LymphomaPhase 1NCT00005639
Azacitidine Plus Phenylbutyrate in Treating Patients With Advanced or Metastatic Solid Tumors That Have Not Responded to Previous Treatment
A Phase 1 study testing Azacitidine Injection and sodium phenylbutyrate in people with Lymphoma and Small Intestine Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of azacitidine plus phenylbutyrate in treating patients with advanced or… Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Lymphoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- Azacitidine Injection and sodium phenylbutyrate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2000to Jul 2005
- 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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor not amenable to curative therapy
- Lymphoma allowed
- Progressive disease
- Evaluable disease
- No CNS metastases by CT scan or MRI
Show all 39Show fewer
- PATIENT CHARACTERISTICS:
- Age:
- 18 and over
- Performance status:
- ECOG 0-2
- Life expectancy:
- Not specified
- Hematopoietic:
- Hemoglobin at least 8 g/dL (may be achieved by transfusion)
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hepatic:
- Bilirubin no greater than 2 mg/dL (unless due to hemolysis or Gilbert's syndrome)
- SGOT and SGPT less than 2 times upper limit of normal
- Renal:
- Creatinine no greater than 2.0 mg/dL
- Other:
- No active infection
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception for 2 weeks before, during, and 3 months after study participation
- PRIOR CONCURRENT THERAPY:
- Biologic therapy:
- Not specified
- Chemotherapy:
- At least 4 weeks since prior adjuvant chemotherapy for advanced or metastatic disease and recovered
- Endocrine therapy:
- Not specified
- Radiotherapy:
- At least 4 weeks since prior radiotherapy and recovered
- Surgery:
- Not specified
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
About this study
Official title: A Phase I Dose Escalation to Maximally Tolerated Dose Trial of 5-Azacytidine (5 AC, NSC 102816) in Combination With Sodium Phenylbutyrate (PB, NSC 657802) in Patients With Refractory Solid Tumors
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of azacitidine plus phenylbutyrate in treating patients with advanced or metastatic solid tumors that have not responded to previous treatment.
Read the detailed description
OBJECTIVES:
- Evaluate the safety and toxicity of azacitidine plus phenylbutyrate in patients with refractory solid tumors.
- Determine the maximum tolerated dose of this treatment regimen where maximal gene reexpression occurs in these patients.
- Evaluate the pharmacokinetics of these drugs in these patients.
- Determine the minimally effective dose of azacitidine in combination with phenylbutyrate that elicits a biological or clinical response in these patients.
OUTLINE: This is a dose escalation study.
Patients receive azacitidine subcutaneously for 14-21 days and sodium phenylbutyrate IV continuously for 1-7 days. Treatment repeats every 35 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses and durations of treatment with azacitidine and phenylbutyrate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.
PROJECTED ACCRUAL: Approximately 3-50 patients will be accrued for this study within 12-18 months.
- Being tested
- Azacitidine Injection, sodium phenylbutyrate
- Keywords
- stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, small intestine lymphoma, unspecified adult solid tumor, protocol specific, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III adult Burkitt lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma
- Medical subject headings
- Lymphoma, Hodgkin Disease, Lymphoma, T-Cell, Cutaneous, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azacitidine InjectionDrug
Also called AC, 5-AC
subcutaneous injection (SC)
sodium phenylbutyrateDrug
continuous intravenous (CIV)
| Study group | Role | What they receive |
|---|---|---|
| Regimen A: 14-day 5-AC with intermittent phenylbutyrate | Experimental | Participants receive low-dose regimen of 5-AC with intermittent phenylbutyrate 400 mg/m2/day by continuous intravenous (CIV) over 24 hours on Days 6 and 13. Each cycle lasts 35 days.
