Solid TumorsPhase 1NCT00322140
CDDO to Treat Solid Tumors and Lymphomas
A Phase 1 study testing CDDO in people with Solid Tumors and Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: CDDO is a novel synthetic triterpenoid which is a potent multifunctional molecule. It induces apoptosis in vitro in malignant cells through both intrinsic and extrinsic pathways, and it controls cellular differentiation, apoptosis, and growth inhibition by serving as a ligand for the transcription factor… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Lymphoma
- What is being tested?
- CDDO
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2006to 14 Jan 2008
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed (by NIH pathology department) solid tumor malignancy or lymphoma that is metastatic or unresectable and for which there is not therapy with survival benefit and standard curative or palliative measures do not exist.
- Patients must have measurable or evaluable disease.
- Patients must have recovered less than or equal to grade 1 toxicity levels due to adverse events and/or toxicity of prior chemotherapy or biologic therapy. They must not have had chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C, 8 weeks for UCN-01). Patients must be at least 1 month since any prior radiation or major surgery. Patients must be greater than or equal to 2 weeks since any prior participation in a Phase Zero study. Patients on bisphosphonates for any cancer or on androgen deprivation therapy for prostate cancer, however, will not need to discontinue this therapy in order to be eligible.
- Age greater than or equal to 18 years.
- ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%, see Appendix A).
- Life expectancy of greater than 3 months.
Show all 17Show fewer
- Patients must have normal or adequate organ and marrow function as defined below:
- Hb greater than or equal to 10 g/dL
- absolute neutrophil count greater than or equal to 1,500/ L
- platelets greater than or equal to 100,000/ L
- total bilirubin less than or equal to 1.5 normal institutional limits
- AST (SGOT)/ALT (SGPT) less than or equal to 2.5 x institutional upper limit of normal
- creatinine clearance less than 1 x upper limit of normal
- OR
- -creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
- The effects of CDDO on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation and for 2 months after discontinuation of the study. Women of child bearing potential must have a negative pregnancy test in order to be eligible. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CDDO, breastfeeding should be discontinued if the mother is treated with CDDO.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients receiving any other investigational agents.
- Patients with known brain metastases are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for at least 6 months after treatment of the brain metastases without steroids or anti-seizure medications. These patients may be enrolled at the discretion of the principal investigator.
- History of allergic reactions attributed to other synthetic triperinoids or compounds of similar chemical or biologic composition to CDDO, such as derivative compounds 1-[2-cyano-3-,12- dioxooleana -1,9-dien-28-oyl] imidazole (CDDO-Im), and C-28 methyl ester of 2-cyano-3,12-dioxoolen-1,9-dien-28-oic acid (CDDO-Me).
- Patients with clinically significant illnesses which could compromise participation in the study, including, but not limited to: Active or uncontrolled infection, immune deficiencies or confirmed diagnosis of HIV infection, Hepatitis B, Hepatitis C, or uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past six months, uncontrolled cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements.
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: Phase I Study of CDDO in Solid Tumors and Lymphomas
Background:
- CDDO is a novel synthetic triterpenoid which is a potent multifunctional molecule. It induces apoptosis in vitro in malignant cells through both intrinsic and extrinsic pathways, and it controls cellular differentiation, apoptosis, and growth inhibition by serving as a ligand for the transcription factor peroxisome proliferator activator receptor-gamma (PPAR gamma).
- Based on in vitro activity, it holds considerable promise as a novel anti-tumor agent against a wide range of malignancies by concurrently targeting multiple pathways leading to oncogenesis.
- In vivo data demonstrates that the drug is well tolerated in dogs, and has anti-tumor effects, dependent upon dose schedule.
Read more
Objectives:
Primary:
- To determine the dose limiting toxicities, toxicity profile, and maximum tolerated dose of CDDO when administered in adult patients with solid tumors and lymphomas.
- To characterize the pharmacokinetics of CDDO.
Secondary:
- To obtain preliminary evidence of anti-tumor activity of CDDO in this population.
- To evaluate the in vivo molecular and biological effects of CDDO by assessing changes in biomarkers of apoptosis and cell cycle arrest.
