LymphomaPhase 1NCT01236586
RO4929097 in Children With Relapsed/Refractory Solid or CNS Tumors, Lymphoma, or T-Cell Leukemia
A Phase 1 study testing RO4929097 and Dexamethasone in people with Lymphoma and Brain Neoplasms, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
Background: The anti-cancer drug RO4929097 is being tested for its ability to block blood vessel growth to tumors and slow or stop the growth of cancer cells. However, it has been used in only a small number of adults and has not yet been tested in children. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Lymphoma, Brain Neoplasms, Sarcoma
- What is being tested?
- RO4929097 and Dexamethasone
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Oct 2010to 13 Apr 2011
- 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 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
- ELIGIBILITY CRITERIA:
- Patients greater than 12 months and less than or equal to 21 years of age with a diagnosis and histologic verification (except patients with intrinsic brain stem tumors, optic pathway gliomas) of measureable or evaluable relapsed or refractory disease. Current disease state must be one for which there is no known curative therapy, or therapy proven to prolong survival with an acceptable quality of life.
- Subjects must be able to swallow tablets.
- Patients who are pregnant, are known to be serologically positive for Hepatitis A, B, C, or have a history of liver disease, or have prolonged QTc are not eligible.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
St. Jude Childrens Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: A Phase 1/2 Study of RO4929097, An Oral Small Molecule Inhibitor of Gamma-Secretase, in Children With Relapsed/Refractory Solid or CNS Tumors, Lymphoma, or T-Cell Leukemia
Background:
- The anti-cancer drug RO4929097 is being tested for its ability to block blood vessel growth to tumors and slow or stop the growth of cancer cells. However, it has been used in only a small number of adults and has not yet been tested in children. Researchers are interested in determining whether RO4929097 is a safe and effective treatment for tumors or leukemia that has not responded to standard treatment.
Read more
Objectives:
- To determine the safety and effectiveness of RO4929097 as a treatment for children and adolescents who have been diagnosed with certain kinds of cancer that have not responded to standard treatment.
Eligibility:
- Children, adolescents, and young adults between 1 and 21 years of age who have been diagnosed with solid, nervous system, or blood-based cancers that have not responded to standard treatment.
Design:
- Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies. Some participants may also have a bone marrow biopsy to evaluate the state of their disease.
- Participants will be separated into three groups: One group will receive RO4929097 alone, and the other two will receive RO4929097 in combination with the immune-suppressing drug dexamethasone.
- RO4929097 will be given as tablets on one of two schedules: days 1 to 3 of every week (Schedule A) or days 1 to 5 of every week (Schedule B). The dosing schedule will be determined randomly. Every 4-week treatment period is one cycle, and participants may receive RO4929097 for up to 24 cycles.
- Participants will have frequent blood and urine tests and imaging studies to evaluate the progress of treatment, and will be asked to keep a diary to monitor any side effects.
Read the detailed description
Background:
- Notch signaling is aberrantly activated in a variety of human tumors including solid tumors and hematological malignancies including T-cell leukemia (T-ALL) and pediatric cancers, such as osteosarcoma, gliomas, medulloblastomas, ependymoma, and hematological malignancies.
- One emerging strategy to inhibit Notch signaling is the use of gamma-secretase inhibitors (GSIs), which prevent Notch receptor activation cleavage.
- RO4929097 is an orally administered small molecule that is a potent and selective GSI, which has shown antitumor activity in preclinical studies.
Objectives:
- To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose, and associated toxicities of RO4929097 administered orally to children with relapsed/refractory solid tumors or lymphoma on 2 schedules: once daily orally on a 3 day on/4 day off weekly schedule (schedule A) and once daily for 5 consecutive days weekly schedule (schedule B).
- To determine the MTD and recommended Phase 2 dose, and associated toxicities of RO4929097 administered with dexamethasone.
- To characterize the pharmacokinetics of RO4929097 in children with refractory cancer.
- To preliminarily define the anti-tumor activity of RO4929097 in children with refractory solid tumors within the confines of a phase I study.
- To determine initial efficacy on the anti-tumor activity of RO4929097 when combined with dexamethasone in children with relapsed/refractory T-ALL.
- To study the effects of RO4929097 on components of the Notch signaling pathway in peripheral blood mononuclear cells and/or T-ALL blasts, to examine archival tumor samples for expression or amplification of target molecules, and to preliminarily assess changes after treatment using FDG PET imaging.
Eligibility:
- Patients greater than 12 months and less than or equal to 21 years of age with a diagnosis and histologic verification (except patients with intrinsic brain stem tumors, optic pathway gliomas) of measureable or evaluable relapsed or refractory disease. Current disease state must be one for which there is no known curative therapy, or therapy proven to prolong survival with an acceptable quality of life.
