Clinical trial NCT00019110: Vaccine Therapy in Treating Patients With Advanced or Recurrent Cancer
Official title: VACCINE THERAPY AND DETECTION OF IMMUNOLOGIC RESPONSES WITH HUMAN PAPILLOMAVIRUS 16 E6 AND E7 PEPTIDES IN PATIENTS WITH METASTATIC OR LOCALLY ADVANCED CERVICAL CANCER
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anal Cancer
Cervical Cancer
Esophageal Cancer
Head and Neck Cancer
Penile Cancer
Vulvar Cancer
Keywords: stage IV anal cancer
recurrent anal cancer
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer
stage IIIA anal cancer
stage IIIB anal cancer
recurrent esophageal cancer
stage III cervical cancer
stage IV cervical cancer
recurrent cervical cancer
stage III vulvar cancer
stage IVB vulvar cancer
recurrent vulvar cancer
stage III penile cancer
stage IV penile cancer
recurrent penile cancer
recurrent metastatic squamous neck cancer with occult primary
metastatic squamous neck cancer with occult primary squamous cell carcinoma
stage III squamous cell carcinoma of the lip and oral cavity
stage III basal cell carcinoma of the lip
stage III verrucous carcinoma of the oral cavity
stage III mucoepidermoid carcinoma of the oral cavity
stage III adenoid cystic carcinoma of the oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV basal cell carcinoma of the lip
stage IV verrucous carcinoma of the oral cavity
stage IV mucoepidermoid carcinoma of the oral cavity
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent basal cell carcinoma of the lip
recurrent verrucous carcinoma of the oral cavity
recurrent mucoepidermoid carcinoma of the oral cavity
recurrent adenoid cystic carcinoma of the oral cavity
stage III squamous cell carcinoma of the oropharynx
stage III lymphoepithelioma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
stage IV lymphoepithelioma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
recurrent lymphoepithelioma of the oropharynx
stage III squamous cell carcinoma of the nasopharynx
stage III lymphoepithelioma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
stage IV lymphoepithelioma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
recurrent lymphoepithelioma of the nasopharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage III verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
recurrent squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage III inverted papilloma of the paranasal sinus and nasal cavity
stage III midline lethal granuloma of the paranasal sinus and nasal cavity
stage III esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV inverted papilloma of the paranasal sinus and nasal cavity
stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent inverted papilloma of the paranasal sinus and nasal cavity
recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent salivary gland cancer
stage IV salivary gland cancer
stage III salivary gland cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines made from certain human papillomaviruses may be able to help the body to kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of human papillomavirus vaccine therapy in treating patients who have advanced or recurrent cancer of the cervix, vagina, penis, anus, esophagus, or head and neck.

Detailed description: OBJECTIVES:

* Determine whether endogenous cellular immunity to the viral oncoproteins human papilloma virus 16 (HPV16) E6 and E7 is present in patients with advanced or recurrent carcinoma of the cervix or other carcinomas that carry HPV16.
* Determine whether vaccination with antigen-presenting cells pulsed with synthetic peptide corresponding to the tumor's HPV16 E6 or E7 peptide can induce or boost patient cellular immunity to that particular peptide.
* Determine the type and characteristics of the cellular immunity generated in patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.
* Determine the tumor response in patients treated with this regimen.
* Determine whether in vivo T cells generated specifically against HPV16 E6 or E7 peptide can be cloned and expanded in vitro against the corresponding peptide.

OUTLINE: Patients are stratified according to disease category as defined by the following:

* Stratum A: Stage III cervical cancer not previously treated with appropriate radiotherapy; stage IV or recurrent cervical cancer; or other advanced tumors that harbor human papilloma virus 16 (HPV16) such as anogenital, esophageal, or head and neck cancers.
* Stratum B: Stage III cervical cancer previously treated with standard therapy with no evidence of residual disease. Vaccination in this group is given as adjuvant therapy.

Patients are assigned to receive HPV E6 or E7 peptide by the principal investigator. Peripheral blood mononuclear cells (PBMC) (antigen presenting cells) are harvested and treated in vitro with sargramostim (GM-CSF) and pulsed with HPV16 E6 or E7. Patients receive vaccination with HPV16 E6 or E7 pulsed PBMC IV over 1-2 minutes during weeks 1, 3, 7, and 11 for a total of 4 vaccinations. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) continue treatment for a maximum of 1 year past CR.

Patients are followed at 1 month.

PROJECTED ACCRUAL: A total of 40-46 patients (at least 28 patients for stratum A and 12 for stratum B) will be accrued for this study within 1-2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven stage III, IV, or recurrent carcinoma of the cervix or other tumor that carries human papilloma virus 16 (HPV16) such as other anogenital (vulvar, penile, and anal), esophageal, and head and neck cancers
* HLA-A2.1 positive
* Patients with tumors other than cervical cancer must have no other therapeutic options
* Fresh tissue or paraffin block available for HPV genome detection and typing (optional for cervical cancer)
* No history of CNS metastases

PATIENT CHARACTERISTICS:

Age:

* Over 18

Performance status:

* ECOG 0-1

Life expectancy:

* More than 3 months

Hematopoietic:

* WBC at least 2,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 2.0 mg/dL
* SGPT no greater than 4 times normal

Renal:

* Creatinine no greater than 2.0 mg/dL

Cardiovascular:

* No myocardial infarction within the past 6 months
* No New York Heart Association class III or IV heart disease

Immunologic:

* No autoimmune disease, e.g.:

  * Systemic lupus erythematosus
  * Multiple sclerosis
  * Ankylosing spondylitis
  * HIV negative
* Responsive to 1 of the following skin test antigens:

  * Mumps Trichophyton
  * Candida Tetanus

Other:

* No active infection requiring antibiotics
* No weight loss greater than 20% within the past 6 months
* No other active malignancy except basal cell skin cancer
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 4 weeks since prior immunotherapy and recovered

Chemotherapy:

* At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:

* At least 4 weeks since prior steroids and recovered

Radiotherapy:

* At least 4 weeks since prior radiotherapy and recovered

Surgery:

* Not specified

Other:

* Recovered from the toxic effects of prior therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Bethesda
country: United States
facility: Center for Cancer Research
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
Study officials:
affiliation: National Cancer Institute (NCI)
name: Barry L. Gause, MD
role: STUDY_CHAIR
References: