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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


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Melanoma (Skin), Metastatic Cancer

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Trial Information

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


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

John A. Glaspy, MD, MPH

Investigator Role:

Study Chair

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000069365

NCT ID:

NCT00039234

Start Date:

September 2002

Completion Date:

Related Keywords:

  • Melanoma (Skin)
  • Metastatic Cancer
  • stage IV melanoma
  • recurrent melanoma
  • liver metastases
  • Melanoma
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Chicago Cancer Research CenterChicago, Illinois  60637
Beth Israel Medical CenterNew York, New York  10003
University of Colorado Cancer Center at University of Colorado Health Sciences CenterDenver, Colorado  80010
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
Hillman Cancer Center at University of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania  15236
James Graham Brown Cancer Center at University of LouisvilleLouisville, Kentucky  40202
John Wayne Cancer Institute at Saint John's Health CenterSanta Monica, California  90404
Comprehensive Cancer Center at Our Lady of Mercy Medical CenterBronx, New York  10466
Moffitt Clinic at Tampa General HospitalTampa, Florida  33612-9497
Melanoma Center of St. Louis, Missouri Baptist Medical CenterSaint Louis, Missouri  63131