Intraabdominal Cancers (Various Types)Phase 1NCT00283075
Mouse Cancer Cell-containing Macrobeads in the Treatment of Human Cancer
A Phase 1 study testing Cancer Macrobead placement in abdominal cavity in people with Intraabdominal Cancers (Various Types), run by The Rogosin Institute at 1 site in United States.
Trial summary
This is a phase 1 trial to evaluate the safety and toxicity of mouse kidney cancer cell-containing agarose-agarose macrobeads that are implanted in the abdominal cavity as a proposed biological treatment of patients with end-stage, treatment-resistant cancer. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Intraabdominal Cancers (Various Types)
- What is being tested?
- Cancer Macrobead placement in abdominal cavity
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Feb 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- End-stage, treatment resistant epithelial-derived cancer (carcinoma) arising originally within the abdominal cavity with expected minimum six-month survival
Who cannot join
- Multiple intraabdominal metastases or carcinomatosis or other medical conditions indicating that the procedure would be of too high a risk for the individual
Trial locations and contacts
1 site in 1 country.
United States1 site
NewYork Presbyterian Weill Cornell Medical Center
New York, New York, 10021
About this study
Official title: Use of Mouse Renal Adenocarcinoma Cell-containing Agarose-agarose Macrobeads in the Treatment of Patients With End-stage, Treatment-resistant Epithelial-derived Cancer
This is a phase 1 trial to evaluate the safety and toxicity of mouse kidney cancer cell-containing agarose-agarose macrobeads that are implanted in the abdominal cavity as a proposed biological treatment of patients with end-stage, treatment-resistant cancer. The macrobeads have been extensively tested in tumor models in mice and rats, as well as in forty-five veterinary patients (cats and dogs) with naturally occurring tumors of various types including breast cancer, prostate cancer, liver cancer, and lymphoma with clear tumor responses and no significant detectable toxicity.
Read the detailed description
Cancer in its various forms continues to be a major U.S. health problem, accounting for 550,000 deaths a year, as well as much disability and suffering. Treatment for cancer has traditionally consisted of three modalities: surgery, radiation therapy, and chemotherapy. Advances with all three modalities over the years have produced long-term remissions and/or cures in certain types of cancer such as the leukemias, and prolonged survival for many other patients. Much remains to be accomplished, however, especially with respect to the treatment of solid tumors, including some of the most common cancers such as those of the lung, colon, breast, ovary, prostate and kidney. New types of less toxic and debilitating therapy are needed.
Among the therapeutic possibilities currently being explored, those that involve biological control mechanisms seem both promising and attractive. Although it has long been thought that cancer cells are not subject to the same regulatory growth control mechanisms that function in normal cells, there is a substantial body of evidence that they can respond to feedback signals telling them to slow or stop their growth. In addition, it has been determined that a relatively small population of cells within a tumor (cancer "stem" or progenitor cells) are responsible for continued tumor growth and that it is these cells that must be controlled if biological anti-tumor therapy is to be effective.
The proposed cancer treatment being tested in this Phase 1 clinical trial is based on the concept that tumor growth can be controlled by tumor mass or signals that indicate that such mass is present. In this case, however, the induction of the growth-slowing signals is brought about not by tumor mass, but by placing mouse kidney cancer cells in an agarose matrix, which both selects for cancer progenitor cells and also causes them to produce and release signals that inhibit the growth of freely growing cancer cells of the same or different type in a laboratory dish or in a tumor-bearing animal or human (i.e. is also not species-specific). This approach has proven both safe and effective in animal models and veterinary patients, and it is now in the first stage of human testing. With Phase 1 completed, we are now implementing Phase 2 efficacy trials that for the present are focused on colorectal cancer, pancreatic cancer, and prostate cancer. The Phase 1 trial remains open to a range of epithelial-derived cancer.
