Ciliary Body and Choroid Melanoma, Medium/Large SizePhase 2NCT01100528
Dacarbazine and Recombinant Interferon Alfa-2b in Treating Patients With Primary Uveal Melanoma With Genetic Imbalance
A Phase 2 study testing recombinant interferon alfa-2b, dacarbazine and laboratory biomarker analysis in people with Ciliary Body and Choroid Melanoma, Medium/Large Size and Ciliary Body and Choroid Melanoma, Small Size, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Recombinant interferon alfa-2b may interfere with the growth of tumor cells. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Iris Melanoma
- What is being tested?
- recombinant interferon alfa-2b, dacarbazine and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Nov 2009to 14 Dec 2017
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have a diagnosis, either cytologic or histologic, of melanoma of the iris, ciliary body and/or choroid
- Patient's tumor must exhibit monosomy 3 and/or 8q amplification as determined by karyotype, comparative genomic hybridization (CGH), polymerase chain reaction (PCR)-based microsatellite, and/or Fluorescence in situ Hybridization (FISH) analysis; tissue or cells for analysis can be obtained at enucleation, resection, or by fine needle aspirate (FNA).
- Patients must have undergone adequate primary therapy; this can include enucleation, brachytherapy, proton beam radiotherapy, stereotactic irradiation, trans-scleral local resection, transretinal resection or diode laser thermotherapy
- Patients must have had chest X-ray and hepatic ultrasound or other imaging methods such as CT or MRI to eliminate distant disease
- Patients must have a performance status (ECOG) of < 2
- Patients must be entered within 56 days of completing primary therapy
Show all 19Show fewer
- White blood count (WBC) ≥ 3.0 x 10^9/L
- Neutrophils ≥ 1.5 x 10^9/L
- Platelets ≥ 100 x 10^9/L
- international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.5 x upper limit of normal
- Hemoglobin ≥ 10 gm/100 ml
- Creatinine ≤ 2 mg/dl
- Bilirubin (total) ≤ 1.5 mg/dl
- Alanine transaminase (ALT) ≤ 1.5 x upper limit of normal
- Alkaline phosphatase ≤ 1.5 x upper limit of normal
- Aspartate aminotransferase (AST) ≤ 1.5 x upper limit of normal
- Patients must not have received any other systemic therapy for melanoma
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- All patients must be informed of the investigational nature of this study and must provide written informed consent in accordance with institutional and federal guidelines; a copy of the informed consent document signed by the patient must be given to the patient
Who cannot join
- Patients with metastasis
- Patients that are pregnant or breastfeeding
- Patients may not be receiving any other investigational agents
- Patients with a history of immunodeficiency or autoimmune diseases are not eligible; patients requiring therapy with corticosteroids or other immunosuppressives are not eligible; patients requiring ongoing replacement therapy with physiologic doses of corticosteroids will be eligible.
- Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible
- Patients who are known to be positive for HIV or Hepatitis B Surface Antigen (HepBAg)
- No patient may have had a malignancy other than a malignant melanoma, with the following exceptions: basal or squamous cell carcinomas of the skin; carcinoma in-situ of the uterine cervix; any malignancy treated with curative intent and in complete remission for > 3 years
- Patients with organ allografts
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: Adjuvant Therapy for Patients With Primary Uveal Melanoma With Genetic Imbalance
RATIONALE: Drugs used in chemotherapy, such as dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Recombinant interferon alfa-2b may interfere with the growth of tumor cells. Giving interferon alfa-2b together with dacarbazine may be an effective treatment for primary uveal melanoma.
PURPOSE: This phase II trial is studying how well giving dacarbazine together with recombinant interferon alfa-2b works in treating patients with primary uveal melanoma with genetic imbalance.
Read the detailed description
PRIMARY OBJECTIVES:
- Assess disease-free survival (DFS) with sequential dacarbazine and interferon-alfa-2b as an adjuvant to primary therapy for patients with uveal melanoma with genetic imbalance.
SECONDARY OBJECTIVES:
- Evaluate side effects and assess safety in the patient population.
II. Examine the relationship between the levels of plasma biomarkers of immune function and tumor invasion and the clinical outcome.
OUTLINE: Patients receive dacarbazine IV on days 1 and 29. Beginning 4 weeks after the second dose of dacarbazine, patients receive recombinant interferon alfa-2b subcutaneously 3 times a week for 24 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 6 months.