- Subjects must be able to swallow tablets.
- Patients who are pregnant, are known to be serologically positive for Hepatitis A, B, C, or have a history of liver disease, or have prolonged QTc are not eligible.
Design:
- This phase I study will first evaluate the safety and pharmacokinetics of RO4929097 administered orally to children with relapsed/refractory solid tumors (Part 1) on 2 schedules: once daily on a 3 day on/4 day off weekly schedule (Schedule A) and once daily for 5 consecutive days weekly schedule (Schedule B).
- One cycle will be 28 days, and subjects may continue cycles in the absence of progressive disease or unacceptable treatment-related toxicity to a total of 24 cycles.
- After determining MTD of RO4929097, an evaluation of RO4929097 plus concomitant dexamethasone (Part 2) in at least one of the schedules tested in Part 1, will be undertaken.
- After the MTD of RO4929097 plus dexamethasone has been identified, enrollment of subjects with relapsed/refractory T-ALL (Part 3) will be undertaken to obtain initial efficacy data in this patient population.
- Conditions
- Lymphoma, Brain Neoplasms, Sarcoma, Osteosarcoma, Wilm's Tumor
- Being tested
- RO4929097, Dexamethasone
- Keywords
- Maximum Tolerated Dose, Toxicity, Pharmacokinetics, NOTCH Signaling Pathway, Expression of JAGGED 1 and 2, Cancer, Solid Tumor, Brain Tumor, Wilms Tumor, Osteosarcoma, Lymphoma
- Medical subject headings
- Lymphoma, Brain Neoplasms, Sarcoma, Osteosarcoma, Wilms Tumor, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO4929097Drug
DexamethasoneDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcomes of this study are self-reported fatigue, depression, and quality of life scores of patients before, at midpoint, and at completion of each cycle of their cancer treatment.
Secondary outcomes (1)
Cytokine profile
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2010 (estimated)
- Study start8 Oct 2010
- Primary completion13 Apr 2011
- Study completion13 Apr 2011
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 LymphomaStudies 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
- 0 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
- NCT01236586
- Sponsor's protocol ID
- 110017
- Other IDs
- 11-C-0017
- Status last verified
- 13 Apr 2011
- First submitted
- 5 Nov 2010
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999 Apr 30;284(5415):770-6. doi: 10.1126/science.284.5415.770.
PubMed 10221902Curry CL, Reed LL, Golde TE, Miele L, Nickoloff BJ, Foreman KE. Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi's sarcoma tumor cells. Oncogene. 2005 Sep 22;24(42):6333-44. doi: 10.1038/sj.onc.1208783.
PubMed 15940249Bray SJ. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006 Sep;7(9):678-89. doi: 10.1038/nrm2009.
PubMed 16921404
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
- A Phase 1/2 Study of RO4929097, An Oral Small Molecule Inhibitor of Gamma-Secretase, in Children With Relapsed/Refractory Solid or CNS Tumors, Lymphoma, or T-Cell Leukemia
- ClinicalTrials.gov ID
- NCT01236586
- Acronym / sponsor ID
- 110017
- Conditions
- Lymphoma, Brain Neoplasms, Sarcoma, Osteosarcoma, Wilm's Tumor
- Keywords
- Maximum Tolerated Dose, Toxicity, Pharmacokinetics, NOTCH Signaling Pathway, Expression of JAGGED 1 and 2, Cancer, Solid Tumor, Brain Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 8 Oct 2010
- Primary completion
- 13 Apr 2011 (actual)
- Study completion
- 13 Apr 2011 (actual)
- First posted
- 8 Nov 2010 (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:
- The anti-cancer drug RO4929097 is being tested for its ability to block blood vessel growth to tumors and slow or stop the growth of cancer cells. However, it has been used in only a small number of adults and has not yet been tested in children. Researchers are interested in determining whether RO4929097 is a safe and effective treatment for tumors or leukemia that has not responded to standard treatment.
Objectives:
- To determine the safety and effectiveness of RO4929097 as a treatment for children and adolescents who have been diagnosed with certain kinds of cancer that have not responded to standard treatment.
Eligibility:
- Children, adolescents, and young adults between 1 and 21 years of age who have been diagnosed with solid, nervous system, or blood-based cancers that have not responded to standard treatment.
Design:
- Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies. Some participants may also have a bone marrow biopsy to evaluate the state of their disease.
- Participants will be separated into three groups: One group will receive RO4929097 alone, and the other two will receive RO4929097 in combination with the immune-suppressing drug dexamethasone.
