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

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ClinicalTrials.gov Identifier: NCT01100528
Recruitment Status : Completed
First Posted : April 9, 2010
Results First Posted : October 29, 2018
Last Update Posted : February 26, 2019
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE April 7, 2010
First Posted Date  ICMJE April 9, 2010
Results First Submitted Date  ICMJE September 25, 2018
Results First Posted Date  ICMJE October 29, 2018
Last Update Posted Date February 26, 2019
Actual Study Start Date  ICMJE November 11, 2009
Actual Primary Completion Date July 25, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2018)
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%.
Original Primary Outcome Measures  ICMJE
 (submitted: April 7, 2010)
Disease-free survival [ Time Frame: every 8 weeks while on therapy, and then every 6 months during follow-up ]
Specific regulators of immune escape and tumor cell invasion identified in uveal melanoma gene array studies will be measured. Peripheral blood will be obtained prior to therapy, every 8 weeks while on therapy, and then every 6 months during follow-up
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2018)
  • 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 ]
    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 [ Time Frame: 5 yrs from start of treatment ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2010)
  • Side effects and safety as assessed by NCI CTCAE version 3.0 [ Time Frame: 3 times a week for 24 weeks in the absence of unacceptable toxicity ]
    As assessed by NCI CTCAE version 3.0
  • Relationship between the levels of plasma biomarkers and clinical outcome [ Time Frame: every 8 weeks while on therapy, and then every 6 months during follow-up ]
    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 NK activity), beta2-microglobulin, autotoxin, lysophosphatidic acid (a product of autotaxin), matrix metalloproteinase-7, tissue inhibitor of matrix metalloproteinase, and soluble E-cadherin.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dacarbazine and Recombinant Interferon Alfa-2b in Treating Patients With Primary Uveal Melanoma With Genetic Imbalance
Official Title  ICMJE Adjuvant Therapy for Patients With Primary Uveal Melanoma With Genetic Imbalance
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ciliary Body and Choroid Melanoma, Medium/Large Size
  • Ciliary Body and Choroid Melanoma, Small Size
  • Iris Melanoma
  • Recurrent Intraocular Melanoma
Intervention  ICMJE
  • Biological: recombinant interferon alfa-2b
    Given subcutaneously (SC) 3 times a week for 24 weeks
    Other Names:
    • Alfatronol
    • Glucoferon
    • Heberon Alfa
    • IFN alpha-2B
    • interferon alfa-2B
    • Intron A
  • Drug: dacarbazine
    Given IV on days 1 and 29
    Other Names:
    • Asercit
    • Biocarbazine
    • Dacarbazina Almirall
    • DIC
    • DTIC
    • DTIC-Dome
  • Other: laboratory biomarker analysis
    Correlative studies obtained prior to therapy, every 8 weeks while on therapy, and then every 6 months during follow-up
Study Arms  ICMJE Experimental: Arm I
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.
Interventions:
  • Biological: recombinant interferon alfa-2b
  • Drug: dacarbazine
  • Other: laboratory biomarker analysis
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 28, 2016)
38
Original Estimated Enrollment  ICMJE
 (submitted: April 7, 2010)
36
Actual Study Completion Date  ICMJE December 14, 2017
Actual Primary Completion Date July 25, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01100528
Other Study ID Numbers  ICMJE CASE2609
NCI-2010-00640 ( Other Identifier: NCI/CTRP )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yogen Saunthararajah, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP