Interleukin-2 With or Without Histamine Dihydrochloride in Treating Patients With Stage IV Melanoma Metastatic to the Liver

Sponsor

Maxim Pharmaceuticals (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00039234

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Study Details

Study Description

Brief Summary

RATIONALE: Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Histamine dihydrochloride may help interleukin-2 kill more tumor cells by making tumor cells more sensitive to the drug. It is not yet known if interleukin-2 is more effective with or without histamine dihydrochloride in treating stage IV melanoma that is metastatic to the liver.

PURPOSE: Randomized phase III trial to compare the effectiveness of interleukin-2 with or without histamine dihydrochloride in treating patients who have stage IV melanoma that is metastatic to the liver.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin) Metastatic Cancer	Biological: aldesleukin Drug: histamine dihydrochloride	Phase 3

Detailed Description

OBJECTIVES:

Compare the duration of survival in patients with stage IV melanoma with hepatic metastasis treated with interleukin-2 with or without histamine dihydrochloride.
Compare the progression-free survival, response rate, response rate of hepatic tumors, and lack of disease progression in patients treated with these regimens.
Determine the safety of these regimens, in terms of frequency, severity, and causal relationship of adverse events, in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center location (North America vs Europe), lactate dehydrogenase (less than ULN vs ULN or greater), and metastatic sites (liver only vs liver and other sites). Patients are randomized to one of two treatment arms.

Arm I: Patients receive interleukin-2 (IL-2) subcutaneously (SC) twice daily on days 1 and 2 of weeks 1 and 3 and days 1-5 of weeks 2 and 4. Patients also receive histamine dihydrochloride SC over 10-30 minutes on days 1-5 of weeks 1-4.
Arm II: Patients receive IL-2 as in arm I. In both arms, treatment repeats every 6 weeks for at least 8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 3 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 224 patients (112 per treatment arm) will be accrued for this study.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Phase III, Multi-Center Controlled Trial With Stratified Randomization Comparing The Efficacy Of Interleukin-2 (IL-2) Plus Histamine Dihydrochloride (HDC) Versus IL-2 Alone To Increase The Duration Of Survival In Patients With AJCC Stage IV Malignant Melanoma With Hepatic Metastasis

Study Start Date :

Sep 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed stage IV melanoma
Must have radiological evidence of lesions in liver (target or non-target)
At least 1 measurable lesion outside previously irradiated field
At least 20 mm by contrast-enhanced CT scan, MRI, medical photography, or physical exam OR at least 10 mm by spiral CT scan
No prior or concurrent clinical and/or objective evidence of brain metastasis

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

WHO 0-1

Life expectancy:

At least 3 months

Hematopoietic:

Hemoglobin at least 9.5 g/dL
WBC at least 3,000/mm^3
Granulocyte count at least 2,000/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin no greater than 2 times upper limit of normal (ULN)
AST and ALT no greater than 4 times ULN
Alkaline phosphatase no greater than 4 times ULN
Hepatitis B and C negative

Renal:

Creatinine no greater than 1.7 mg/dL
Calcium no greater than 11.5 mg/dL

Cardiovascular:

No abnormal thallium stress test
No acute myocardial infarction within the past year
No New York Heart Association class III or IV heart disease

Pulmonary:

No asthma requiring active treatment within the past 5 years
Oxygen saturation by pulse oximeter at least 90% unless FEV_1 is greater than 2 L or at least 75% predicted

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
Concurrent medically-controlled (except with glyburide) or diet-controlled diabetes is allowed
Concurrent medically-controlled thyroid dysfunction is allowed
No other active malignancy within the past 5 years except carcinoma in situ of the cervix or localized squamous cell or basal cell skin cancer
No serious non-malignant medical conditions, including psychiatric disability, that would preclude study compliance
No active autoimmune disease (e.g., lupus, inflammatory bowel disease, or psoriasis)
No active peptic and/or esophageal ulcer disease
No hypersensitivity to histamine products or urticaria
No active IV drug abuse

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior immunotherapy with high-dose IV interleukin-2 (IL-2)
No prior combination immunotherapy with chemotherapy
At least 1 year since prior low-dose adjuvant IL-2 as part of vaccine therapy or as therapy for stage II or III melanoma

Chemotherapy:

See Biologic therapy

Endocrine therapy:

No chronic systemic glucocorticoid steroids
Asthma inhalers, topical creams, or intra-articular injections allowed
Hormonal therapy for non-melanoma-related conditions allowed

Radiotherapy:

See Disease Characteristics
Concurrent radiotherapy as palliative therapy for isolated non-target lesions (e.g., bone lesions) allowed

Surgery:

Not specified

Other:

At least 4 weeks since prior therapy directed at malignancy
At least 4 weeks since prior investigational medications or therapies
At least 2 weeks since prior parenteral antioxidants and/or vitamins
At least 2 weeks since prior antibiotics for active illness
At least 2 weeks since prior H2 antagonists, beta-blockers, antihypertensives, antimalarials, antitrypanosomals, neuromuscular-blocking agents, tricyclic antidepressants, or alprazolam
At least 24 hours since prior antihistamines
No prior enrollment in any Maxim Pharmaceuticals investigational trials
No concurrent anticonvulsant therapy for seizure disorder
No other concurrent investigational drug
No concurrent H2 antagonists, tricyclic antidepressants, alprazolam, beta- blockers, antihypertensives, antitrypanosomals, antimalarials, or monoamine oxidase inhibitors
No concurrent inhibitors of diamine oxidase, monoamine oxidase, or histamine N-methyltransferase
No concurrent antihistamines

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John Wayne Cancer Institute at Saint John's Health Center	Santa Monica	California	United States	90404
2	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado	United States	80010
3	Moffitt Clinic at Tampa General Hospital	Tampa	Florida	United States	33612
4	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
5	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
6	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
7	Melanoma Center of St. Louis, Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
8	Comprehensive Cancer Center at Our Lady of Mercy Medical Center	Bronx	New York	United States	10466
9	Beth Israel Medical Center	New York	New York	United States	10003
10	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
11	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15213-3489
12	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
13	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec	Canada	G1R 2J6
14	Charite - Universitaetsmedizin Berlin	Berlin		Germany	D-12200
15	Universitatsklinik - Saarland	Homburg/Saar		Germany	D-66421
16	Kiel Universitatshautklinik	Kiel		Germany	DOH-24105
17	Klinische Kooperationseinheit fur Dermatoonkologie (DFKZ)	Mannheim		Germany	68135
18	Klinikum Rechts Der Isar/Technische Universitaet Muenchen	Munich		Germany	D-81675
19	Royal Marsden Hospital - Sutton	London	England	United Kingdom	SW3 6JJ