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Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer

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ClinicalTrials.gov Identifier: NCT00798655
Recruitment Status : Completed
First Posted : November 26, 2008
Results First Posted : August 9, 2016
Last Update Posted : October 3, 2017
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Robert Ferris, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE November 25, 2008
First Posted Date  ICMJE November 26, 2008
Results First Submitted Date  ICMJE June 28, 2016
Results First Posted Date  ICMJE August 9, 2016
Last Update Posted Date October 3, 2017
Actual Study Start Date  ICMJE November 2007
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2016)
Probability of Progression-free Survival (PFS) at 2 Years [ Time Frame: Up to 90 months for cohort; individual patients up to 24 months after study treatment ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 25, 2008)
To determine the progression-free survival (primary endpoint) and overall survival, and treatment toxicities. Also, we plan to study EGFR-related and immune biomarkers in baseline tumor tissue as well as blood samples obtained prior and after therapy. [ Time Frame: 8 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2016)
Probability of 2-year Overall Survival [ Time Frame: Up to 90 months for cohort; individual patients up to 24 months ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer
Official Title  ICMJE A Phase II Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer
Brief Summary

The objectives for this study is as follows:

  • Primary:

    • To evaluate the progression-free survival of locoregionally advanced (stages III/IV) SCCHN patients undergoing postoperative chemoradiotherapy with panitumumab.
  • Secondary:

    • To evaluate the overall survival, event-free survival, and toxicities.
    • To correlate efficacy parameters with 1) EGFR and downstream pathway activation, 2) FcyR polymorphisms, and 3) serum cytokine profiles. More specifically, the aim is to demonstrate the usefulness of biomarkers (downstream signaling molecules, FcyR polymorphisms, or tumor and serum cytokine(s) in predicting progression-free survival in patients with SCCHN treated with the above treatment. Specific biomarkers that relate to Epidermal Growth Factor Receptor and angiogenesis, including EGFR, pEGFR, Src, pMAPK, pSTAT3, pSTAT5, pSTAT1, pAKT, p38, p21, p27, PARP, E-cadherin, p-ErbB3, Ki67, VEGF, and IL-8, using reverse phase protein microarrays (RPPA) will be tested in baseline archival paraffin-embedded tumor tissue. To collect tumor tissue from pretreatment biopsies for cytokine/chemokine and immune biomarker studies on tumor tissue. We plan to investigate the expression of pAKT, pMAPK, and other EGFR pathway-related markers as well angiogenesis biomarkers. In addition, EGFR polymorphisms will be studied in tumor tissue samples and serum. Additional studies may be performed in the future. Some of these studies may be performed by Amgen.
Detailed Description Pathologically staged squamous cell carcinoma of the head and neck, stage III or IVa (AJCC 6th edition 2002) of the oral cavity, larynx, or hypopharynx that is status post potentially curative surgical resection without gross residual tumor, except the following: a)T3N0 laryngeal primary and b) any T1N1, if there are no high-risk pathologic features (high risk defined as positive margins, extracapsular spread, and perineural or angiolymphatic invasion). Patients should not have gross residual disease. No prior chemotherapy, biologic/targeted therapy (including any prior therapy which specifically and directly targets the EGFR pathway), or radiotherapy for head and neck cancer. A brief course, up to 2 weeks, of prior neoadjuvant single-agent biologic/targeted therapy of any type (except EGFR monoclonal antibodies) prior to surgical resection is permitted. No more than 7 weeks (minimum of 3 weeks) should have elapsed between surgery and initiation of radiation. No prior radiation or chemotherapy for head and neck cancer. ECOG performance status of 0-1. Patients must have normal organ and marrow function as defined below: absolute neutrophil count >=1,500/mL; Platelets >=100,000/mL; Hemoglobin >=10 g/dL; Total bilirubin 1.5 x normal institutional limits; Creatinine clearance > 60 ml/min. No prior invasive malignancy unless the DFS is 3 years or more. Age >= 18 years. Pregnant or breast-feeding women are excluded (see exclusion criteria). Informed consent must be obtained from all patients prior to beginning therapy. Patients should have the ability to understand and the willingness to sign a written informed consent document. Patients who have tumor tissue available from previous diagnostic or therapeutic procedures should submit the specimen for assessment of EGFR and related biomarkers after signing informed consent. In-Eligibility: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction. All patients will have a baseline EKG. If abnormalities consistent with active coronary artery disease are detected, the patient will be referred to a cardiologist for appropriate evaluation and management prior to treatment on study. Patients with history of hypertension must be well-controlled upon study entry (≤150/90) on a stable regimen of anti-hypertensive therapy. Patients should not have any prior history of hypertensive crisis or hypertensive encephalopathy.Patients may not be receiving any other investigational agents. No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, or malignancy that has been treated with a curative intent with a 3-year disease-free survival. No patients with significant baseline sensory or motor neurologic deficits (> grade I neuropathy) will be treated on this study. Pregnant women are excluded from this study because chemotherapy and radiation therapy have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued if the mother is treated with chemotherapy. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. All WOCBP MUST have a negative urine pregnancy test at baseline, or within 7 days prior to receiving investigational product. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG. If the urine pregnancy test is positive, a serum pregnancy test will then be performed to confirm the result. In the event that both the urine and serum pregnancy tests are positive, the subject must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. The Investigator must immediately notify Amgen in the event of a confirmed pregnancy in a patient participating in the study. Prior severe infusion reaction to a human monoclonal antibody.Prior severe infusion reaction to a human monoclonal antibody.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cancer of Head
  • Cancer of Head and Neck
  • Cancer of Neck
  • Cancer of the Head
  • Cancer of the Head and Neck
  • Cancer of the Neck
  • Head and Neck Cancer
  • Head Cancer
  • Head Neoplasms
  • Head, Neck Neoplasms
  • Neck Cancer
  • Neck Neoplasms
  • Neoplasms, Head
  • Neoplasms, Head and Neck
  • Neoplasms, Neck
  • Neoplasms, Upper Aerodigestive Tract
  • UADT Neoplasms
  • Upper Aerodigestive Tract Neoplasms
Intervention  ICMJE
  • Drug: Panitumumab

