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

Alternate Title

Vaccine Therapy in Treating Patients With Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed over 18 NCI MUSC-6124 NCI-T95-0044, T95-0044

Objectives

I.  Determine tolerance and side effects of repeated vaccinations with 
recombinant vaccinia virus that expresses the human carcinoembryonic antigen 
gene (rV-CEA) followed by repeated CEA peptide injection in patients with 
malignant solid tumors.

II.  Determine the optimal biologic dose for CEA peptide injection preceded by 
rV-CEA vaccination as determined by demonstration of humoral and/or cellular 
immune response in the majority of patients per cohort.

III.  Assess any evidence of antitumor activity in patients receiving the 
treatment.

Entry Criteria

Disease Characteristics:

Histologically confirmed adenocarcinoma of the gastrointestinal tract, breast, 
or lung 

Elevated serum CEA (at least 10 ng/mL) and/or tumor tissue positive for CEA on
immunohistochemical staining and tissue typing positive for HLA-A2

Unresectable and/or incurable tumor

For colorectal or breast cancer:
 Tumor progression after at least 1 prior chemotherapy regimen for advanced
  disease 

For pancreatic, gastric, or non-small cell lung cancer:
  Prior chemotherapy permitted but not required

No prior or active CNS metastases  

Prior/Concurrent Therapy:

Biologic therapy:
 Must have received prior vaccinia (for smallpox immunization)
 At least 3 days since antibiotics 
 No concurrent biologic therapy

Chemotherapy:
 No restriction on amount of prior chemotherapy
 At least 4 weeks since chemotherapy
 At least 6 weeks since nitrosoureas or mitomycin
 Recovered from all acute toxic effects
 At least 1 prior chemotherapy regimen for advanced disease required for
  colorectal and breast cancer patients
 No concurrent chemotherapy

Endocrine therapy:
 No concurrent steroid use

Radiotherapy:
 No prior radiation to more than 50% of nodal groups
 At least 4 weeks since radiation therapy
 Recovered from all acute toxic effects
 No concurrent radiotherapy

Surgery:
 No prior splenectomy
 At least 4 weeks since any surgery
 Must have recovered from surgery (surgical scars must be healed) 

Patient Characteristics:

Age:
 Over 18

Performance status:
 ECOG 0-1

Life expectancy:
 6-12 months

Hematopoietic:
 Absolute granulocyte count greater than 2,000/mm3
 Platelet count greater than 100,000/mm3
 Hemoglobin greater than 9.0 g/dL

Hepatic:
 Bilirubin less than 1.6 mg/dL
 AST and ALT less than 4 times normal

Renal:
 Creatinine less than 1.6 mg/dL

Other:
 No known history of allergy to eggs
 Must have normal immunologic testing as defined by normal delayed type
  hypersensitivity skin testing and normal CD4:CD8 ratio
 No known allergy or untoward reaction to prior vaccination with vaccinia
  virus
 Not HIV positive
 No other malignancy unless previous tumor was treated with curative intent
  and patient has been in remission for at least 2 years
 No altered immune function including:  
  Eczema (either prior or active)
  Atopic dermatitis
  Autoimmune disease (autoimmune neutropenia, thrombocytopenia, or hemolytic
   anemia; systemic lupus erythematosus; Sjogren syndrome; scleroderma;
   myasthenia gravis; Goodpasture's syndrome; Addison's disease; Hashimoto's
   thyroiditis; or active Grave's disease)
 No serious intercurrent illness
 No active infections requiring ongoing antibiotics 
 No inflammatory bowel disease
 No Crohn's disease
 No ulcerative colitis
 No active diverticulitis 
 No active cases of extensive psoriasis, severe acneiform rash, impetigo,
  varicella zoster, burns, or other traumatic or pruritic skin condition until
  condition is treated and resolved 
 Must be able to avoid contact with children less than 3 years of age,
  pregnant women, individuals with eczema or skin conditions described above,
  and immune suppressed individuals for at least 2 weeks after each
  vaccination
 No history of seizures, encephalitis, or multiple sclerosis
 Not pregnant or nursing
 Negative pregnancy test
 Adequate contraception required of all fertile patients

Expected Enrollment

A total of 16-48 patients will be accrued for this study.

Outline

All patients receive recombinant vaccinia CEA (rV-CEA) administered 
intradermally and CEA peptide vaccination administered subcutaneously.  
Rotation of injection sites are from deltoids, to thighs, to abdomen.  A 
combined total of 5 injections of rV-CEA and CEA peptide are possible so that 
no more than 2 injections occur at any area over a 5 month period.

A cohort of 3 patients are first treated as a dose level and must be evaluable 
for toxic effects for 2 weeks after the first treatment before entry of 
patients at the next higher dose level.

The maximum tolerated dose is defined at the dose level that is associated 
with no more than 1 instance of grade 3 or 4 toxicity among 3-6 patients 
treated.

Patients are followed weekly until day 28 after the final dose, and then 
monthly until disease progression or until initiation of any new form of 
therapy for the cancer.

Trial Contact Information

Trial Lead Organizations

Hollings Cancer Center at Medical University of South Carolina

David Cole, MD, Protocol chair		Ph: 843-792-4638 Email: coledj@musc.edu