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Dacarbazine and Recombinant Interferon Alfa-2b in Treating Patients With Primary Uveal Melanoma With Genetic Imbalance

Primary Purpose

Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Iris Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
recombinant interferon alfa-2b
dacarbazine
laboratory biomarker analysis
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ciliary Body and Choroid Melanoma, Medium/Large Size

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion

  • 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
  • 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

Exclusion

  • 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

Sites / Locations

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

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.

Outcomes

Primary Outcome Measures

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%.

Secondary Outcome Measures

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
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.

Full Information

First Posted
April 7, 2010
Last Updated
February 11, 2019
Sponsor
Case Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT01100528
Brief Title
Dacarbazine and Recombinant Interferon Alfa-2b in Treating Patients With Primary Uveal Melanoma With Genetic Imbalance
Official Title
Adjuvant Therapy for Patients With Primary Uveal Melanoma With Genetic Imbalance
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
November 11, 2009 (Actual)
Primary Completion Date
July 25, 2015 (Actual)
Study Completion Date
December 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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: I. 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: I. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Iris Melanoma, Recurrent Intraocular Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
recombinant interferon alfa-2b
Other Intervention Name(s)
Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, interferon alfa-2B, Intron A
Intervention Description
Given subcutaneously (SC) 3 times a week for 24 weeks
Intervention Type
Drug
Intervention Name(s)
dacarbazine
Other Intervention Name(s)
Asercit, Biocarbazine, Dacarbazina Almirall, DIC, DTIC, DTIC-Dome
Intervention Description
Given IV on days 1 and 29
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies obtained prior to therapy, every 8 weeks while on therapy, and then every 6 months during follow-up
Primary Outcome Measure Information:
Title
Number of Patients With Disease-free Survival (DFS)
Description
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%.
Time Frame
5 years from time-of-enrollment
Secondary Outcome Measure Information:
Title
Number of Participants With Toxicity or Grade 4 Adverse Events Via CTCAE Version 3.0
Description
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
Time Frame
up to 32 weeks from start of study
Title
Changes in Plasma Biomarkers and Their Association With DFS
Description
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.
Time Frame
5 yrs from start of treatment

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion 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 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 Exclusion 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yogen Saunthararajah, MD
Organizational Affiliation
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31371315
Citation
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.
Results Reference
derived

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Dacarbazine and Recombinant Interferon Alfa-2b in Treating Patients With Primary Uveal Melanoma With Genetic Imbalance

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