Ciliary Body and Choroid Melanoma, Medium/Large SizePhase 2NCT00121225
Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma
A Phase 2 study testing vorinostat in people with Ciliary Body and Choroid Melanoma, Medium/Large Size and Extraocular Extension Melanoma, run by National Cancer Institute (NCI) at 5 sites in 2 countries.
Trial summary
This phase II trial is studying how well vorinostat works in treating patients with metastatic or unresectable melanoma. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma
- What is being tested?
- vorinostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Sep 2005to Jun 2013
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically/cytologically confirmed melanoma that is metastatic/unresectable
- Residual, recurrent, or metastatic disease by radiographic examination. Measurable disease (at least 1 lesion in at least 1 dimension (longest diameter) as >20mm with conventional techniques or >10mm with spiral CT scan, within 4 weeks prior to registration
- No prior therapy or 1 prior treatment (cytokine/chemotherapy/combination) for metastatic disease allowed. Patients should not take valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment. At least 4 weeks from prior therapy to be eligible or 6 weeks if last regimen included BCNU or mitomycin C
- Age>=18 years
- Life expectancy >=3 months.
- ECOG<2 (Karnofsky ≥60%)
Show all 17Show fewer
- Leukocytes >3,000/mcL
- Absolute neutrophil count >1,500/mcL
- Platelets >100,000/mcL
- Total bilirubin within institutional limits
- AST/ALT≤2.5Xinstitutional ULN
- Creatinine within institutional limits OR creatinine clearance >60mL/min/1.73 m2 if creatinine levels above institutional limits
- Eligibility of patients taking medications with potential to affect activity/PK of Vorinostat will be determined by PI
- Must not use concomitant steroids except topical/inhaled use
- Vorinostat effects on developing human fetus are unknown. Women of childbearing potential (WOCBP) and sexually active males must agree to use accepted/effective contraception method prior to study entry and for duration of the study
- Ability to understand/willingness to sign written informed consent
- Must have paraffin block of tumor tissue available for future studies
Who cannot join
- Chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study
- May not be receiving any other investigational agents
- Known brain metastases
- History of allergic reactions attributed to compounds of similar chemical/biologic composition to Vorinostat
- Uncontrolled intercurrent illness including but not limited to ongoing/active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women excluded because Vorinostat is a HDAC inhibitor agent with potential for teratogenic or abortifacient effects
- HIV-positive patients receiving combination antiretroviral therapy are ineligible because of potential for PK interactions with Vorinostat
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Canada3 sites
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
Princess Margaret Hospital Phase 2 Consortium
Toronto, Ontario, M5G 2M9
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
United States2 sites
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
Fox Chase Cancer Center
Rockledge, Pennsylvania, 19046
About this study
Official title: A Phase II Study of Vorinostat in Patients With Advanced Melanoma
This phase II trial is studying how well vorinostat works in treating patients with metastatic or unresectable melanoma. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Read the detailed description
PRIMARY OBJECTIVE:
- Determine the objective response rate in patients with metastatic or unresectable melanoma treated with vorinostat.
SECONDARY OBJECTIVES:
- Determine time to progression in patients treated with this drug. II. Determine the utility of HP1 and/or macro H2A nuclear foci as biomarkers of response in patients treated with this drug.
III. Correlate the presence of 72R or 72P variant p53 polymorphisms with response and time to progression in patients treated with this drug.
IV. Determine gene expression profiles that may predict response to this drug and gene expression changes that occur after treatment with this drug in these patients.
OUTLINE: This is a multicenter study.
Patients receive oral vorinostat once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for 4 weeks and then every 3 months thereafter.
- Conditions
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma, Uveal Melanoma, Recurrent Intraocular Melanoma, Recurrent Melanoma
- Being tested
- vorinostat
- Medical subject headings
- Uveal Melanoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vorinostatDrug
Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter.
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. Receives: Drug: vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)
Per Response Evaluation Criteria in Solid Tumours Criteria (RECIST v1.0) for target lesions and are assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in sum of longest diameter of target lesions; Objective Response (OR) = CR+ PR.
Measured: Up to 5 years
Secondary outcomes (4)
Time to Progression Assessed by RECIST
Measured: Up to 5 years
Difference in HP1 and MacroH2A Nuclear Foci Expression Between Progressive Minus Stable Disease Outcomes
Macro H2A and HP1 expression levels were compared through analysis of log fold changes in antibody expression in a multivariate general linear model between progressive disease and stable disease outcomes.
Measured: Baseline and day 15
Number of Patients With p53 Allelic Variations (72R or 72P)
Participants were assessed for p53 allelic variation at baseline
Measured: Baseline
Comparison of VEGF Serum Levels to Response to Vorinostat
Blood specimens were collected from participants on Day 1 Cycle 1 prior to treatment (baseline), Day 1 3-4 hours following Vorinostat ingestion, Day 8 and Day 15. VEGF serum concentrations were detected using the Luminex multiplexed assay, where the median fluorescence intensity results were analyzed by a weighted five-parameter logistic method. The values were averaged across all time points per participant.