- Conditions
- Intraabdominal Cancers (Various Types)
- Being tested
- Cancer Macrobead placement in abdominal cavity
- Keywords
- intraabdominal cancer (carcinomas), agarose macrobeads, mouse kidney cancer cells, cancer cell growth inhibition
- Medical subject headings
- Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cancer Macrobead placement in abdominal cavityBiological
Also called cancer macrobead
8 macrobeads per kg
| Study group | Role | What they receive |
|---|---|---|
| Cancer macrobeads | Experimental | Cancer Macrobead placement in abdominal cavity Receives: Biological: Cancer Macrobead placement in abdominal cavity |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of RENCA Macrobeads
Dose limiting toxicity (DLT) was defined as:
- any Grade 2 allergic reaction of generalized urticaria or any other Grade ≥ 3 allergic reaction;
- any Grade ≥ 3 infection and
- any Grade ≥ 3 local (intraperitoneal) reaction and any Grade ≥ 3 hematologic or non- hematologic reaction.
This definition of DLT is in accord with the NCI CTCAE v3.0.
Maximum tolerated dose (MTD) was to be identified if, within a cohort, > 1 subject out of the first 3, or 2 subjects out of 5 experienced DLT. In such a case, the MTD will have been exceeded, and the administration of the study agent was to cease. MTD would not be considered to have been reached if no DLTs were observed.
Measured: 6 months
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Dose limiting toxicity (DLT) was defined as:
- any Grade 2 allergic reaction of generalized urticaria or any other Grade ≥ 3 allergic reaction;
- any Grade ≥ 3 infection and
- any Grade ≥ 3 local (intraperitoneal) reaction and any Grade ≥ 3 hematologic or non- hematologic reaction.
This definition of DLT is in accord with the NCI CTCAE v3.0.
Measured: 6 months
Secondary outcomes (1)
Overall Survival
Overall Survival (OS) was measured as date of first implantation to date of death of any cause, and was analyzed using the Kaplan-Meier method.
Measured: From date of RENCA macrobeads implantation until date of death from any cause
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2006 (estimated)
- Study startJan 2005
- Primary completionDec 2012
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Intraabdominal Cancers (Various Types)Studies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Rogosin Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Barry H Smith, MD, PhD, Principal investigator, The Rogosin Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00283075
- Sponsor's protocol ID
- 0407007343
- Status last verified
- Jan 2019
- First submitted
- 26 Jan 2006
- Last updated
- 16 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
DeWys WD. Studies correlating the growth rate of a tumor and its metastases and providing evidence for tumor-related systemic growth-retarding factors. Cancer Res. 1972 Feb;32(2):374-9. No abstract available.
PubMed 4258017Fisher B, Gunduz N, Coyle J, Rudock C, Saffer E. Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res. 1989 Apr 15;49(8):1996-2001.
PubMed 2702641Prehn RT. The inhibition of tumor growth by tumor mass. Cancer Res. 1991 Jan 1;51(1):2-4.
PubMed 1988084Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001 Nov 1;414(6859):105-11. doi: 10.1038/35102167.
PubMed 11689955Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8. doi: 10.1073/pnas.0530291100. Epub 2003 Mar 10.
PubMed 12629218Smith BH, Gazda LS, Conn BL, Jain K, Asina S, Levine DM, Parker TS, Laramore MA, Martis PC, Vinerean HV, David EM, Qiu S, North AJ, Couto CG, Post GS, Waters DJ, Cordon-Cardo C, Hall RD, Gordon BR, Diehl CH, Stenzel KH, Rubin AL. Hydrophilic agarose macrobead cultures select for outgrowth of carcinoma cell populations that can restrict tumor growth. Cancer Res. 2011 Feb 1;71(3):725-35. doi: 10.1158/0008-5472.CAN-10-2258. Epub 2011 Jan 24.
PubMed 21266362Smith BH, Gazda LS, Conn BL, Jain K, Asina S, Levine DM, Parker TS, Laramore MA, Martis PC, Vinerean HV, David EM, Qiu S, Cordon-Cardo C, Hall RD, Gordon BR, Diehl CH, Stenzel KH, Rubin AL. Three-dimensional culture of mouse renal carcinoma cells in agarose macrobeads selects for a subpopulation of cells with cancer stem cell or cancer progenitor properties. Cancer Res. 2011 Feb 1;71(3):716-24. doi: 10.1158/0008-5472.CAN-10-2254. Epub 2011 Jan 24.
