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

Alternate Title

ISIS 3521 in Treating Patients With Advanced, Unresectable, or Metastatic Non-small Cell Lung Cancer or Unresectable or Metastatic Melanoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	Pharmaceutical / Industry	EORTC-16977 ISIS-EORTC-16977, NCT00003989

Objectives

I. Determine the complete and partial response rates and duration of response 
in patients with locally advanced, unresectable, or metastatic non-small cell 
lung cancer or unresectable or metastatic melanoma treated with ISIS 3521.

II. Determine safety of ISIS 3521 in these patients.

Entry Criteria

Disease Characteristics:

Histologically or cytologically proven melanoma that is unresectable and
regionally metastatic, or widely disseminated 
 
OR

Histologically or cytologically proven non-small cell lung cancer (NSCLC) that
is locally advanced, unresectable, or metastatic 
 Stage IIIA, IIIB, or IV
 Evidence of disease progression prior to study

At least 1 bidimensionally measurable lesion 
 The following are NOT considered measurable: previously irradiated lesions,
  ascites, pleural effusion, bone metastases, brain metastases, leptomeningeal
  disease, or an abdominal mass that can be palpated but not measured

Melanoma patients whose only manifestation of disease is 1 of the following
are NOT eligible:
 Lymphedema
 Pleural effusion
 Ascites
 CNS metastases
 Bone marrow infiltration 
 Osteoblastic bone lesions
 

Prior/Concurrent Therapy:

Biologic therapy:
 At least 4 weeks since prior immunotherapy (including interferon or
  interleukin-2) for melanoma patients
 No other concurrent anticancer immunotherapy 
 
Chemotherapy:
 No prior chemotherapy for melanoma patients except adjuvant or
  local chemotherapy (extracorporeal circulation) 
  At least 4 weeks since prior adjuvant or local chemotherapy if presence of
   measurable lesions outside the treated limb (6 months
   if no presence of measurable lesions outside the treated limb)
 No prior chemotherapy for NSCLC except platinum compounds used as
  radiosensitizer 
  At least 4 weeks since prior platinum compounds 
 No other concurrent anticancer chemotherapy

Endocrine therapy:
 Not specified 

Radiotherapy:
 At least 4 weeks since prior radiotherapy 
 Concurrent radiotherapy allowed for bone pain or other reasons
  No irradiation of all evaluable lesions
 
Surgery:
 See Disease Characteristics

Other:
 At least 4 weeks since other prior investigational drugs 
 No other concurrent investigational drugs
 No concurrent anticoagulants except heparin used to prevent occlusion
  of IV lines during week(s) off treatment
  

Patient Characteristics:

Age:
 18 and over

Performance status:
 WHO 0-2

Life expectancy:
 At least 3 months

Hematopoietic:
 Neutrophil count at least 1,500/mm3
 Platelet count at least 100,000/mm3
 No abnormal clotting tests

Hepatic:
 Bilirubin no greater than 2.0 mg/dL
 AST and ALT no greater than 2 times upper limit of normal (ULN) (5 times ULN
  if due to liver metastases)
 
Renal:
 Creatinine no greater than 1.6 mg/dL OR
 Creatinine clearance at least 60 mL/min
 Urinary protein less than 0.3 g/dL

Cardiovascular:
 No superior vena cava obstruction in NSCLC unless successfully treated at
  least 2 months prior to study

Other:
 No underlying disease state associated with active bleeding
 No prior or concurrent malignancies at other sites except adequately treated
  cone biopsied carcinoma in situ of the cervix uteri or basal cell or
  squamous cell skin cancer
 No nonmalignant systemic disease making patient poor risk for study
 No active uncontrolled infection
 Not pregnant or nursing 
 Negative pregnancy test
 Fertile patients must use effective contraception during and for 3 weeks
  after study

Expected Enrollment

A total of 28-50 patients (14-25 per stratum) will be accrued for this study.

Outline

This is a multicenter study.  Patients are stratified by disease type.  

Patients receive ISIS 3521 IV over 21 days followed by 7 days of rest.  
Courses repeat every 28 days in the absence of disease progression or 
unacceptable toxicity.  

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Shoshana Kaplan, MD, Protocol chair(Contact information may not be current)		Ph: 41-61-265-2525

Registry Information
Official Title		Phase II Trial with ISIS 3521/CGP 64128A in Patients with Malignant Melanoma and Non Small Cell Lung Cancer
Trial Start Date		1998-06-01
Registered in ClinicalTrials.gov		NCT00003989
Date Submitted to PDQ		1999-07-08
Information Last Verified		2000-05-01