Measured: Baseline, Day 1, Day 8 and Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2005 (estimated)
- Study startSep 2005
- Primary completionMar 2009
- Study completionJun 2013
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 (1)Papers the sponsor has linked to this study.
- Other trials for Ciliary Body and Choroid Melanoma, Medium/Large SizeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Naomi Balzer-Haas, Principal investigator, Princess Margaret Hospital Phase 2 Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00121225
- Sponsor's protocol ID
- NCI-2009-00099
- Other IDs
- PHL-040, CDR0000436851, N01CM62203
- Status last verified
- Jan 2019
- First submitted
- 19 Jul 2005
- Last updated
- 29 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Haas NB, Quirt I, Hotte S, McWhirter E, Polintan R, Litwin S, Adams PD, McBryan T, Wang L, Martin LP, vonMehren M, Alpaugh RK, Zweibel J, Oza A. Phase II trial of vorinostat in advanced melanoma. Invest New Drugs. 2014 Jun;32(3):526-34. doi: 10.1007/s10637-014-0066-9. Epub 2014 Jan 25.
PubMed 24464266
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Vorinostat in Patients With Advanced Melanoma
- ClinicalTrials.gov ID
- NCT00121225
- Acronym / sponsor ID
- NCI-2009-00099
- Conditions
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma, Uveal Melanoma, Recurrent Intraocular Melanoma, Recurrent Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2005
- Primary completion
- Mar 2009 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 21 Jul 2005 (estimated)
- Results
- Posted 3 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well vorinostat works in treating patients with metastatic or unresectable melanoma. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Detailed description
PRIMARY OBJECTIVE:
- Determine the objective response rate in patients with metastatic or unresectable melanoma treated with vorinostat.
SECONDARY OBJECTIVES:
- Determine time to progression in patients treated with this drug. II. Determine the utility of HP1 and/or macro H2A nuclear foci as biomarkers of response in patients treated with this drug.
III. Correlate the presence of 72R or 72P variant p53 polymorphisms with response and time to progression in patients treated with this drug.
IV. Determine gene expression profiles that may predict response to this drug and gene expression changes that occur after treatment with this drug in these patients.
OUTLINE: This is a multicenter study.
Patients receive oral vorinostat once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for 4 weeks and then every 3 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: vorinostatPatients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically/cytologically confirmed melanoma that is metastatic/unresectable
- Residual, recurrent, or metastatic disease by radiographic examination. Measurable disease (at least 1 lesion in at least 1 dimension (longest diameter) as >20mm with conventional techniques or >10mm with spiral CT scan, within 4 weeks prior to registration
- No prior therapy or 1 prior treatment (cytokine/chemotherapy/combination) for metastatic disease allowed. Patients should not take valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment. At least 4 weeks from prior therapy to be eligible or 6 weeks if last regimen included BCNU or mitomycin C
- Age>=18 years
- Life expectancy >=3 months.
Key exclusion criteria (7 listed)
- Chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study
- May not be receiving any other investigational agents
- Known brain metastases
- History of allergic reactions attributed to compounds of similar chemical/biologic composition to Vorinostat
- Uncontrolled intercurrent illness including but not limited to ongoing/active infection, symptomatic congestive heart failure, unstable angina pectoris, 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 |
|---|---|---|
| vorinostatAlso: L-001079038, SAHA, suberoylanilide hydroxamic acid, ZolinzaPatients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. | Drug | Arm I |
Primary outcome
Objective Response Rate Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)
Time frame: Up to 5 years
Per Response Evaluation Criteria in Solid Tumours Criteria (RECIST v1.0) for target lesions and are assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in sum of longest diameter of target lesions; Objective Response (OR) = CR+ PR.
4 secondary outcomes
Time to Progression Assessed by RECIST
Time frame: Up to 5 years
Difference in HP1 and MacroH2A Nuclear Foci Expression Between Progressive Minus Stable Disease Outcomes
Time frame: Baseline and day 15
Number of Patients With p53 Allelic Variations (72R or 72P)
Time frame: Baseline
Comparison of VEGF Serum Levels to Response to Vorinostat
Time frame: Baseline, Day 1, Day 8 and Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24464266Haas NB, Quirt I, Hotte S, McWhirter E, Polintan R, Litwin S, Adams PD, McBryan T, Wang L, Martin LP, vonMehren M, Alpaugh RK, Zweibel J, Oza A. Phase II trial of vorinostat in advanced melanoma. Invest New Drugs. 2014 Jun;32(3):526-34. doi: 10.1007/s10637-014-0066-9. Epub 2014 Jan 25.
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Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size
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.
Naomi Balzer-Haas principal investigator
Princess Margaret Hospital Phase 2 Consortium
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing vorinostat in people with Ciliary Body and Choroid Melanoma, Medium/Large Size and Extraocular Extension Melanoma, run by National Cancer Institute (NCI) at 5 sites in 2 countries.
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 7 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 29 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 5 sites in Canada, 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 Oct 2014). 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?
Objective Response Rate Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) (time frame: Up to 5 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 NCT00121225, 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 29 Jan 2019.