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A Randomized Pilot Phase II Trial of Adjuvant Immunization With G250 Peptide andThree Different Dose Levels of IL-2 Following Surgical Resection of Locally Advanced or Metastatic Renal Cell Carcinoma

Phase 2
18 Years
Not Enrolling
Metastatic Renal Cell Carcinoma

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Trial Information

A Randomized Pilot Phase II Trial of Adjuvant Immunization With G250 Peptide andThree Different Dose Levels of IL-2 Following Surgical Resection of Locally Advanced or Metastatic Renal Cell Carcinoma

Renal cell carcinoma is a chemotherapy and radiotherapy resistant neoplasm that has a poor
prognosis. Immunotherapy with the biologic agent IL-2 consistently produces a response rate
of 10-15 %. Currently, for patients with locally advanced disease or patients with solitary
metastases, the only treatment modality with a curative potential is surgical resection.
There is presently no approved agent for use as adjuvant therapy after surgical resection to
decrease the risk of recurrence. Peptide-based vaccine approaches offer an attractive
treatment option.

The high prevalence of G250 in RCC, the definition of an HLA-A2-restricted epitope (the most
common HLA type), and its immunogenicity makes it the most attractive candidate for
peptide-based vaccine approaches in RCC therapy. The promising preclinical and clinical
evidence provides the rationale for the use of IL-2 to potentiate the antitumor effects of
cancer vaccines.

There is presently no conclusive data on the best dose of IL-2 to use as an adjuvant to
cancer vaccines. One paradoxical finding in preclinical and clinical trials is that despite
the enhancement in the antitumor effects of cancer vaccines, the number of antigen-specific
CTL is not increased when IL-2 is given with a cancer vaccine 35]. In contrast, patients
treated with peptide vaccines (without IL-2) in some melanoma trials had evidence of high
levels of antigen-specific CTL, with no tumor regression observed 36]. Some possible
explanations include capillary leak from high dose IL-2 resulting in CTL leaving the
circulation and the possibility that high dose IL-2 decreases efficient T-cell priming. A
more recent explanation has been proposed through advances in the mechanism of 1-cell
activation. As their level of activation increases, T-cells become more susceptible to
apoptosis. This phenomenon is known as activation-induced cell death (AICD) IL-2 may then
have a role in the amplification and downregulation of the immune response. High dose IL-2
may help in augmenting the increase in the activation of CTL, but this may lead to increase
their susceptibility to AJCD. The evidence in animal models that low doses of IL-2 were
sufficient in increasing the potency of DC-based immunizations provides the rational for our

In our current study, the lowest dose of IL-2 (1 x 106 IU) is similar to the doses used by
Yee et al. in their adoptive I cell therapy. This dose has been shown to expand and maintain
CTLs in both preclinical and clinical models. The highest dose (11 x 106 IU) was chosen
based on the expected toxicities from higher doses of IL-2 and our experience with this dose
as a single agent in RCC.

Our hypothesis is that immunization with G250/Montanide/GM-CSF plus IL-2 can lead to an
expansion of G250-specific CTL and result in killing of 0250 expressing micrometastatic RCC.
We propose a dose finding study of escalating low doses of IL 2 (subcutaneous), since no
prior study has specifically evaluated the use of low dose IL-2 as a cytokine adjuvant and
attempted to establish a correlation between dose and immunolgic response.

Inclusion Criteria:

- Patients must express HLA-A2

- Patients must have histologically or cytologically proven renal cell carcinoma that
expresses G250 by IHC

- Patients must have completely resected disease without any evidence of residual local
or metastatic disease

- Patients with resected locally advanced disease

- Patients with metastatic disease(including synchronous metastatic site)

- Patients with solitary metachronous metastatic disease

- Age >/=18 years

- ECOG performance status 0-1

- Patients must have normal organ and marrow function

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy, radiotherapy, or an experimental
(investigational) agent prior to starting treatment. Prior biologic therapy (IL-2 or
interferon) is allowed only if it precedes a curative surgical therapy.

- Patients may not have received a previous G250 vaccine.

- Patients with residual metastatic disease following surgical resection are excluded
from this clinical trial.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to G250, Montanide ISA-5 1, OM-CSF, or IL-2.

- Patients must not have autoimmune disorders (SLE, Rheumatoid Arthritis), conditions
of immunosuppression (such as HIV), or treatment with immunosuppressive drugs
(including oral steroids, continuous use of topical steroids, steroid inhalers).
Replacement doses of steroids for patients with adrenal insufficiency are allowed.

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, active GI bleeding, inflammatory bowel disease or psychiatric
illness/social situations that would limit compliance with study requirements.

- Pregnant or breast-feeding women

- HIV-positive patients

- Patients with a currently active second malignancy other than non-melanoma skin
cancer or carcinoma in situ of the cervix are not to be registered.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine whether immunization with G250 peptide/Montanide/GM-CSF plus IL-2 elicits a specific CTL response as assessed by ELISPOT.

Principal Investigator

Walter Stadler, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago


United States: Food and Drug Administration

Study ID:




Start Date:

October 2003

Completion Date:

March 2007

Related Keywords:

  • Metastatic Renal Cell Carcinoma
  • Metastatic Renal Cell Carcinoma
  • Carcinoma
  • Carcinoma, Renal Cell



The University of ChicagoChicago, Illinois  60637