Eligibility:
- Patients with advance, histological-confirmed malignancies refractory to standard therapy or for which no standard therapy exist.
- Patients should have adequate liver, renal and bone marrow function.
Study Design:
- Accordingly with the accelerated titration design 4B, dose levels will initially be increased at 100% increments, and one new patient per dose level will be treated per 4-week course.
- The accelerated phase ends when one patient experiences DLT during any course of treatment or when two different patients experience grade 2 toxicity during first course of treatment.
- When the first instance of grade 2 toxicity is observed two additional patients must have been treated at that dose, or a higher dose, (during any course) without experiencing moderate or worse toxicity, in order that the accelerated phase continue.
- When the accelerated phase ends, dose-escalation will revert to a more conservative modified Fibonacci scheme with 40% dose-step increments, with at least 3 patients treated per dose level.
Read the detailed description
Background:
- CDDO is a novel synthetic triterpenoid which is a potent multifunctional molecule. It induces apoptosis in vitro in malignant cells through both intrinsic and extrinsic pathways, and it controls cellular differentiation, apoptosis, and growth inhibition by serving as a ligand for the transcription factor peroxisome proliferator activator receptor-gamma (PPAR gamma).
- Based on in vitro activity, it holds considerable promise as a novel anti-tumor agent against a wide range of malignancies by concurrently targeting multiple pathways leading to oncogenesis.
- In vivo data demonstrates that the drug is well tolerated in dogs, and has anti-tumor effects, dependent upon dose schedule.
Objectives:
Primary:
- To determine the dose limiting toxicities, toxicity profile, and maximum tolerated dose of CDDO when administered in adult patients with solid tumors and lymphomas.
- To characterize the pharmacokinetics of CDDO.
Secondary:
- To obtain preliminary evidence of anti-tumor activity of CDDO in this population.
- To evaluate the in vivo molecular and biological effects of CDDO by assessing changes in biomarkers of apoptosis and cell cycle arrest.
Eligibility:
- Patients with advance, histological-confirmed malignancies refractory to standard therapy or for which no standard therapy exist.
- Patients should have adequate liver, renal and bone marrow function.
Study Design:
- Accordingly with the accelerated titration design 4B, dose levels will initially be increased at 100% increments, and one new patient per dose level will be treated per 4-week course.
- The accelerated phase ends when one patient experiences DLT during any course of treatment or when two different patients experience grade 2 toxicity during first course of treatment.
- When the first instance of grade 2 toxicity is observed two additional patients must have been treated at that dose, or a higher dose, (during any course) without experiencing moderate or worse toxicity, in order that the accelerated phase continue.
- When the accelerated phase ends, dose-escalation will revert to a more conservative modified Fibonacci scheme with 40% dose-step increments, with at least 3 patients treated per dose level.
- Conditions
- Solid Tumors, Lymphoma
- Being tested
- CDDO
- Keywords
- Metastatic, Triterpenoids, 2-Cyano-3,12-Dioxooleana-1,9(11)Dien-28oic Acid, Dose-Limiting, Pharmacokinetic, Solid Tumor, Lymphoma
- Medical subject headings
- Lymphoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CDDODrug
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the dose limiting toxicities, toxicity profile, and maximum tolerated dose of CDDO when administered in adult patients with solid tumors and lymphomas.
Secondary outcomes (1)
To obtain preliminary evidence of anti-tumor activity of CDDO in this population.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2006 (estimated)
- Study start1 May 2006
- Primary completion14 Jan 2008
- Study completion14 Jan 2008
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 Solid TumorsStudies 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
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00322140
- Sponsor's protocol ID
- 060151
- Other IDs
- 06-C-0151
- Status last verified
- 25 Aug 2011
- First submitted
- 4 May 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Ito Y, Pandey P, Sporn MB, Datta R, Kharbanda S, Kufe D. The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism. Mol Pharmacol. 2001 May;59(5):1094-9. doi: 10.1124/mol.59.5.1094.
