Know Cancer

or
forgot password

Identification of a Gene Expression Signature Profile for Panitumumab Sensitivity in Untreated Locally Advanced Squamous Cell Cancer of the Head and Neck (SCCHN)


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Squamous Cell Carcinoma of the Head and Neck

Thank you

Trial Information

Identification of a Gene Expression Signature Profile for Panitumumab Sensitivity in Untreated Locally Advanced Squamous Cell Cancer of the Head and Neck (SCCHN)


This trial will attempt to identify a gene expression signature profile biomarker for
panitumumab sensitivity in locally advanced, untreated SCCHN. SCCHN expresses or over
expresses EGFR in >90% of tumors. Panitumumab is a fully human IgG2 monoclonal antibody
approved for the treatment of epidermal growth factor receptor (EGFR) expressing previously
treated metastatic colorectal cancer. It competes with endogenous ligands such as epidermal
growth factor and tumor growth factor-α and blocks stimulation of the EGFR.9 Preclinical
experiments have shown that panitumumab has both direct anti-tumor activity and can activate
a cellular immune response to SCCHN.This study provides the opportunity to better define the
population of patients that would benefit from EGFR inhibition in SCCHN.

Patients will receive single agent panitumumab in a "window of opportunity" design prior to
definitive surgical or radiation therapy. The decision to treat primarily with either
surgery or RT based therapy will be based on best medical practice by the treating physician
per NCCN guidelines at www.nccn.org.

Response to panitumumab monotherapy before surgery or radiation will be evaluated as a
continuous variable, and a median split of patients will be used to develop a signature of
drug responsiveness. An Affymetrix chip based gene signature model will then be developed by
analyzing gene expression in panitumumab sensitive versus resistant tumors. Identification
of a gene expression profile for tumor sensitivity would allow for prospective trials
treating patient populations enriched for likelihood of clinical benefit from panitumumab
therapy. It is also possible that a gene signature profile for panitumumab responsiveness
identified in SCCHN could be used as a biomarker in other epithelial cancers.

Tumor response as measured by percentage decrease in PET scan SUV level or objective
evidence of tumor response (by CT scan or direct measurement) will be the basis for
examining the activity of panitumumab by means of identifying a gene expression signature
that predicts response in this patient population. Therefore, PET scan SUV levels will be
assessed at baseline prior to any treatment. If a baseline PET/CT is obtained and a lesion
identified with SUV level ≥6, an additional pre-treatment research PET/CT will be performed
after consent (prior to dose #1 panitumumab. A second research PET/CT will also be obtained
after the first dose of panitumumab as part of this research study. If no baseline PET/CT
has been obtained, a research PET will be obtained pre-treatment, if SUV level ≥6 an
additional research PET will be obtained after the first dose of panitumumab.

All subjects will undergo imaging, biopsy and a single dose of panitumumab 9mg/kg IV. Two
to three weeks after panitumumab, imaging will be repeated and a second biopsy will be
obtained (at surgery for surgery patients) and an optional biopsy for patients receiving RT.
Subjects may receive 2 additional doses of panitumumab during their standard therapy.


Inclusion Criteria:



1. Untreated, suspected or histologically documented locally advanced clinical stage III
or IVa-b(M0)SCCHN, no evidence of distant metastases. Prior surgery with diagnosis of
SCCHN acceptable

2. Candidate for definitive surgery or radiation based therapy.

3. Fresh frozen tumor tissue must be available for genomic analysis and must pass RNA
Quality Control prior to research PET/CT #1 and/or initiating panitumumab

4. Measurable or evaluable disease

5. ECOG 0-1

6. ≥18 years of age

7. Adequate organ function

1. neutrophil count (ANC or AGC) ≥1.5 x 109/L

2. Platelet count ≥75 x 109/L

3. Hemoglobin ≥9.0 g/dL

4. Creatinine ≤1.5x ULN

5. Hepatic enzymes (AST, ALT)≤2.5x ULN, Total Bilirubin <1.5x ULN

6. Magnesium ≥ LLN

8. Negative serum pregnancy test ≤7 days before starting panitumumab (for women of
childbearing potential only)

9. Competent to comprehend, sign, and date a written informed consent form

10. Sexually active males & females of reproductive potential must agree to use adequate
method of contraception during treatment & for 6 months after study drug stopped