Cohort A1: 25 mg/m2/day subcutaneous (SC) Cohort A-1: 18.75 mg/m2/day SC Cohort A-2: 15 mg/m2/day SC Cohort A-3: 10 mg/m2/day SC Receives: Drug: Azacitidine Injection; Drug: sodium phenylbutyrate |
| Regimen B: 7-day 5-AC with sequential phenylbutyrate | Experimental | Participants receive 5-AC 75mg/m2/day SC for 7 days, followed sequentially by two different doses of phenylbutyrate CIV starting on Day 8 and continuing for 7 days. Each cycle lasts 35 days
Cohort B1: Phenylbutyrate 200 mg/m2/day CIV Cohort B2: Phenylbutyrate 400 mg/m2/day CIV Receives: Drug: Azacitidine Injection; Drug: sodium phenylbutyrate |
| Regimen C: 21-day 5-AC with weekly phenylbutyrate | Experimental | Participants receive two different daily doses of 5-AC SC for 21 days and phenylbutyrate 400 mg/m2/day CIV over 24 hours once-per-week. Each cycle lasts 42 days.
Cohort C1: 5-AC 10mg/m2/day SC Cohort C2: 5-AC 12.5mg/m2/day SC Receives: Drug: Azacitidine Injection; Drug: sodium phenylbutyrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minimal Effective Dose (MED) of Azacitidine with Phenylbutyrate
MED (milligrams) of combined Azacitidine and Phenylbutyrate that results in clinical response, as defined by Standard World Health Organization (WHO) criteria and/or target inhibition.
Measured: up to 6 months
Secondary outcomes (3)
Toxicity as assessed by number of participants experiencing adverse events Grade 3 or higher as defined by CTCAE v2.0
Measured: up to 6 months
Pharmacokinetics of Azacitidine combined with Phenylbutyrate as measured by maximal plasma concentration (Cmax)
Measured: Up to 24 hours
Gene-re-expression of epigenetic modulation in Peripheral Blood Mononuclear Cells (PBMC) as measured by change in Epstein-Barr Virus (EBV) viral load (number of copies per 1 million cells) after treatment with Azacitidine
Measured: Change from baseline to up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startMar 2000
- Primary completionJul 2005
- Study completionJul 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Michael A. Carducci, MD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005639
- Sponsor's protocol ID
- J9982
- Other IDs
- U01CA070095, R01CA075525, P50CA058236, P30CA006973, CDR0000067799, NCI-270, 99-12-03-02
- Status last verified
- Jan 2019
- First submitted
- 2 May 2000
- Last updated
- 11 Jan 2019
- Results posted
- No
Publications
Lin J, Gilbert J, Rudek MA, Zwiebel JA, Gore S, Jiemjit A, Zhao M, Baker SD, Ambinder RF, Herman JG, Donehower RC, Carducci MA. A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors. Clin Cancer Res. 2009 Oct 1;15(19):6241-9. doi: 10.1158/1078-0432.CCR-09-0567. Epub 2009 Sep 29.
PubMed 19789320
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation to Maximally Tolerated Dose Trial of 5-Azacytidine (5 AC, NSC 102816) in Combination With Sodium Phenylbutyrate (PB, NSC 657802) in Patients With Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT00005639
- Acronym / sponsor ID
- J9982
- Keywords
- stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, small intestine lymphoma, unspecified adult solid tumor, protocol specific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2000 (actual)
- Primary completion
- Jul 2005 (actual)
- Study completion
- Jul 2005 (actual)
- First posted
- 27 Jan 2003 (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.
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of azacitidine plus phenylbutyrate in treating patients with advanced or metastatic solid tumors that have not responded to previous treatment.
Detailed description
OBJECTIVES:
- Evaluate the safety and toxicity of azacitidine plus phenylbutyrate in patients with refractory solid tumors.
- Determine the maximum tolerated dose of this treatment regimen where maximal gene reexpression occurs in these patients.
- Evaluate the pharmacokinetics of these drugs in these patients.
- Determine the minimally effective dose of azacitidine in combination with phenylbutyrate that elicits a biological or clinical response in these patients.
OUTLINE: This is a dose escalation study.
Patients receive azacitidine subcutaneously for 14-21 days and sodium phenylbutyrate IV continuously for 1-7 days. Treatment repeats every 35 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses and durations of treatment with azacitidine and phenylbutyrate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.
PROJECTED ACCRUAL: Approximately 3-50 patients will be accrued for this study within 12-18 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Regimen A: 14-day 5-AC with intermittent phenylbutyrate | Experimental | Drug: Azacitidine Injection, Drug: sodium phenylbutyrateParticipants receive low-dose regimen of 5-AC with intermittent phenylbutyrate 400 mg/m2/day by continuous intravenous (CIV) over 24 hours on Days 6 and 13. Each cycle lasts 35 days. Cohort A1: 25 mg/m2/day subcutaneous (SC) Cohort A-1: 18.75 mg/m2/day SC Cohort A-2: 15 mg/m2/day SC Cohort A-3: 10 mg/m2/day SC |
| Regimen B: 7-day 5-AC with sequential phenylbutyrate | Experimental | Drug: Azacitidine Injection, Drug: sodium phenylbutyrateParticipants receive 5-AC 75mg/m2/day SC for 7 days, followed sequentially by two different doses of phenylbutyrate CIV starting on Day 8 and continuing for 7 days. Each cycle lasts 35 days Cohort B1: Phenylbutyrate 200 mg/m2/day CIV Cohort B2: Phenylbutyrate 400 mg/m2/day CIV |
| Regimen C: 21-day 5-AC with weekly phenylbutyrate | Experimental | Drug: Azacitidine Injection, Drug: sodium phenylbutyrateParticipants receive two different daily doses of 5-AC SC for 21 days and phenylbutyrate 400 mg/m2/day CIV over 24 hours once-per-week. Each cycle lasts 42 days. Cohort C1: 5-AC 10mg/m2/day SC Cohort C2: 5-AC 12.5mg/m2/day SC |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (39 listed)
- Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor not amenable to curative therapy
- Progressive disease
- Evaluable disease
- No CNS metastases by CT scan or MRI
- 18 and over
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Azacitidine InjectionAlso: AC, 5-ACsubcutaneous injection (SC) | Drug | Regimen A: 14-day 5-AC with intermittent phenylbutyrate, Regimen B: 7-day 5-AC with sequential phenylbutyrate, Regimen C: 21-day 5-AC with weekly phenylbutyrate |
| sodium phenylbutyratecontinuous intravenous (CIV) | Drug | Regimen A: 14-day 5-AC with intermittent phenylbutyrate, Regimen B: 7-day 5-AC with sequential phenylbutyrate, Regimen C: 21-day 5-AC with weekly phenylbutyrate |
Primary outcome
Minimal Effective Dose (MED) of Azacitidine with Phenylbutyrate
Time frame: up to 6 months
MED (milligrams) of combined Azacitidine and Phenylbutyrate that results in clinical response, as defined by Standard World Health Organization (WHO) criteria and/or target inhibition.
3 secondary outcomes
Toxicity as assessed by number of participants experiencing adverse events Grade 3 or higher as defined by CTCAE v2.0
Time frame: up to 6 months
Pharmacokinetics of Azacitidine combined with Phenylbutyrate as measured by maximal plasma concentration (Cmax)
Time frame: Up to 24 hours
Gene-re-expression of epigenetic modulation in Peripheral Blood Mononuclear Cells (PBMC) as measured by change in Epstein-Barr Virus (EBV) viral load (number of copies per 1 million cells) after treatment with Azacitidine
Time frame: Change from baseline to up to 6 months
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 11 Jan 2019.
- Results publication: PubMed 19789320Lin J, Gilbert J, Rudek MA, Zwiebel JA, Gore S, Jiemjit A, Zhao M, Baker SD, Ambinder RF, Herman JG, Donehower RC, Carducci MA. A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors. Clin Cancer Res. 2009 Oct 1;15(19):6241-9. doi: 10.1158/1078-0432.CCR-09-0567. Epub 2009 Sep 29.
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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.
Michael A. Carducci, MD study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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 Azacitidine Injection and sodium phenylbutyrate in people with Lymphoma and Small Intestine Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 39 inclusion and 0 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 11 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?
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?
Minimal Effective Dose (MED) of Azacitidine with Phenylbutyrate (time frame: up to 6 months). 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 NCT00005639, which also lists 1 linked publication.
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 11 Jan 2019.