- RO4929097 will be given as tablets on one of two schedules: days 1 to 3 of every week (Schedule A) or days 1 to 5 of every week (Schedule B). The dosing schedule will be determined randomly. Every 4-week treatment period is one cycle, and participants may receive RO4929097 for up to 24 cycles.
- Participants will have frequent blood and urine tests and imaging studies to evaluate the progress of treatment, and will be asked to keep a diary to monitor any side effects.
Detailed description
Background:
- Notch signaling is aberrantly activated in a variety of human tumors including solid tumors and hematological malignancies including T-cell leukemia (T-ALL) and pediatric cancers, such as osteosarcoma, gliomas, medulloblastomas, ependymoma, and hematological malignancies.
- One emerging strategy to inhibit Notch signaling is the use of gamma-secretase inhibitors (GSIs), which prevent Notch receptor activation cleavage.
- RO4929097 is an orally administered small molecule that is a potent and selective GSI, which has shown antitumor activity in preclinical studies.
Objectives:
- To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose, and associated toxicities of RO4929097 administered orally to children with relapsed/refractory solid tumors or lymphoma on 2 schedules: once daily orally on a 3 day on/4 day off weekly schedule (schedule A) and once daily for 5 consecutive days weekly schedule (schedule B).
- To determine the MTD and recommended Phase 2 dose, and associated toxicities of RO4929097 administered with dexamethasone.
- To characterize the pharmacokinetics of RO4929097 in children with refractory cancer.
- To preliminarily define the anti-tumor activity of RO4929097 in children with refractory solid tumors within the confines of a phase I study.
- To determine initial efficacy on the anti-tumor activity of RO4929097 when combined with dexamethasone in children with relapsed/refractory T-ALL.
- To study the effects of RO4929097 on components of the Notch signaling pathway in peripheral blood mononuclear cells and/or T-ALL blasts, to examine archival tumor samples for expression or amplification of target molecules, and to preliminarily assess changes after treatment using FDG PET imaging.
Eligibility:
- Patients greater than 12 months and less than or equal to 21 years of age with a diagnosis and histologic verification (except patients with intrinsic brain stem tumors, optic pathway gliomas) of measureable or evaluable relapsed or refractory disease. Current disease state must be one for which there is no known curative therapy, or therapy proven to prolong survival with an acceptable quality of life.
- Subjects must be able to swallow tablets.
- Patients who are pregnant, are known to be serologically positive for Hepatitis A, B, C, or have a history of liver disease, or have prolonged QTc are not eligible.
Design:
- This phase I study will first evaluate the safety and pharmacokinetics of RO4929097 administered orally to children with relapsed/refractory solid tumors (Part 1) on 2 schedules: once daily on a 3 day on/4 day off weekly schedule (Schedule A) and once daily for 5 consecutive days weekly schedule (Schedule B).
- One cycle will be 28 days, and subjects may continue cycles in the absence of progressive disease or unacceptable treatment-related toxicity to a total of 24 cycles.
- After determining MTD of RO4929097, an evaluation of RO4929097 plus concomitant dexamethasone (Part 2) in at least one of the schedules tested in Part 1, will be undertaken.
- After the MTD of RO4929097 plus dexamethasone has been identified, enrollment of subjects with relapsed/refractory T-ALL (Part 3) will be undertaken to obtain initial efficacy data in this patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| RO4929097 | Drug | – |
| Dexamethasone | Drug | – |
Primary outcome
The primary outcomes of this study are self-reported fatigue, depression, and quality of life scores of patients before, at midpoint, and at completion of each cycle of their cancer treatment.
1 secondary outcome
Cytokine profile
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 10221902Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999 Apr 30;284(5415):770-6. doi: 10.1126/science.284.5415.770.
- Background: PubMed 15940249Curry CL, Reed LL, Golde TE, Miele L, Nickoloff BJ, Foreman KE. Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi's sarcoma tumor cells. Oncogene. 2005 Sep 22;24(42):6333-44. doi: 10.1038/sj.onc.1208783.
- Background: PubMed 16921404Bray SJ. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006 Sep;7(9):678-89. doi: 10.1038/nrm2009.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RO4929097 and Dexamethasone in people with Lymphoma and Brain Neoplasms, run by National Cancer Institute (NCI) at 2 sites 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?
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: withdrawn, 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 2 sites 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 was withdrawn before enrolling participants, so there are no results.
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?
The primary outcomes of this study are self-reported fatigue, depression, and quality of life scores of patients before, at midpoint, and at completion of each cycle of their cancer treatment.. 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 NCT01236586, 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.