- Conditions
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Iris Melanoma, Recurrent Intraocular Melanoma
- Being tested
- recombinant interferon alfa-2b, dacarbazine, laboratory biomarker analysis
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant interferon alfa-2bBiological
Also called Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B
Given subcutaneously (SC) 3 times a week for 24 weeks
dacarbazineDrug
Also called Asercit, Biocarbazine, Dacarbazina Almirall, DIC
Given IV on days 1 and 29
laboratory biomarker analysisOther
Correlative studies obtained prior to therapy, every 8 weeks while on therapy, and then every 6 months during follow-up
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive dacarbazine IV on days 1 and 29. Beginning 4 weeks after the second dose of dacarbazine, patients receive recombinant interferon alfa-2b subcutaneously 3 times a week for 24 weeks in the absence of disease progression or unacceptable toxicity. Receives: Biological: recombinant interferon alfa-2b; Drug: dacarbazine; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Disease-free Survival (DFS)
DFS will be calculated from the date treatment starts to the date of documented recurrence or death. It will be summarized using the method of Kaplan and Meier. Treatment will be considered relatively ineffective in this population if the underlying 2-year DFS is <60%, whereas the combination will be considered promising if the underlying rate is >80%.
Measured: 5 years from time-of-enrollment
Secondary outcomes (2)
Number of Participants With Toxicity or Grade 4 Adverse Events Via CTCAE Version 3.0
Number of participants with toxicity as defined as an underlying risk of >33% Grade 3 (non blood/bone marrow) or Grade 4 adverse events that are related to therapy, assessed by NCI CTCAE version 3.0
Measured: up to 32 weeks from start of study
Changes in Plasma Biomarkers and Their Association With DFS
Plasma levels of these markers will be summarized at baseline and over time quantitatively and graphically. Specific regulators of immune escape and tumor cell invasion identified in uveal melanoma gene array studies will be measured. Peripheral blood cells and plasma will be analyzed for granulysin (a measure of natural killer cells (NK) activity), beta2-microglobulin, autotoxin, lysophosphatidic acid (a product of autotaxin), matrix metalloproteinase-7, tissue inhibitor of matrix metalloproteinase, and soluble E-cadherin.
Measured: 5 yrs from start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2010 (estimated)
- Study start11 Nov 2009
- Primary completion25 Jul 2015
- Study completion14 Dec 2017
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 Case Comprehensive Cancer CenterThe 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
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yogen Saunthararajah, MD, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01100528
- Sponsor's protocol ID
- CASE2609
- Other IDs
- NCI-2010-00640
- Status last verified
- Feb 2019
- First submitted
- 7 Apr 2010
- Last updated
- 26 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Binkley E, Triozzi PL, Rybicki L, Achberger S, Aldrich W, Singh A. A prospective trial of adjuvant therapy for high-risk uveal melanoma: assessing 5-year survival outcomes. Br J Ophthalmol. 2020 Apr;104(4):524-528. doi: 10.1136/bjophthalmol-2019-314461. Epub 2019 Aug 1.
PubMed 31371315
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjuvant Therapy for Patients With Primary Uveal Melanoma With Genetic Imbalance
- ClinicalTrials.gov ID
- NCT01100528
- Acronym / sponsor ID
- CASE2609
- Conditions
- Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Iris Melanoma, Recurrent Intraocular Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 11 Nov 2009 (actual)
- Primary completion
- 25 Jul 2015 (actual)
- Study completion
- 14 Dec 2017 (actual)
- First posted
- 9 Apr 2010 (estimated)
- Results
- Posted 29 Oct 2018
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, such as dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Recombinant interferon alfa-2b may interfere with the growth of tumor cells. Giving interferon alfa-2b together with dacarbazine may be an effective treatment for primary uveal melanoma.
PURPOSE: This phase II trial is studying how well giving dacarbazine together with recombinant interferon alfa-2b works in treating patients with primary uveal melanoma with genetic imbalance.
Detailed description
PRIMARY OBJECTIVES:
- Assess disease-free survival (DFS) with sequential dacarbazine and interferon-alfa-2b as an adjuvant to primary therapy for patients with uveal melanoma with genetic imbalance.
