Clinical trial NCT01100528: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ciliary Body and Choroid Melanoma, Medium/Large Size
Ciliary Body and Choroid Melanoma, Small Size
Iris Melanoma
Recurrent Intraocular Melanoma
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2010-04-09
Enrollment: 38
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Patients With Disease-free Survival (DFS)
timeFrame: 5 years from time-of-enrollment
Secondary outcomes:
measure: Number of Participants With Toxicity or Grade 4 Adverse Events Via CTCAE Version 3.0
timeFrame: up to 32 weeks from start of study
measure: Changes in Plasma Biomarkers and Their Association With DFS
timeFrame: 5 yrs from start of treatment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Yogen Saunthararajah, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.