Clinical trial NCT00098917: Vaccine Therapy in Treating Patients Who Are Undergoing Surgery for Stage IB, Stage II, or Stage IIIA Non-Small Cell Lung Cancer
Official title: A Phase I Clinical Trial of Mature Autologous Dendritic Cells Loaded With Irradiated Autologous Tumor Cells for the Treatment of Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lung Cancer
Keywords: stage I non-small cell lung cancer
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-12-09
Enrollment: 15
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 person's tumor cells and white blood cells may make the body build an effective immune response to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients who are undergoing surgery for stage IB, stage II, or stage IIIA non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the maximum tolerated dose of adjuvant autologous dendritic cells loaded with irradiated autologous tumor cells in patients with stage IB-IIIA non-small cell lung cancer undergoing resection.
* Determine the safety and tolerability of this vaccine in these patients.

Secondary

* Determine the feasibility of this vaccine in these patients.
* Determine vaccine-specific and antitumor immunity in patients treated with this vaccine.

OUTLINE: This is a dose-escalation study.

Patients undergo leukaphersis to isolate peripheral blood mononuclear cells (PBMC). PBMC are expanded ex vivo to generate monocyte-derived dendritic cells (DC). Autologous tumor cells are harvested and purified at the time of surgical resection. DC are then loaded with irradiated autologous tumor cells.

Within 4-8 weeks after surgical resection, patients receive autologous DC loaded with irradiated autologous tumor cells intradermally on approximately days 1, 30, and 60 in the absence of unacceptable toxicity.

Cohorts of 6-9 patients receive escalating doses of vaccine until the maximum tolerated dose (MTD) is determined. If 2 of 9 patients in the first cohort experience dose-limiting toxicity, that dose level is considered the MTD.

Patients are followed at approximately 1 and 4 months, and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study within 18 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of non-small cell lung cancer

  * Clinical stage IB-IIIA disease
* Candidate for surgical resection as primary treatment for tumor

  * Surgically resectable tumor ≥ 2.0 cm in diameter
* No brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Zubrod 0-1

Life expectancy

* Not specified

Hematopoietic

* Platelet count ≥ 100,000/mm\^3
* WBC ≥ 3,000/mm\^3
* Absolute neutrophil count ≥ 1,500/mm\^3
* Hematocrit ≥ 30%

Hepatic

* Hepatitis B surface antigen negative\*
* Hepatitis B core antigen negative\*
* Hepatitis C virus negative\*
* Bilirubin ≤ 2.0 mg/dL
* AST and ALT ≤ 2 times upper limit of normal NOTE: \*Screening performed only if liver enzymes are elevated

Renal

* Creatinine ≤ 2.2 mg/dL
* BUN ≤ 40 mg/dL

Pulmonary

* FEV_1 \> 2.0 L (pre-resection) OR
* Predicted post-resection FEV_1 \> 1.0 L
* No more than 2 chronic obstructive pulmonary disease exacerbations requiring \> 2 weeks of oral steroids and/or hospitalization within the past year

Immunologic

* Purified protein derivative (PPD) skin test negative
* HIV-1 and HIV-2 negative
* No acute infection, including any acute viral, bacterial, or fungal infection requiring specific therapy within the past 7 days
* No allergy to study agents
* No known autoimmune or collagen vascular disorder

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
* No underlying condition that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent anti-tumor necrosis factor agents

Chemotherapy

* Standard adjuvant chemotherapy for lung cancer allowed provided therapy is completed ≥ 30 days before administration of the first study vaccine
* No concurrent cyclophosphamide

Endocrine therapy

* No concurrent high-dose corticosteroids (e.g., \> 10 mg of prednisone)
* Concurrent corticosteroids for minor breathing exacerbations allowed provided patient receives ≤ 2 short courses (≤ 10 days per course) within a 45-day period
* No concurrent corticosteroids within 48 hours before or after study vaccine administration

Radiotherapy

* Standard adjuvant radiotherapy for lung cancer allowed provided therapy is completed ≥ 30 days before administration of the first study vaccine

Surgery

* No prior organ allograft

Other

* No concurrent antihistamines within 48 hours before or after study vaccine administration
* No concurrent cimetidine or other H2 blockers within 48 hours before or after study vaccine administration
* Concurrent antibiotics for minor infection allowed provided patient receives ≤ 2 short courses (≤ 10 days per course) within a 45-day period
* No concurrent cyclosporine
* No concurrent azathioprine
* No other concurrent drugs known to significantly alter immune function
* No concurrent cytotoxic therapy
* No concurrent participation in another clinical trial involving experimental therapy
* No other concurrent anticancer therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: Michael D. Roth, MD
role: PRINCIPAL_INVESTIGATOR
References: