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

NCT01100528 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CASE2609NCI-2010-00640
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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%.

  5 years from time-of-enrollment

Secondary Outcomes (2)

• Number of Participants With Toxicity or Grade 4 Adverse Events Via CTCAE Version 3.0

  up to 32 weeks from start of study

• Changes in Plasma Biomarkers and Their Association With DFS

  5 yrs from start of treatment

Study Arms (1)

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.

Biological: recombinant interferon alfa-2b; Drug: dacarbazine; Other: laboratory biomarker analysis

Interventions

recombinant interferon alfa-2b BIOLOGICAL

Given subcutaneously (SC) 3 times a week for 24 weeks

Also known as: Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B, interferon alfa-2B, Intron A

Arm I

dacarbazine DRUG

Given IV on days 1 and 29

Also known as: Asercit, Biocarbazine, Dacarbazina Almirall, DIC, DTIC, DTIC-Dome

Arm I

laboratory biomarker analysis OTHER

Correlative studies obtained prior to therapy, every 8 weeks while on therapy, and then every 6 months during follow-up

Arm I

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• 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.

  PMID: 31371315 DERIVED

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Introns; Interferon alpha-2; Dacarbazine

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Yogen Saunthararajah, MD
• Organization: Cleveland Clinic, Case Comprehensive Cancer Center

CancerCenterResearch@ccf.org

866-223-8100

Study Officials

• Yogen Saunthararajah, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2010
• First Posted: April 9, 2010
• Study Start: November 11, 2009
• Primary Completion: July 25, 2015
• Study Completion: December 14, 2017
• Last Updated: February 26, 2019
• Results First Posted: October 29, 2018

Record last verified: 2019-02

Locations

US (1)