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Identification of Gene Expression Signature for Panitumumab Sensitivity in Untreated Locally Advanced SCCHN (TOP 0901)

This study is currently recruiting participants.
Verified February 2011 by Duke University
Sponsor:
Collaborator:
Amgen
Information provided by:
Duke University
ClinicalTrials.gov Identifier:
NCT01305772
First received: February 14, 2011
Last updated: February 25, 2011
Last verified: February 2011
History of Changes
  Purpose

The purpose of this study is to identify which cancer-related genes are turned on or turned off in order to determine how well a patient will respond to the study drug, panitumumab. Panitumumab will be added to standard adjuvant or primary radiation therapy. There will be those subjects that receive surgery followed by therapy and subjects that receive radiation therapy without surgery.

Subjects entering this study must have locally advanced disease that can be treated with surgery and/or radiation therapy. Fresh frozen tumor tissue must be available for genomics analysis prior to initiating panitumumab therapy. If fresh frozen tissue is not available at time of consent, a biopsy will be required to participate in this trial.


Condition Intervention Phase
Squamous Cell Carcinoma of the Head and Neck
 Drug: Panitumumab
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Identification of a Gene Expression Signature Profile for Panitumumab Sensitivity in Untreated Locally Advanced Squamous Cell Cancer of the Head and Neck (SCCHN)

Resource links provided by NLM:

Drug Information available for: Panitumumab
U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:
  • Identify a gene expression signature profile biomarker that predicts for sensitivity/response to panitumumab in untreated locally advanced SCCHN. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 1. Compare a metagene-based gene expression signature for EGFR pathway activation to other previously identified markers/models representative of EGFR pathway activation. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The association between response to panitumumab treatment and the metagene-based gene expression signature for EGFR pathway activation will be assessed using Spearman rank correlation coefficient. If a significant association is observed, the predictive value of the EGFR signature will be ascertained in an exploratory manner using receiver operator characteristic (ROC) curves.

  • Compare gene expression for EGFR pathway before and after treatment with panitumumab. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Changes in EGFR pathway activation will be evaluated using descriptive statistics and a significant trend will be evaluated with the non-parametric Wilcoxon signed rank test.

  • Compare the response rates, progression-free survival and overall survival rates of loco-regional disease control maintained for 2 years to historical controls selected from two previously conducted(ongoing)trials with locally advanced SCCHN. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Response/progression evaluated using % change in:1)pre-panitumumab PET scan activity compared to post-panitumumab activity,and2)pre-panitumumab radiologic measurement compared to post-panitumumab measurement and/or3)pre-panitumumab direct measurement of tumor/lymph node compared to post-panitumumab direct measurement of tumor/lymph node. This study will use "changes in only the largest diameter (unidimensional measurement) of the tumor lesions will be defined" in the same manner as in RECIST 1.1.Radiologic response or objective response by direct measurement will be defined using RECIST 1.1.

  • Exploratory DNA and biomarker analysis of pretreatment blood sample. [ Time Frame: 2 year ] [ Designated as safety issue: No ]
    This work will be exploratory and hypothesis generating in examining alterations both genome-wide and in specific targets such as epidermal growth factor receptor (EGFR).

  • Profile tumor tissue DNA for any genetic alterations as compared to normal tissue. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Tumor tissue DNA will be used for investigation of genetic alterations as compared to normal tissue. This work will be exploratory and hypothesis generating in examining alterations both genome-wide and in specific targets


Estimated Enrollment: 33
Study Start Date: January 2011
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panitumumab Drug: Panitumumab
Single dose Panitumumab 9mg/kg IV (in the vein) prior to definitive therapy (surgery or radiation therapy). Two additional doses of pantitumumab 9mg/kg IV may be given at weeks 1 & 4 of RT alone or weeks 1 & 4 of cisplatin/RT if they tolerated first dose of panitumumab.
Other Names:
  • Vectibix®
  • ABX-EGF

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01305772

Contacts
Contact: Deb Shoemaker, RN 919-668-6498 shoem002@mc.duke.edu
Contact: Traci Foster, RN 919-681-8659 traci.foster@duke.edu

Locations
United States, North Carolina
University of North Carolina at Chapel Hill Not yet recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: D. N. Hayes, MD, MPH         hayes@med.unc.edu    
Sub-Investigator: Marion Couch, MD            
Sub-Investigator: Bhisham Chera, MD            
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Neal Ready, MD, PhD     919-681-6932     neal.ready@duke.edu    
Sub-Investigator: David Brizel, MD            
Sub-Investigator: Richard Scher, MD            
Sub-Investigator: Jenny Hoang, MD            
Sub-Investigator: Frank Dunphy, MD            
Sub-Investigator: Michael Datto, MD, PhD            
Sub-Investigator: David Yoo, MD            
Sub-Investigator: Walter Lee, MD            
Sponsors and Collaborators
Duke University
Amgen
Investigators
Principal Investigator: Neal Ready, MD, PhD Duke University
  More Information

No publications provided

Responsible Party: Neal Ready, MD, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01305772     History of Changes
Other Study ID Numbers: 20080645
Study First Received: February 14, 2011
Last Updated: February 25, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
SCCHN
untreated
Stage III or IVa-b (M0)

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
 Neoplasms
Neoplasms by Site
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013