SECONDARY OBJECTIVES:
- Evaluate side effects and assess safety in the patient population.
II. Examine the relationship between the levels of plasma biomarkers of immune function and tumor invasion and the clinical outcome.
OUTLINE: Patients receive dacarbazine IV on days 1 and 29. Beginning 4 weeks after the second dose of dacarbazine, patients receive recombinant interferon alfa-2b subcutaneously 3 times a week for 24 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 6 months.
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 | Biological: recombinant interferon alfa-2b, Drug: dacarbazine, Other: laboratory biomarker analysisPatients receive dacarbazine IV on days 1 and 29. Beginning 4 weeks after the second dose of dacarbazine, patients receive recombinant interferon alfa-2b subcutaneously 3 times a week for 24 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Patients must have a diagnosis, either cytologic or histologic, of melanoma of the iris, ciliary body and/or choroid
- Patient's tumor must exhibit monosomy 3 and/or 8q amplification as determined by karyotype, comparative genomic hybridization (CGH), polymerase chain reaction (PCR)-based microsatellite, and/or Fluorescence in situ Hybridization (FISH) analysis; tissue or cells for analysis can be obtained at enucleation, resection, or by fine needle aspirate (FNA).
- Patients must have undergone adequate primary therapy; this can include enucleation, brachytherapy, proton beam radiotherapy, stereotactic irradiation, trans-scleral local resection, transretinal resection or diode laser thermotherapy
- Patients must have had chest X-ray and hepatic ultrasound or other imaging methods such as CT or MRI to eliminate distant disease
- Patients must have a performance status (ECOG) of < 2
Key exclusion criteria (8 listed)
- Patients with metastasis
- Patients that are pregnant or breastfeeding
- Patients may not be receiving any other investigational agents
- Patients with a history of immunodeficiency or autoimmune diseases are not eligible; patients requiring therapy with corticosteroids or other immunosuppressives are not eligible; patients requiring ongoing replacement therapy with physiologic doses of corticosteroids will be eligible.
- Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible
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 |
|---|---|---|
| recombinant interferon alfa-2bAlso: Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2BGiven subcutaneously (SC) 3 times a week for 24 weeks | Biological | Arm I |
| dacarbazineAlso: Asercit, Biocarbazine, Dacarbazina Almirall, DICGiven IV on days 1 and 29 | Drug | Arm I |
| laboratory biomarker analysisCorrelative studies obtained prior to therapy, every 8 weeks while on therapy, and then every 6 months during follow-up | Other | Arm I |
Primary outcome
Number of Patients With Disease-free Survival (DFS)
Time frame: 5 years from time-of-enrollment
DFS will be calculated from the date treatment starts to the date of documented recurrence or death. It will be summarized using the method of Kaplan and Meier. Treatment will be considered relatively ineffective in this population if the underlying 2-year DFS is <60%, whereas the combination will be considered promising if the underlying rate is >80%.
2 secondary outcomes
Number of Participants With Toxicity or Grade 4 Adverse Events Via CTCAE Version 3.0
Time frame: up to 32 weeks from start of study
Changes in Plasma Biomarkers and Their Association With DFS
Time frame: 5 yrs from start of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31371315Binkley E, Triozzi PL, Rybicki L, Achberger S, Aldrich W, Singh A. A prospective trial of adjuvant therapy for high-risk uveal melanoma: assessing 5-year survival outcomes. Br J Ophthalmol. 2020 Apr;104(4):524-528. doi: 10.1136/bjophthalmol-2019-314461. Epub 2019 Aug 1.
Related trials for Ciliary Body and Choroid Melanoma, Medium/Large Size
Active, not recruitingPhase 2
Sunitinib Malate or Valproic Acid in Preventing Metastasis in Patients With High-Risk Uveal Melanoma
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.
Yogen Saunthararajah, MD principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing recombinant interferon alfa-2b, dacarbazine and laboratory biomarker analysis in people with Ciliary Body and Choroid Melanoma, Medium/Large Size and Ciliary Body and Choroid Melanoma, Small Size, run by Case Comprehensive Cancer Center 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 19 inclusion and 8 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 26 Feb 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 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 29 Oct 2018). 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?
Number of Patients With Disease-free Survival (DFS) (time frame: 5 years from time-of-enrollment). 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 NCT01100528, 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 26 Feb 2019.