Exclusion Criteria:

1. History of other malignancy within past 2 years, except:

1. Malignancy treated with curative intent and with no known active disease

2. Adequately treated non-melanomatous skin cancer or lentigo maligna with no
evidence of disease

3. Adequately treated cervical carcinoma in situ with no evidence of disease

4. Prostatic intraepithelial neoplasia with no evidence of prostate cancer

2. Primary tumor of the nasopharynx (nasopharyngeal cancer), sinuses, salivary gland, or
skin. (Squamous cell carcinoma arising in/near nasopharynx is eligible)

3. Prior radiotherapy in planned field if it prevents standard radiotherapy dose and
field

4. Prior radiation for head & neck cancer

5. Prior anti-EGFR antibody therapy (e.g., cetuximab) or treatment with small molecule
EGFR inhibitors (e.g., gefitinib, erlotinib, lapatinib)

6. Prior anti-cancer treatment with: chemotherapy, hormonal therapy, immunotherapy,
experimental or approved proteins/antibodies within the past 5 years.

7. Prior systemic chemotherapy for study cancer

8. Investigational agent or therapy ≤30 days before enrollment and/or have not recovered
from such side effects

9. Continued chronic use of immunosuppressive agents during the clinical trial period
(e.g., methotrexate and cyclosporine), corticosteroids are allowed

10. Clinically significant cardiovascular disease (including MI, unstable angina,
symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤6
months before enrollment

11. History of interstitial lung disease e.g., pneumonitis or pulmonary fibrosis or
evidence of interstitial lung disease on baseline chest CT scan. Patients with CT
scan findings consistent with lung scarring from COPD or previous infection are
eligible

12. History of any medical or psychiatric condition or laboratory abnormality that in the
opinion of the investigator may increase the risk associated with the study
participation or investigational product(s) administration or may interfere with the
interpretation of the results

13. Unwilling or unable to comply with study requirements

14. Pregnant or breast feeding, or planning to become pregnant within 6 months after the
end of treatment

15. Known positive test(s) for HIV infection

16. Major surgery within 2 weeks of enrollment. Staging endoscopy with
biopsy/tonsillectomy for head & neck cancer, tracheostomy, and/or gastrostomy tube
placement eligible one day after procedure. May consent to tissue collection biopsy
pre-endoscopy/minor surgery and then begin protocol therapy one day after procedure.

17. Known allergy/hypersensitivity to any component of the study treatment(s)

18. Infection requiring intravenous antibiotics for any uncontrolled infection ≤14 days
prior to enrollment

19. Subjects on anticoagulant therapy. Aspirin and other anti-platelet agents will not be
defined as anticoagulant therapy for this study

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Identify a gene expression signature profile biomarker that predicts for sensitivity/response to panitumumab in untreated locally advanced SCCHN.

Outcome Description:

Plan will be to develop an Affymetrix chip based gene signature model by analyzing gene expression in panitumumab sensitive versus resistant tumors. Identification of a gene expression profile for tumor sensitivity would allow for prospective trials treating patient populations enriched for likelihood of clinical benefit from panitumumab therapy. It is also possible that a gene signature profile for panitumumab responsiveness identified in SCCHN could be used as a biomarker in other epithelial cancers.

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Neal Ready, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University

Authority:

United States: Food and Drug Administration

Study ID:

20080645

NCT ID:

NCT01305772

Start Date:

January 2011

Completion Date:

February 2015

Related Keywords:

  • Squamous Cell Carcinoma of the Head and Neck
  • SCCHN
  • untreated
  • Stage III or IVa-b (M0)
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Neoplasms, Squamous Cell
  • Head and Neck Neoplasms

Name

Location

Duke University Medical CenterDurham, North Carolina  27710
University of North Carolina at Chapel HillChapel Hill, North Carolina  27599