Identification of Gene Expression Signature for Panitumumab Sensitivity in Untreated Locally Advanced SCCHN
Condition: Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Squamous Cell Carcinoma of Head and Neck
Intervention: Panitumumab; Surgery; Radiation Therapy
Intervention description: Single dose Panitumumab 9mg/kg IV (in the vein) prior to definitive therapy (surgery or radiation therapy). Two additional doses of panitumumab 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.; Second biopsy was taken from surgical resection tissue (when possible obtained pre and post panitumumab biopsies from the same site).; Radiation therapy was initiated within 8 weeks after surgery, or as soon as possible.
Intervention MeSH terms: Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SCCHN; untreated; Stage III or IVa-b (M0)

Summary:

      The purpose of this study was 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 was added to standard adjuvant or primary radiation therapy. There were subjects
      that receive surgery followed by therapy and subjects that receive radiation therapy without
      surgery.

      Subjects entering this study had locally advanced disease that can be treated with surgery
      and/or radiation therapy. Fresh frozen tumor tissue were available for genomics analysis
      prior to initiating panitumumab therapy. If fresh frozen tissue was not available at time of
      consent, a biopsy was required to participate in this trial.
    

Eligibility 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. Eastern Cooperative Oncology Group (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 upper limit of normal (ULN)

               5. Hepatic enzymes (AST, ALT)≤2.5x ULN, Total Bilirubin <1.5x ULN

               6. Magnesium ≥ Lower limit of Normal (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 myocardial infarction (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 chronic obstructive pulmonary disease
             (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