Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Indomethacin Plus Biological Therapy in Treating Patients With Advanced Melanoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	Over 16	Other	STLMC-BRM-93004 NCI-V93-0295, NCT00002535

Objectives

I.  Determine whether indomethacin given prior to tumor removal can increase 
the number of tumor infiltrating lymphocytes (TIL) obtained from the tumor 
specimen of patients with advanced melanoma.

II.  Determine the efficacy of administering concurrent indomethacin to 
maximize immune effector cell function in situ during interleukin-2/TIL 
therapy in these patients.

III.  Determine the relationship between the phenotypic character of TIL 
(generated in culture from the patient's tumor) and the response to therapy.

IV.  Correlate the lytic activity or lymphokine production of TIL (generated 
in culture from the patient's tumor) with clinical response to therapy.

V.  Generate and use lymphokine-activated killer (LAK) cells in those patients 
who do not have TIL available for therapy and evaluate LAK cells in the same 
manner as TIL.

Entry Criteria

Disease Characteristics:

Histologically documented melanoma that is metastatic or
unresectable and unresponsive to conventional chemotherapy
and/or radiotherapy

Measurable or evaluable disease required
  Measurable disease defined as bidimensionally measurable
  lesion on physical exam, x-ray, or MRI

  Evaluable disease defined as:
     Unidimensionally measurable lesion on x-ray, scan, or
        photograph
     Disease assessable by serial chemistries, tumor markers,
        or nonspecific scans
     Disease assessable by functional manifestations (e.g.,
        change in performance status, 10% or greater change in
        weight)
     Previously irradiated lesion with subsequent disease
        progression documented
     Bone-only lesions may be considered evaluable (lytic
        lesion on x-ray or bone scan should be followed)

No metastases on CT or MRI involving more than 50% of the liver

No uncontrolled or untreated CNS metastases

Prior/Concurrent Therapy:

Biologic therapy:
  More than 4 weeks since immunotherapy

Chemotherapy:
  Prior anthracyclines allowed provided no symptomatic heart
     disease is present
  More than 4 weeks since chemotherapy (at least 2 weeks, with
     recovery, if disease progression is documented)
  More than 6 weeks since nitrosoureas, melphalan, or
     mitomycin

Endocrine therapy:
  More than 1 week since corticosteroids (except physiological
  doses for respiratory ailments or adrenal insufficiency)

Radiotherapy:
  More than 4 weeks since radiotherapy (at least 2 weeks, with
     recovery, if disease progression is documented)

Surgery:
  More than 3 weeks since major surgery (excluding surgery for
  tumor collection)

Patient Characteristics:

Age:
  Over 16

Performance status:
  ECOG 0 or 1

Life expectancy:
  At least 3 months

Hematopoietic:
  (unless tumor involvement of bone marrow or spleen is
     documented)
  WBC at least 3,500/mm3
  Absolute granulocyte count at least 1,500/mm3
  Platelet count at least 100,000/mm3
  Hemoglobin at least 11.5 g/dL
  No significant hematologic abnormalities

Hepatic:
  (unless tumor involvement of liver is documented)
  Bilirubin no greater than 1.6 mg/dL
  SGOT no greater than 150 U/L
  PT at least 1.5 times control
  PTT less than 1.5 times control

Renal:
  (unless tumor involvement of kidney is documented)
  Creatinine no greater than 2.0 mg/dL
  Creatinine clearance at least 50 mL/min 
  Calcium no greater than 12 mg/dL
   No symptomatic hypercalcemia

Cardiovascular:
  No myocardial infarction within 6 months
  No congestive heart failure
  No edema
  No hypotension or hypertension
  No coronary artery disease
  No history of arrhythmia
  No contraindication to the use of pressor agents

Pulmonary:
  FEV1 at least 65% of predicted

Other:
  No significant organ dysfunction
  No uncontrolled bacterial, viral, or fungal infection
  No active peptic or duodenal ulcer
  No psychiatric or seizure disorder
  No prior solid organ allograft
  HIV and hepatitis B surface antigen seronegative within 6
   months of study entry
  No second malignancy within 5 years except:
     Inactive nonmelanomatous skin cancer
     Carcinoma in situ of the cervix
  No other serious illness that would limit survival to less
     than 2 years
  Negative pregnancy test 

Expected Enrollment

Up to 30 patients will be accrued over 3 years.  If 0 of the first 10 
patients, no more than 1 of the first 15 patients, or no more than 2 of the 
first 20 patients respond, accrual will cease.

Outline

Patients with resectable tumors and with adequate generation of TIL are 
treated on Regimen A; those with unresectable tumors or insufficient TIL are 
treated on Regimen B.

The following acronyms are used:
  CTX     Cyclophosphamide, NSC-26271
  IL-2    Interleukin-2 (Cetus), NSC-373364
  LAK     Lymphokine-Activated Killer Cells
  TIL     Tumor Infiltrating Lymphocytes

Regimen A:  Prostaglandin Inhibition Therapy plus Biological Response Modifier 
Therapy.  Indomethacin; plus CTX; IL-2-activated TIL; IL-2.

Regimen B:  Prostaglandin Inhibition Therapy plus Biological Response Modifier 
Therapy.  Indomethacin; plus IL-2-activated LAK; IL-2.

Trial Contact Information

Trial Lead Organizations

Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center

John Hanson, MD, Protocol chair		Ph: 414-649-5818; 800-252-2990 Email: jphanson@cancerrx.com

Registry Information
Official Title		TUMOR INFILTRATING LYMPHOCYTE THERAPY FOR ADVANCED MELANOMA USING IMMUNOMODULATION, A PHASE II STUDY
Trial Start Date		1993-07-09
Registered in ClinicalTrials.gov		NCT00002535
Date Submitted to PDQ		1993-07-09
Information Last Verified		2000-08-01

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