Identification of Gene Expression Signature for Panitumumab Sensitivity in Untreated Locally Advanced SCCHN

NCT01305772 | Terminated Phase 2 Results DMC

• 2 other identifiers: Pro0002385920080645
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

SCCHN; untreated; Stage III or IVa-b (M0)

Outcome Measures

Primary Outcomes (1)

• Change in Tumor (Primary Tumor and Lymph Node) Response and Progression Between Pre- and Post- Panitumumab Therapy

  The aim of this outcome measure was to identify a gene expression signature that predicts response to panitumumab in untreated locally advanced squamous cell cancer of the head / neck (SCCHN). Response and progression were evaluated using the largest percentage change among the cases: 1) Pre-panitumumab PET scan activity, and/or; 2) Pre-panitumumab radiologic measurement compared to post-panitumumab measurement and/or; 3) Pre-panitumumab direct measurement of tumor / lymph node compared to post-panitumumab direct measurement of tumor / lymph node. Response and progression were evaluated in this single study using the criteria "changes in only the largest diameter (unidimensional measurement) of the tumor lesions were defined" in the same manner as in RECIST 1.1. No results are reported as only 2 of the 6 subjects had fresh tissue collected after the first dose of panitumumab. The study was amended to remove the biopsy procedure due to the potential risk for the participants.

  Baseline to 2 years

Secondary Outcomes (2)

• Nine (9) Month Progression Free Survival (PFS)

  9 months

• Nine (9) Month Overall Survival (OS)

  9 months

Study Arms (2)

Surgery

EXPERIMENTAL

Patients who underwent surgery after research PET/CT scans and subsequent radiation therapy with panitumumab administration

Drug: Panitumumab; Procedure: Surgery; Procedure: Radiation Therapy

Radiation Therapy

ACTIVE COMPARATOR

Patients who underwent radiation therapy only, in conjunction with panitumumab therapy.

Drug: Panitumumab; Procedure: Radiation Therapy

Interventions

Panitumumab DRUG

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.

Also known as: Vectibix®, ABX-EGF

Radiation Therapy; Surgery

Surgery PROCEDURE

Second biopsy was taken from surgical resection tissue (when possible obtained pre and post panitumumab biopsies from the same site).

Surgery

Radiation Therapy PROCEDURE

Radiation therapy was initiated within 8 weeks after surgery, or as soon as possible.

Also known as: RT

Radiation Therapy; Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Candidate for definitive surgery or radiation based therapy.
• 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
• Measurable or evaluable disease
• Eastern Cooperative Oncology Group (ECOG) 0-1
• ≥18 years of age
• Adequate organ function
• neutrophil count (ANC or AGC) ≥1.5 x 109/L
• Platelet count ≥75 x 109/L
• Hemoglobin ≥9.0 g/dL
• Creatinine ≤1.5x upper limit of normal (ULN)
• Hepatic enzymes (AST, ALT)≤2.5x ULN, Total Bilirubin \<1.5x ULN
• Magnesium ≥ Lower limit of Normal (LLN)
• Negative serum pregnancy test ≤7 days before starting panitumumab (for women of childbearing potential only)
• Competent to comprehend, sign, and date a written informed consent form

You may not qualify if:

• History of other malignancy within past 2 years, except:
• Malignancy treated with curative intent and with no known active disease
• Adequately treated non-melanomatous skin cancer or lentigo maligna with no evidence of disease
• Adequately treated cervical carcinoma in situ with no evidence of disease
• Prostatic intraepithelial neoplasia with no evidence of prostate cancer
• Primary tumor of the nasopharynx (nasopharyngeal cancer), sinuses, salivary gland, or skin. (Squamous cell carcinoma arising in/near nasopharynx is eligible)
• Prior radiotherapy in planned field if it prevents standard radiotherapy dose and field
• Prior radiation for head \& neck cancer
• Prior anti-EGFR antibody therapy (e.g., cetuximab) or treatment with small molecule EGFR inhibitors (e.g., gefitinib, erlotinib, lapatinib)
• Prior anti-cancer treatment with: chemotherapy, hormonal therapy, immunotherapy, experimental or approved proteins/antibodies within the past 5 years.
• Prior systemic chemotherapy for study cancer
• Investigational agent or therapy ≤30 days before enrollment and/or have not recovered from such side effects
• Continued chronic use of immunosuppressive agents during the clinical trial period (e.g., methotrexate and cyclosporine), corticosteroids are allowed
• Clinically significant cardiovascular disease (including myocardial infarction (MI), unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤6 months before enrollment
• 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

Sponsors & Collaborators

• Neal Ready: lead
• Amgen: collaborator

Study Sites (2)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Panitumumab; Surgical Procedures, Operative; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Neal Ready,MD
• Organization: Duke University Medical Center

neal.ready@dm.duke.edu

919-681-6932

Study Officials

• Neal Ready, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 14, 2011
• First Posted: March 1, 2011
• Study Start: January 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: May 1, 2012
• Last Updated: August 29, 2014
• Results First Posted: August 29, 2014

Record last verified: 2014-08

Locations

US (2)