Clinical trial NCT00019331: Vaccine Therapy Plus Biological Therapy in Treating Adults With Metastatic Solid Tumors
Official title: Vaccine Therapy With Tumor Specific Mutated Ras Peptides and IL-2 or GM-CSF for Adult Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Endometrial Cancer
Head and Neck Cancer
Liver Cancer
Lung Cancer
Melanoma (Skin)
Pancreatic Cancer
Testicular Germ Cell Tumor
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: stage IV colon cancer
recurrent non-small cell lung cancer
stage II pancreatic cancer
stage III pancreatic cancer
recurrent pancreatic cancer
recurrent colon cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer
advanced adult primary liver cancer
recurrent adult primary liver cancer
stage IV endometrial carcinoma
recurrent endometrial carcinoma
stage III malignant testicular germ cell tumor
recurrent malignant testicular germ cell tumor
stage IV papillary thyroid cancer
stage IV follicular thyroid cancer
thyroid gland medullary carcinoma
anaplastic thyroid cancer
recurrent thyroid cancer
stage IV melanoma
recurrent melanoma
stage IV non-small cell lung cancer
unspecified adult solid tumor, protocol specific
untreated metastatic squamous neck cancer with occult primary
recurrent metastatic squamous neck cancer with occult primary
adult primary hepatocellular carcinoma
pulmonary carcinoid tumor
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
stage IV adenoid cystic 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 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 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 IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the hypopharynx
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 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
insular thyroid cancer
recurrent salivary gland cancer
stage IV salivary gland cancer
stage IV pancreatic cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines made from a peptide may make the body build an immune response to kill tumor cells. Combining vaccine therapy with interleukin-2 and/or sargramostim may be a more effective treatment for solid tumors.

PURPOSE: Phase II trial to study the effectiveness of vaccine therapy plus interleukin-2 and/or sargramostim in treating adults who have metastatic solid tumors.

Detailed description: OBJECTIVES:

* Determine whether endogenous cellular immunity to a tumor-specific mutated ras protein is present in cancer patients.
* Determine whether vaccination with synthetic peptides corresponding to the tumor's ras mutation with DetoxPC adjuvant, interleukin-2 (IL-2), and/or sargramostim (GM-CSF) can induce or boost a patient's cellular immunity to that particular mutation.
* Determine the type and characteristics of the cellular immune response generated.
* Determine the tolerance to and toxicity spectrum of such peptides given with DetoxPC adjuvant along with IL-2 and/or GM-CSF.
* Correlate immune response with tumor response in patients treated with these regimens.

OUTLINE: Patients are assigned to one of three treatment groups.

* Group I (closed to accrual 6/4/01): Patients receive tumor-specific ras peptide vaccine with DetoxPC subcutaneously (SC) once every 5 weeks for 3 courses. Beginning 4 days after vaccination, patients receive interleukin-2 (IL-2) SC 5 days a week for 2 weeks.
* Group II (closed to accrual 6/4/01): Patients receive sargramostim (GM-CSF) SC daily beginning 1 day prior to the vaccination and continuing for 4 days. Patients receive the vaccination as in group I immediately followed by GM-CSF on day 2. Patients are vaccinated once every 4 weeks for 3 courses.
* Group III: Patients receive the vaccination and IL-2 as in group I and GM-CSF as in group II.

In all groups, patients receive up to 15 vaccinations in the absence of disease progression.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A maximum of 60 patients (20 per treatment group) will be accrued for this study within 2-4 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed solid tumors potentially expressing mutant ras, including colon, lung, pancreas, thyroid, endometrial, head and neck, testicular, hepatocellular, and melanoma
* Ras mutations must be one of the following point mutations at codon 12:

  * Glycine to cysteine
  * Glycine to aspartic acid
  * Glycine to valine
* Metastatic disease for which no known chemotherapy or radiotherapy would increase survival
* Tumor tissue must be available for determination of ras mutation
* No prior CNS metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

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
* SGOT/SGPT no greater than 4 times normal
* No hepatitis B or C infection

Renal:

* Creatinine no greater than 2.0 mg/dL

Cardiovascular:

* No active ischemic heart disease (New York Heart Association class III or IV)
* No myocardial infarction within the past 6 months
* No history of congestive heart failure, ventricular arrhythmias, or other arrhythmias requiring therapy

Immunologic:

* No prior allergy to eggs
* No prior autoimmune disease, including the following:

  * Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia
  * Systemic lupus erythematosus, Sjogren's syndrome, or scleroderma
  * Myasthenia gravis
  * Goodpasture syndrome
  * Addison's disease, Hashimoto's thyroiditis, or active Graves' disease

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative
* No other active malignancy except curatively treated carcinoma in situ of the cervix or basal cell skin cancer
* No active infection requiring antibiotics
* No medical condition that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 4 weeks since prior immunotherapy and recovered

Chemotherapy:

* See Disease Characteristics
* At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:

* At least 4 weeks since prior steroids and recovered

Radiotherapy:

* See Disease Characteristics
* At least 4 weeks since prior radiotherapy and recovered

Surgery:

* Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Barry L. Gause, MD
role: STUDY_CHAIR
References: