Know Cancer

or
forgot password

A Phase 1 Open Label, Dose Escalation Study to Evaluate the Effect of Four Doses of MAGE-A3/HPV 16 Trojan Peptides 0001 and 0002 Administered Subcutaneously in Combination With Montanide and GM-CSF on Immunological Response, Safety, Tolerability, and Preliminary Efficacy in Patients With Squamous Cell Carcinoma of the Head and Neck


Phase 1
18 Years
80 Years
Open (Enrolling)
Both
Squamous Cell Carcinoma of the Head and Neck

Thank you

Trial Information

A Phase 1 Open Label, Dose Escalation Study to Evaluate the Effect of Four Doses of MAGE-A3/HPV 16 Trojan Peptides 0001 and 0002 Administered Subcutaneously in Combination With Montanide and GM-CSF on Immunological Response, Safety, Tolerability, and Preliminary Efficacy in Patients With Squamous Cell Carcinoma of the Head and Neck


Squamous Cell Carcinoma of the Head and Neck affects 43,000 individuals in the United States
annually with an estimated overall survival rate of 50%. In order to improve both the
survival rate and quality of life for patients who develop unresectable disease recurrence,
new therapeutic alternatives are mandated. One potential treatment alternative for this
patient population is the use of peptide-based immunotherapy. Despite the success fo
preclinical studies using peptide vaccines, therapeutic responses in patients have been
sporadic. The reasons for failure are multifactorial and include problems with patient
selection, a limited number of antigenic targets, and an inability to correlate immunologic
response with therapeutic efficacy. Specifically, patients with disseminated SCCHN have
defects in antigen processing, presentation and effector mechanisms that limit their ability
to respond to T cell based immunotherapy. Additionally, a paucity of antigenic peptide
epitopes are defined for SCCHN, and immunologic monitoring does not correlate well with
clinical response.

Recently several investigators, including our research team, have identified a high
prevalence of MAGE-A3 and HPV 16 on SCCHN, and characterized several putative cytolytic and
helper epitopes. Additionally, we have defined a novel method to enhance the immune response
to therapeutic peptide vaccines using Trojan complexes composed of CD4 and CD8 T-cell
epitopes, connected by furin cleavable linkers.

In order to define the feasibility and safety of these agents in combination with GM-CSF and
montanide ISA 51 for the immunotherapy of SCCHN, in this proposed trial, we will screen
patients for immunologic competence based on specific eligibility criteria including both
antigen and HLA-A2 expression on tumors. In registered patients, we will test the ability of
two novel Trojan peptide complexes, composed of MAGE-A3 and human papilloma virus 16 (HPV
16) epitopes, to stimulate antigen-specific CD 4 and CD 8 T-cell responses. Finally, we will
correlate immunologic response with cell dose and the generation of both HPV 16 and MAGE-A3
antigen loss and HLA-A2 loss variants on tumors by evaluating patients for: 1) Changes in
tumor size by both physical measurement and CT plus PET measurement; 2) Determining what
proportions of individuals who achieve a complete response (CR), partial response (PR), or
have stable disease (SD); 3) Progression-free survival; 4) Survival. Successful completion
of this clinical trial will result in the development of a strong foundation for a Phase
II/III clinical trial using HPV 16 and MAGE-A3 Trojan peptides for the immunotherapy of
SCCHN.


Inclusion Criteria:



1. Age 18 or older

2. Biopsy proven progressive, recurrent (post-surgical, radiation therapy, chemotherapy,
combination therapy),or metastatic SCC of the head and neck which, in the judgment of
the attending physician, is incurable by standard treatment modalities, OR Biopsy
proven SCC which the patient is unwilling to have treated with surgery, chemotherapy
or radiation therapy

3. One or more of the following: -MAGE-A3 positive tumor -HPV 16 positive tumor.

4. Laboratory values obtained less than or equal to 30days prior to registration:
-Alkaline phosphatase less than or equal to 3x upper normal limit (UNL) -AST less
than or equal to 3x UNL -Creatinine less than or equal to 1.5 x UNL -Hemoglobin
greater than or equal to 9.0 g/dL -Albumin greater than or equal to 3 mg/dL

5. The subject must be capable of understanding the investigational nature, potential
risks and benefits of the study and capable of providing valid informed consent.

6. The subject must be willing to return to the University of Maryland Medical center
for treatment and study related follow up procedures including blood and tumor
collections and completion of imaging studies as required by the protocol.

7. ECOG performance status 0-2.

8. Tumor that is biopsy accessible and measurable. This includes, but is not limited to,
open biopsy, endoscopic biopsy, image guided biopsy, core biopsy and fine needle
aspiration.

EXCLUSION

1. Any of the following:

a. Known HIV infection, b. Other circumstances (i.e. concurrent use of systemic
immunosuppressants and immunocompromising condition) that in the opinion of the
physician renders the patient a poor candidate for this trial. c. Patients with ANY
malignant or metastatic SCC mass or lesion within the Central Nervous System (CNS).
(e.g. Intraparenchymal/ Brain, Intracordal / Spinal Canal, Bony masses or lesions
with extension into the CNS parenchyma) d. Patients with ANY malignant or metastatic
SCC mass or lesion or a volume of a mass or lesion in a location that in the judgment
of the investigator may significantly impair the health of or threaten the patients
life, should an Inflammatory Response occur.

2. Any of the following prior therapies: Chemotherapy less than or equal to 4 weeks
prior to registration Immunotherapy less than or equal to 4 weeks prior to
registration Biologic therapy less than or equal to 4 weeks prior to registration
Radiation therapy less than or equal to 4 weeks prior to registration

3. Any of the following: Pregnant women Nursing women unwilling to stop breastfeeding
Men or women of childbearing potential who are unwilling to employ adequate
contraception (condoms, diaphragm, birth control pills, injections, intrauterine
device [IUD], or abstinence, etc.) NOTE:This study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and
newborn are unknown.

4. Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
considered investigational (utilized for a non-FDA-approved indication and in the
context of a research investigation).

5. Either of the following: Other active cancer requiring therapy to control the disease
History of other malignancy (i.e. excluding disease under study) within 3 years
Exceptions to the above include: adequately treated basal cell or squamous cell skin
cancer, prostate cancer.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity: Maximum grade of each toxicity and percentage of patients experiencing toxicity.

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Martin J. Edelman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Maryland, Greenebaum Cancer Ctr

Authority:

United States: Food and Drug Administration

Study ID:

HP-00041372

NCT ID:

NCT00257738

Start Date:

November 2005

Completion Date:

December 2011

Related Keywords:

  • Squamous Cell Carcinoma of the Head and Neck
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

Name

Location

University of Maryland School of MedicineBaltimore, Maryland  21201-1619