S0122: Combination Chemotherapy, Radiation Therapy, and Vaccine Therapy in Limited-Stage Small Cell Lung Cancer

SWOG Cancer Research Network

Status and phase: Terminated; Phase 2

Conditions: Lung Cancer

Treatments: Biological: monoclonal antibody GD2 anti-idiotype vaccine; Biological: monoclonal antibody 11D10 anti-idiotype vaccine; Radiation: radiation therapy; Drug: cisplatin; Drug: etoposide

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00045617

CDR0000256922

S0122 (Other Identifier)

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high energy x-rays to damage tumor cells. Vaccines may make the body build an immune response to kill tumor cells. Combining chemotherapy and radiation therapy with vaccine therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy and radiation therapy with vaccine therapy in treating patients who have limited-stage small cell lung cancer.

Full description

OBJECTIVES:

• Determine the efficacy of cisplatin, etoposide, and thoracic radiotherapy followed by cisplatin, etoposide, monoclonal antibody 11D10 anti-idiotype vaccine (TriAb), and monoclonal antibody GD2 anti-idiotype vaccine (TriGem), in terms of overall and progression-free survival of patients with limited stage small cell lung cancer.
• Determine the immune response to each of the 2 anti-idiotype vaccines when used in this regimen in these patients.
• Determine the qualitative and quantitative toxicity of this regimen in these patients.
• Determine the response rates (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with this regimen.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Thoracic radiotherapy is administered 5 days a week, beginning on day 1 of chemotherapy, for 5 weeks. Patients then undergo radiotherapy boost for 1.5 weeks.

Patients with stable disease or at least partial response proceed to consolidation therapy.

• Consolidation therapy (begins within 3-5 weeks of the last dose of induction chemotherapy or radiotherapy): Patients receive cisplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3 of weeks 11 and 14. Patients also receive monoclonal antibody 11D10 anti-idiotype vaccine (TriAb) and monoclonal antibody GD2 anti-idiotype vaccine (TriGem) intradermally on day 1 of weeks 11, 13, 15, and 17 (4 injections) and then monthly subcutaneously for 2 years. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients who achieve complete response after consolidation chemotherapy undergo cranial radiotherapy 5 days a week for 3 weeks.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study within 18 months.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed limited stage small cell lung cancer (SCLC)
• Evidence of disease by CT scan of the chest
• Measurable or evaluable disease outside of area of prior surgical resection
• No malignant pericardial or pleural effusions (cytologically positive effusions or exudative effusions not attributable to other etiologies)
• No CNS disease by chest CT scan or MRI

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Not specified

Renal

• Creatinine no greater than upper limit of normal OR
• Creatinine clearance at least 60 mL/min

Other

• No prior hypersensitivity or contraindication to monoclonal antibody 11D10 anti-idiotype vaccine (TriAb), monoclonal antibody GD2 anti-idiotype vaccine (TriGem), or aluminum hydroxide
• No known sensitivity to rodent proteins (i.e., anti-OKT-3, ONCOSCINT scan)
• No grade 1 or greater symptomatic sensory neuropathy
• No other malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer in complete remission, or any other cancer for which patient has been disease free for 5 years
• If significant clinical hearing loss already present, must accept risk of further hearing loss
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic therapy for SCLC
• No prior TriAb or TriGem
• No prior murine antibodies
• No prior mouse proteins
• At least 30 days since prior immunotherapy
• At least 30 days since any prior immunization

Chemotherapy

• No prior systemic chemotherapy for SCLC
• No concurrent cyclophosphamide or methotrexate

Endocrine therapy

• At least 30 days since prior systemic corticosteroids
• No concurrent systemic corticosteroids (except as an antiemetic)

Radiotherapy

• No prior radiotherapy to the thorax or neck region
• No concurrent intensity modulated radiotherapy

Surgery

• See Disease Characteristics
• At least 2 weeks since prior thoracic or other major surgery and recovered

Other

• At least 30 days since prior investigational agents or devices
• No other concurrent investigational agents
• No other concurrent immunosuppressants (e.g., cyclosporine)
• No concurrent chronic systemic antihistamines
• No concurrent amifostine

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

cisplatin and etoposide followed by vaccine

Experimental group

Description:

standard chemotherapy with cisplatin and etoposide followed by cisplans and etoposide with an anti-idiotype monoclonal antibody vaccine

Treatment:

Drug: cisplatin

Biological: monoclonal antibody GD2 anti-idiotype vaccine

Drug: etoposide

Biological: monoclonal antibody 11D10 anti-idiotype vaccine

Radiation: radiation therapy