PubMed 11306692Lapillonne H, Konopleva M, Tsao T, Gold D, McQueen T, Sutherland RL, Madden T, Andreeff M. Activation of peroxisome proliferator-activated receptor gamma by a novel synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest and apoptosis in breast cancer cells. Cancer Res. 2003 Sep 15;63(18):5926-39.
PubMed 14522919Ito Y, Pandey P, Place A, Sporn MB, Gribble GW, Honda T, Kharbanda S, Kufe D. The novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism. Cell Growth Differ. 2000 May;11(5):261-7.
PubMed 10845427
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of CDDO in Solid Tumors and Lymphomas
- ClinicalTrials.gov ID
- NCT00322140
- Acronym / sponsor ID
- 060151
- Conditions
- Solid Tumors, Lymphoma
- Keywords
- Metastatic, Triterpenoids, 2-Cyano-3,12-Dioxooleana-1,9(11)Dien-28oic Acid, Dose-Limiting, Pharmacokinetic, Solid Tumor, Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 1 May 2006
- Primary completion
- 14 Jan 2008 (actual)
- Study completion
- 14 Jan 2008 (actual)
- First posted
- 5 May 2006 (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:
- CDDO is a novel synthetic triterpenoid which is a potent multifunctional molecule. It induces apoptosis in vitro in malignant cells through both intrinsic and extrinsic pathways, and it controls cellular differentiation, apoptosis, and growth inhibition by serving as a ligand for the transcription factor peroxisome proliferator activator receptor-gamma (PPAR gamma).
- Based on in vitro activity, it holds considerable promise as a novel anti-tumor agent against a wide range of malignancies by concurrently targeting multiple pathways leading to oncogenesis.
- In vivo data demonstrates that the drug is well tolerated in dogs, and has anti-tumor effects, dependent upon dose schedule.
Objectives:
Primary:
- To determine the dose limiting toxicities, toxicity profile, and maximum tolerated dose of CDDO when administered in adult patients with solid tumors and lymphomas.
- To characterize the pharmacokinetics of CDDO.
Secondary:
- To obtain preliminary evidence of anti-tumor activity of CDDO in this population.
- To evaluate the in vivo molecular and biological effects of CDDO by assessing changes in biomarkers of apoptosis and cell cycle arrest.
Eligibility:
- Patients with advance, histological-confirmed malignancies refractory to standard therapy or for which no standard therapy exist.
- Patients should have adequate liver, renal and bone marrow function.
Study Design:
- Accordingly with the accelerated titration design 4B, dose levels will initially be increased at 100% increments, and one new patient per dose level will be treated per 4-week course.
- The accelerated phase ends when one patient experiences DLT during any course of treatment or when two different patients experience grade 2 toxicity during first course of treatment.
- When the first instance of grade 2 toxicity is observed two additional patients must have been treated at that dose, or a higher dose, (during any course) without experiencing moderate or worse toxicity, in order that the accelerated phase continue.
- When the accelerated phase ends, dose-escalation will revert to a more conservative modified Fibonacci scheme with 40% dose-step increments, with at least 3 patients treated per dose level.
Detailed description
Background:
- CDDO is a novel synthetic triterpenoid which is a potent multifunctional molecule. It induces apoptosis in vitro in malignant cells through both intrinsic and extrinsic pathways, and it controls cellular differentiation, apoptosis, and growth inhibition by serving as a ligand for the transcription factor peroxisome proliferator activator receptor-gamma (PPAR gamma).
- Based on in vitro activity, it holds considerable promise as a novel anti-tumor agent against a wide range of malignancies by concurrently targeting multiple pathways leading to oncogenesis.
- In vivo data demonstrates that the drug is well tolerated in dogs, and has anti-tumor effects, dependent upon dose schedule.
Objectives:
Primary:
- To determine the dose limiting toxicities, toxicity profile, and maximum tolerated dose of CDDO when administered in adult patients with solid tumors and lymphomas.
- To characterize the pharmacokinetics of CDDO.
Secondary:
- To obtain preliminary evidence of anti-tumor activity of CDDO in this population.
- To evaluate the in vivo molecular and biological effects of CDDO by assessing changes in biomarkers of apoptosis and cell cycle arrest.
Eligibility:
- Patients with advance, histological-confirmed malignancies refractory to standard therapy or for which no standard therapy exist.
- Patients should have adequate liver, renal and bone marrow function.
Study Design:
- Accordingly with the accelerated titration design 4B, dose levels will initially be increased at 100% increments, and one new patient per dose level will be treated per 4-week course.
- The accelerated phase ends when one patient experiences DLT during any course of treatment or when two different patients experience grade 2 toxicity during first course of treatment.
- When the first instance of grade 2 toxicity is observed two additional patients must have been treated at that dose, or a higher dose, (during any course) without experiencing moderate or worse toxicity, in order that the accelerated phase continue.
- When the accelerated phase ends, dose-escalation will revert to a more conservative modified Fibonacci scheme with 40% dose-step increments, with at least 3 patients treated per dose level.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients must have histologically confirmed (by NIH pathology department) solid tumor malignancy or lymphoma that is metastatic or unresectable and for which there is not therapy with survival benefit and standard curative or palliative measures do not exist.
- Patients must have measurable or evaluable disease.
- Patients must have recovered less than or equal to grade 1 toxicity levels due to adverse events and/or toxicity of prior chemotherapy or biologic therapy. They must not have had chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C, 8 weeks for UCN-01). Patients must be at least 1 month since any prior radiation or major surgery. Patients must be greater than or equal to 2 weeks since any prior participation in a Phase Zero study. Patients on bisphosphonates for any cancer or on androgen deprivation therapy for prostate cancer, however, will not need to discontinue this therapy in order to be eligible.
- Age greater than or equal to 18 years.
- ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%, see Appendix A).
Key exclusion criteria (4 listed)
- Patients receiving any other investigational agents.
- Patients with known brain metastases are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for at least 6 months after treatment of the brain metastases without steroids or anti-seizure medications. These patients may be enrolled at the discretion of the principal investigator.
- History of allergic reactions attributed to other synthetic triperinoids or compounds of similar chemical or biologic composition to CDDO, such as derivative compounds 1-[2-cyano-3-,12- dioxooleana -1,9-dien-28-oyl] imidazole (CDDO-Im), and C-28 methyl ester of 2-cyano-3,12-dioxoolen-1,9-dien-28-oic acid (CDDO-Me).
- Patients with clinically significant illnesses which could compromise participation in the study, including, but not limited to: Active or uncontrolled infection, immune deficiencies or confirmed diagnosis of HIV infection, Hepatitis B, Hepatitis C, or uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past six months, uncontrolled cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements.
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 |
|---|---|---|
| CDDO | Drug | – |
Primary outcome
To determine the dose limiting toxicities, toxicity profile, and maximum tolerated dose of CDDO when administered in adult patients with solid tumors and lymphomas.
1 secondary outcome
To obtain preliminary evidence of anti-tumor activity of CDDO in this population.
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 2 Jul 2017.
- Background: PubMed 11306692Ito Y, Pandey P, Sporn MB, Datta R, Kharbanda S, Kufe D. The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism. Mol Pharmacol. 2001 May;59(5):1094-9. doi: 10.1124/mol.59.5.1094.
- Background: PubMed 14522919Lapillonne H, Konopleva M, Tsao T, Gold D, McQueen T, Sutherland RL, Madden T, Andreeff M. Activation of peroxisome proliferator-activated receptor gamma by a novel synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest and apoptosis in breast cancer cells. Cancer Res. 2003 Sep 15;63(18):5926-39.
- Background: PubMed 10845427Ito Y, Pandey P, Place A, Sporn MB, Gribble GW, Honda T, Kharbanda S, Kufe D. The novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism. Cell Growth Differ. 2000 May;11(5):261-7.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 CDDO in people with Solid Tumors and Lymphoma, 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 17 inclusion and 4 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 2 Jul 2017. 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 determine the dose limiting toxicities, toxicity profile, and maximum tolerated dose of CDDO when administered in adult patients with solid tumors and lymphomas.. 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 NCT00322140, 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 2 Jul 2017.