PubMed 21266363Gazda LS, Martis PC, Laramore MA, Bautista MA, Dudley A, Vinerean HV, Smith BH. Treatment of agarose-agarose RENCA macrobeads with docetaxel selects for OCT4(+) cells with tumor-initiating capability. Cancer Biol Ther. 2013 Dec;14(12):1147-57. doi: 10.4161/cbt.26455. Epub 2013 Sep 12.
PubMed 24025409
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Mouse Renal Adenocarcinoma Cell-containing Agarose-agarose Macrobeads in the Treatment of Patients With End-stage, Treatment-resistant Epithelial-derived Cancer
- ClinicalTrials.gov ID
- NCT00283075
- Acronym / sponsor ID
- 0407007343
- Conditions
- Intraabdominal Cancers (Various Types)
- Keywords
- intraabdominal cancer (carcinomas), agarose macrobeads, mouse kidney cancer cells, cancer cell growth inhibition
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- The Rogosin InstituteUniversity, hospital or other
- Study start
- Jan 2005
- Primary completion
- Dec 2012 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 27 Jan 2006 (estimated)
- Results
- Posted 10 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1 trial to evaluate the safety and toxicity of mouse kidney cancer cell-containing agarose-agarose macrobeads that are implanted in the abdominal cavity as a proposed biological treatment of patients with end-stage, treatment-resistant cancer. The macrobeads have been extensively tested in tumor models in mice and rats, as well as in forty-five veterinary patients (cats and dogs) with naturally occurring tumors of various types including breast cancer, prostate cancer, liver cancer, and lymphoma with clear tumor responses and no significant detectable toxicity.
Detailed description
Cancer in its various forms continues to be a major U.S. health problem, accounting for 550,000 deaths a year, as well as much disability and suffering. Treatment for cancer has traditionally consisted of three modalities: surgery, radiation therapy, and chemotherapy. Advances with all three modalities over the years have produced long-term remissions and/or cures in certain types of cancer such as the leukemias, and prolonged survival for many other patients. Much remains to be accomplished, however, especially with respect to the treatment of solid tumors, including some of the most common cancers such as those of the lung, colon, breast, ovary, prostate and kidney. New types of less toxic and debilitating therapy are needed.
Among the therapeutic possibilities currently being explored, those that involve biological control mechanisms seem both promising and attractive. Although it has long been thought that cancer cells are not subject to the same regulatory growth control mechanisms that function in normal cells, there is a substantial body of evidence that they can respond to feedback signals telling them to slow or stop their growth. In addition, it has been determined that a relatively small population of cells within a tumor (cancer "stem" or progenitor cells) are responsible for continued tumor growth and that it is these cells that must be controlled if biological anti-tumor therapy is to be effective.
The proposed cancer treatment being tested in this Phase 1 clinical trial is based on the concept that tumor growth can be controlled by tumor mass or signals that indicate that such mass is present. In this case, however, the induction of the growth-slowing signals is brought about not by tumor mass, but by placing mouse kidney cancer cells in an agarose matrix, which both selects for cancer progenitor cells and also causes them to produce and release signals that inhibit the growth of freely growing cancer cells of the same or different type in a laboratory dish or in a tumor-bearing animal or human (i.e. is also not species-specific). This approach has proven both safe and effective in animal models and veterinary patients, and it is now in the first stage of human testing. With Phase 1 completed, we are now implementing Phase 2 efficacy trials that for the present are focused on colorectal cancer, pancreatic cancer, and prostate cancer. The Phase 1 trial remains open to a range of epithelial-derived cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cancer macrobeads | Experimental | Biological: Cancer Macrobead placement in abdominal cavityCancer Macrobead placement in abdominal cavity |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- End-stage, treatment resistant epithelial-derived cancer (carcinoma) arising originally within the abdominal cavity with expected minimum six-month survival
Key exclusion criteria (1 listed)
- Multiple intraabdominal metastases or carcinomatosis or other medical conditions indicating that the procedure would be of too high a risk for the individual
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 |
|---|---|---|
| Cancer Macrobead placement in abdominal cavityAlso: cancer macrobead8 macrobeads per kg | Biological | Cancer macrobeads |
Primary outcome
Maximum Tolerated Dose (MTD) of RENCA Macrobeads
Time frame: 6 months
Dose limiting toxicity (DLT) was defined as: * any Grade 2 allergic reaction of generalized urticaria or any other Grade ≥ 3 allergic reaction; * any Grade ≥ 3 infection and * any Grade ≥ 3 local (intraperitoneal) reaction and any Grade ≥ 3 hematologic or non- hematologic reaction. This definition of DLT is in accord with the NCI CTCAE v3.0. Maximum tolerated dose (MTD) was to be identified if, within a cohort, > 1 subject out of the first 3, or 2 subjects out of 5 experienced DLT. In such a case, the MTD will have been exceeded, and the administration of the study agent was to cease. MTD would not be considered to have been reached if no DLTs were observed.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time frame: 6 months
Dose limiting toxicity (DLT) was defined as: * any Grade 2 allergic reaction of generalized urticaria or any other Grade ≥ 3 allergic reaction; * any Grade ≥ 3 infection and * any Grade ≥ 3 local (intraperitoneal) reaction and any Grade ≥ 3 hematologic or non- hematologic reaction. This definition of DLT is in accord with the NCI CTCAE v3.0.
