080301 to patients with unresectable and/or life threatening primary liver cancer or liver metastases.
OBJECTIVES:
Primary Objective:
- To evaluate feasibility of administering TKM-080301 via HAI and to characterize the pharmacokinetics (PK) and pharmacodynamics of TKM-080301 administered by HAI.
Secondary Objectives:
- To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of TKM-080301.
- To evaluate response rate using RECIST, PET and EASL criteria.
- To evaluate the conversion rate from unresectable to resectable disease.
ELIGIBILITY:
- Patients with unresectable colorectal, pancreas, gastric, breast, ovarian and esophageal cancers with hepatic metastases; or primary liver cancer patients who have demonstrated progressive disease following standard of care treatment.
- 18 years old or greater with an ECOG 0-2
- Laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to surgery or chemotherapy.
DESIGN:
- This is a dose escalation phase-I study testing HAI of TKM-080301 for patients with unresectable colorectal, pancreas, gastric, breast, ovarian and esophageal cancers with hepatic metastases, or primary liver cancers.
- Up to 54 patients who meet eligibility criteria will receive HAI with TKM-080301.
- Initial dose will be 4 mg/m(2); treatment will be given every 2 weeks for up to 12 doses.
- Patients will be evaluated every 6 weeks. Patients whose tumors become resectable will be offered this option; patients who show progressive disease will be taken off treatment. All patients will be followed for survival.
- Conditions
- Colorectal Cancer With Hepatic Metastases, Pancreas Cancer With Hepatic Metastase, Gastric Cancer With Hepatic Metastase, Breast Cancer With Hepatic Metastase, Ovarian Cancer With Hepatic Metastase
- Being tested
- TKM-080301
- Keywords
- SNALP, Regional Therapy, Stage IV Disease, Adenocarcinoma, Unresectable, Liver Metastases, Colorectal Cancer, Stomach Cancer, Gastric Cancer, Breast Cancer, Ovarian Cancer, Pancreatic Cancer, Liver Cancer
- Medical subject headings
- Disease, Adenocarcinoma, Colorectal Neoplasms, Stomach Neoplasms, Breast Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TKM-080301Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate feasibility of administering TKM-080301 via HAI, and establish MTD and DLT.
Measured: 2 years
Secondary outcomes (3)
Characterize PK & pharmacodynamics of TKM 080301
Measured: 2 years
Eval biological effects of TKM-080301 on biopsies performed before & after 1 cycle of tx
Measured: 2 years
To evaluate the potential conversion rate from unresectable to resectable disease.
Measured: 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2011 (estimated)
- Study start26 Aug 2011
- Primary completion21 Jun 2012
- Study completion21 Jun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Colorectal Cancer With Hepatic MetastasesStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Udo Rudloff, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01437007
- Sponsor's protocol ID
- 110240
- Other IDs
- 11-C-0240
- Status last verified
- 9 Oct 2012
- First submitted
- 16 Sep 2011
- Last updated
- 3 Aug 2018
- Results posted
- No
Publications
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.
PubMed 17291758Barr 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.
PubMed 15173822Strebhardt K, Ullrich A. Targeting polo-like kinase 1 for cancer therapy. Nat Rev Cancer. 2006 Apr;6(4):321-30. doi: 10.1038/nrc1841.
PubMed 16557283
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01437007
- Acronym / sponsor ID
- 110240
- Conditions
- Colorectal Cancer With Hepatic Metastases, Pancreas Cancer With Hepatic Metastase, Gastric Cancer With Hepatic Metastase, Breast Cancer With Hepatic Metastase, Ovarian Cancer With Hepatic Metastase
- Keywords
- SNALP, Regional Therapy, Stage IV Disease, Adenocarcinoma, Unresectable, Liver Metastases, Colorectal Cancer, Stomach Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 26 Aug 2011
- Primary completion
- 21 Jun 2012 (actual)
- Study completion
- 21 Jun 2012 (actual)
- First posted
- 20 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
BACKGROUND:
- Metastatic liver disease is a life-limiting factor for patients with a variety of cancers. For unresectable liver metastases, the 5-year survival is < 5%.
- For selected histologies the 5-year survival of resectable hepatic metastases ranges from 20-60%, suggesting that control of liver metastases could result in prolonged survival.
- Phase I through III trials have shown that Hepatic Arterial Infusion (HAI) is safe. However, agents used thus far in HAI have limited efficacy.
- TKM-080301 is a lipid nanoparticle (LNP) formulation containing siRNA against the PLK1 (polo-like kinase-1) gene product. More specifically, TKM-080301 is a type of LNP formulation, referred to as SNALP (Stable Nucleic Acid Lipid Particles). PLK1 has been validated as a molecular target and a prognostic factor in a variety of cancers. Inhibition of PLK1 activity in proliferating cancer cells rapidly induces mitotic arrest and apoptosis.
- This study will offer HAI with TKM-080301 to patients with unresectable and/or life threatening primary liver cancer or liver metastases.
OBJECTIVES:
Primary Objective:
- To evaluate feasibility of administering TKM-080301 via HAI and to characterize the pharmacokinetics (PK) and pharmacodynamics of TKM-080301 administered by HAI.
Secondary Objectives:
- To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of TKM-080301.
- To evaluate response rate using RECIST, PET and EASL criteria.
- To evaluate the conversion rate from unresectable to resectable disease.
ELIGIBILITY:
- Patients with unresectable colorectal, pancreas, gastric, breast, ovarian and esophageal cancers with hepatic metastases; or primary liver cancer patients who have demonstrated progressive disease following standard of care treatment.
- 18 years old or greater with an ECOG 0-2
- Laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to surgery or chemotherapy.
DESIGN:
- This is a dose escalation phase-I study testing HAI of TKM-080301 for patients with unresectable colorectal, pancreas, gastric, breast, ovarian and esophageal cancers with hepatic metastases, or primary liver cancers.
- Up to 54 patients who meet eligibility criteria will receive HAI with TKM-080301.
- Initial dose will be 4 mg/m(2); treatment will be given every 2 weeks for up to 12 doses.
- Patients will be evaluated every 6 weeks. Patients whose tumors become resectable will be offered this option; patients who show progressive disease will be taken off treatment. All patients will be followed for survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TKM-080301 | Drug | – |
Primary outcome
To evaluate feasibility of administering TKM-080301 via HAI, and establish MTD and DLT.
Time frame: 2 years
3 secondary outcomes
Characterize PK & pharmacodynamics of TKM 080301
Time frame: 2 years
Eval biological effects of TKM-080301 on biopsies performed before & after 1 cycle of tx
Time frame: 2 years
To evaluate the potential conversion rate from unresectable to resectable disease.
Time frame: 2.5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2018.
- Background: PubMed 17291758Steegmaier 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.
- Background: PubMed 15173822Barr 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.
- Background: PubMed 16557283Strebhardt K, Ullrich A. Targeting polo-like kinase 1 for cancer therapy. Nat Rev Cancer. 2006 Apr;6(4):321-30. doi: 10.1038/nrc1841.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Udo Rudloff, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TKM-080301 in people with Colorectal Cancer With Hepatic Metastases and Pancreas Cancer With Hepatic Metastase, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate feasibility of administering TKM-080301 via HAI, and establish MTD and DLT. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01437007, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2018.