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

Alternate Title

Retinoid in Treating Patients With Advanced or Recurrent Non-small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Closed	18 and over	Pharmaceutical / Industry	LIGAND-L1069-20 NCI-V96-1050

Objectives

I.  Compare the progression-free interval following treatment with 
moderate-dose LGD1069 vs. high-dose LGD1069 vs. placebo in patients with stage 
IIIB/IV or recurrent non-small cell lung cancer that is stable or responding 
following combination chemotherapy with a platinum compound plus a taxane, 
etoposide, or a vinca alkaloid.

II.  Evaluate the safety and tolerability of LGD1069 in these patients.

III.  Document objective antitumor responses to LGD1069 in patients with 
measurable or evaluable disease.

IV.  Compare patient survival and quality of life in these three treatment 
groups.

Entry Criteria

Disease Characteristics:

Histologically confirmed, incurable non-small cell lung cancer in one of the
following categories:
  Stage IIIB with pleural effusion (T4, any N, M0)
  Stage IV (any T, any N, M1)
  Recurrent after curative resection or primary radiotherapy

Stable or responding disease following prior platinum-based combination
chemotherapy 
  No more than 1 prior chemotherapy regimen for advanced disease 
  4-6 cycles (equivalent to 12-24 weeks) of treatment
  No more than 21-35 days since completion of chemotherapy
  No subsequent disease progression

No CNS metastases unless radiographically stable or improved after whole brain
radiation and with evidence of neurologic improvement or normalization

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 At least 6 months since adjuvant chemotherapy
 See Disease Characteristics

Endocrine therapy:
 Not specified

Radiotherapy:
 See Disease Characteristics

Surgery:
 See Disease Characteristics

Other:
 At least 1 month since prior therapeutic retinoids 
  No prior therapeutic retinoids for non-small cell lung cancer
 At least 1 month since prior investigational agents
 No concurrent drugs that significantly alter hepatic or renal metabolism
  unless dose stable
 No concurrent vitamin A in excess of 15,000 IU/day

Patient Characteristics:

Age:
  18 and over

Performance status:
  ECOG 0-2

Life expectancy:
  At least 3 months

Hematopoietic:
  WBC at least 3,000/mm3
  Absolute neutrophil count at least 1,500/mm3
  Platelet count at least 100,000/mm3

Hepatic:
  Bilirubin no greater than 1.5 times normal
  AST/ALT no greater than 2.5 times normal
  PT and PTT normal
  Triglycerides (fasting) no greater than 800 mg/dL

Renal:
  Creatinine less than 2 times normal OR
  Creatinine clearance greater than 40 mL/min

Other:
  No serious concurrent medical illness
  No second malignancy within 5 years except nonmelanomatous skin cancer
  No pregnant or nursing women
     Negative pregnancy test required of fertile women within 7 days prior to
     entry
  Effective contraception (including abstinence) required of fertile patients
     for 4 weeks prior to, during, and for at least 3 months after treatment

Expected Enrollment

A total of 90 patients will be entered in the Phase II portion of this 
multicenter study.

Outline

This is a randomized, double-blind study.  Patients are stratified by 
participating institution.

Patients are randomly assigned to receive daily oral treatment with high-dose 
LGD1069, moderate-dose LGD1069, or placebo.  Patients in the placebo group are 
evenly divided to receive approximately 7 or 14 capsules per day.

Treatment in all groups continues until disease progression or unacceptable 
toxicity intervenes.  Upon disease progression, patients may receive 
alternative therapy at the investigator's discretion.

No concurrent radiotherapy, hormonal therapy (including progestational agents 
for appetite stimulation), chemotherapy, immunotherapy, or investigational 
therapies.  Chronic low-dose replacement hormone therapy or low-dose 
corticosteroids for noncancer-related conditions are allowed.

Patients are followed every 2 weeks for 1 month, then every 4 weeks during 
treatment, at 4 weeks after the last dose, then for survival.

Trial Contact Information

Trial Lead Organizations

Ligand Pharmaceuticals, Incorporated

John Tucker, Protocol chair		Ph: 858-550-7786