1 secondary outcome
Overall Survival
Time frame: From date of RENCA macrobeads implantation until date of death from any cause
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 4258017DeWys WD. Studies correlating the growth rate of a tumor and its metastases and providing evidence for tumor-related systemic growth-retarding factors. Cancer Res. 1972 Feb;32(2):374-9. No abstract available.
- Background: PubMed 2702641Fisher B, Gunduz N, Coyle J, Rudock C, Saffer E. Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res. 1989 Apr 15;49(8):1996-2001.
- Background: PubMed 1988084Prehn RT. The inhibition of tumor growth by tumor mass. Cancer Res. 1991 Jan 1;51(1):2-4.
- Background: PubMed 11689955Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001 Nov 1;414(6859):105-11. doi: 10.1038/35102167.
- Background: PubMed 12629218Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8. doi: 10.1073/pnas.0530291100. Epub 2003 Mar 10.
- Background: PubMed 21266362Smith BH, Gazda LS, Conn BL, Jain K, Asina S, Levine DM, Parker TS, Laramore MA, Martis PC, Vinerean HV, David EM, Qiu S, North AJ, Couto CG, Post GS, Waters DJ, Cordon-Cardo C, Hall RD, Gordon BR, Diehl CH, Stenzel KH, Rubin AL. Hydrophilic agarose macrobead cultures select for outgrowth of carcinoma cell populations that can restrict tumor growth. Cancer Res. 2011 Feb 1;71(3):725-35. doi: 10.1158/0008-5472.CAN-10-2258. Epub 2011 Jan 24.
- Background: PubMed 21266363Smith BH, Gazda LS, Conn BL, Jain K, Asina S, Levine DM, Parker TS, Laramore MA, Martis PC, Vinerean HV, David EM, Qiu S, Cordon-Cardo C, Hall RD, Gordon BR, Diehl CH, Stenzel KH, Rubin AL. Three-dimensional culture of mouse renal carcinoma cells in agarose macrobeads selects for a subpopulation of cells with cancer stem cell or cancer progenitor properties. Cancer Res. 2011 Feb 1;71(3):716-24. doi: 10.1158/0008-5472.CAN-10-2254. Epub 2011 Jan 24.
- Background: PubMed 24025409Gazda LS, Martis PC, Laramore MA, Bautista MA, Dudley A, Vinerean HV, Smith BH. Treatment of agarose-agarose RENCA macrobeads with docetaxel selects for OCT4(+) cells with tumor-initiating capability. Cancer Biol Ther. 2013 Dec;14(12):1147-57. doi: 10.4161/cbt.26455. Epub 2013 Sep 12.
- Individual participant dataSharing planned: No
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.
Barry H Smith, MD, PhD principal investigator
The Rogosin Institute
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 Cancer Macrobead placement in abdominal cavity in people with Intraabdominal Cancers (Various Types), run by The Rogosin Institute 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 1 inclusion and 1 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 16 Jan 2019. 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?
Yes. Results are posted in the registry (first posted 10 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) of RENCA Macrobeads (time frame: 6 months). The study lists 2 primary outcomes in all. 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 NCT00283075, which also lists 8 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 16 Jan 2019.