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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01100528
First received: April 7, 2010
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Ciliary Body and Choroid Melanoma, Medium/Large Size
Ciliary Body and Choroid Melanoma, Small Size
Iris Melanoma
Recurrent Intraocular Melanoma
Biological: recombinant interferon alfa-2b
Drug: dacarbazine
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adjuvant Therapy for Patients With Primary Uveal Melanoma With Genetic Imbalance

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Disease-free survival(DFS) [ Time Frame: 2 yrs from start of treatment ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: Yes ]
    As assessed by NCI CTCAE version 3.0

  • Changes in plasma biomarkers and their association with DFS [ Time Frame: 2 yrs from start of treatment ] [ Designated as safety issue: No ]
    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 NK activity), beta2-microglobulin, autotoxin, lysophosphatidic acid (a product of autotaxin), matrix metalloproteinase-7, tissue inhibitor of matrix metalloproteinase, and soluble E-cadherin.


Estimated Enrollment: 36
Study Start Date: November 2009
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: recombinant interferon alfa-2b
Given 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

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, CGH, PCR-based microsatellite, and/or FISH analysis; tissue or cells for analysis can be obtained at enucleation, resection, or by 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
  • WBC >= 3.0 x 10^9/L
  • Neutrophils >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • INR and PTT < 1.5 x upper limit of normal
  • Hemoglobin >= 10 gm/100 ml
  • Creatinine =< 2 mg/dl
  • Bilirubin (total) =< 1.5 mg/dl
  • ALT =< 1.5 x upper limit of normal
  • Alkaline phosphatase =< 1.5 x upper limit of normal
  • 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01100528

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Pierre Triozzi Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01100528     History of Changes
Other Study ID Numbers: CASE2609, NCI-2010-00640
Study First Received: April 7, 2010
Last Updated: February 7, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Interferon-alpha
Interferons
Dacarbazine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014