    Panitumumab, starting dose, 2.5mg/kg will be given as an intravenous infusion (IV) through a vein in your arm, once a week before radiation and chemotherapy for 6 weeks; treatment takes about an hour.

    The panitumumab dose will be calculated based on the subject's actual weekly body weight

    Other Names:
    • ABX-EGF
    • Vectibix
  • Drug: Cisplatin
    Cisplatin, 30 mg/m2 will be given as an intravenous infusion (IV) through a vein in your arm, once a week before radiation therapy and after panitumumab for 6 weeks; treatment takes about an hour
    Other Names:
    • cisplatinum
    • cis-diamminedichloroplatinum(II)
    • Platin
  • Radiation: Radiation Therapy

    Radiation Therapy 60-66 Gy/200 cGy/daily, five days a week, Monday through Friday, except on weekends and holidays, for six weeks; treatments take about 20 minutes.

    Radiation will be administered either prior to chemo treatment or after chemo treatment as long as radiation is given on the same day.

Study Arms  ICMJE Experimental: Panitumumab, Cisplatin plus radiation
Standard radiation 60-66 Gy with 200 cGy daily fractions in 6-7 weeks Cisplatin* 30 mg/m2 IV, weekly during radiation (total of 6-7 doses based upon radiation therapy dose requirements) Panitumumab 2.5 mg/Kg IV, weekly during radiation (total of 6-7 doses based upon radiation therapy dose requirements)
Interventions:
  • Drug: Panitumumab
  • Drug: Cisplatin
  • Radiation: Radiation Therapy
Publications * Ferris RL, Geiger JL, Trivedi S, Schmitt NC, Heron DE, Johnson JT, Kim S, Duvvuri U, Clump DA, Bauman JE, Ohr JP, Gooding WE, Argiris A. Phase II trial of post-operative radiotherapy with concurrent cisplatin plus panitumumab in patients with high-risk, resected head and neck cancer. Ann Oncol. 2016 Dec;27(12):2257-2262. doi: 10.1093/annonc/mdw428. Epub 2016 Oct 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 14, 2014)
46
Original Estimated Enrollment  ICMJE
 (submitted: November 25, 2008)
43
Actual Study Completion Date  ICMJE November 9, 2016
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pathologically staged squamous cell carcinoma of the head and neck, stage III or IVa (AJCC 6th edition 2002) of the oral cavity, larynx, or hypopharynx that is status post potentially curative surgical resection without gross residual tumor, except the following: a)T3N0 laryngeal primary and b) any T1N1, if there are no high-risk pathologic features (high risk defined as positive margins, extracapsular spread, and perineural or angiolymphatic invasion).
  • Patients should not have gross residual disease.
  • No prior chemotherapy, biologic/targeted therapy (including any prior therapy which specifically and directly targets the EGFR pathway), or radiotherapy for head and neck cancer. A brief course, up to 2 weeks, of prior neoadjuvant single-agent biologic/targeted therapy of any type (except EGFR monoclonal antibodies) prior to surgical resection is permitted.
  • No more than 6 7 weeks (minimum of 3 weeks) should have elapsed between surgery and initiation of radiation.
  • No prior radiation or chemotherapy for head and neck cancer.
  • ECOG performance status of 0-1
  • Patients must have normal organ and marrow function Absolute neutrophil count >/=1,500/uL Platelets >/=100,000/uL Hemoglobin >/= 10 g/dL Total bilirubin <1.5 x normal institutional limits Creatinine clearance > 60 mL/min
  • No prior invasive malignancy unless the DFS is 3 years or more.
  • Age > 18 years.
  • Pregnant or breast-feeding women are excluded (see exclusion criteria).
  • Informed consent must be obtained from all patients prior to beginning therapy. Patients should have the ability to understand and the willingness to sign a written informed consent document.
  • Patients who have tumor tissue available from previous diagnostic or therapeutic procedures should submit the specimen for assessment of EGFR and related biomarkers after signing informed consent.

Exclusion Criteria:

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction. All patients will have a baseline EKG. If abnormalities consistent with active coronary artery disease are detected, the patient will be referred to a cardiologist for appropriate evaluation and management prior to treatment on study.. Patients with history of hypertension must be well-controlled upon study entry (≤150/90) on a stable regimen of anti-hypertensive therapy. Patients should not have any prior history of hypertensive crisis or hypertensive encephalopathy.
  • Patients may not be receiving any other investigational agents.
  • No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, or malignancy that has been treated with a curative intent with a 3-year disease-free survival.
  • No patients with significant baseline sensory or motor neurologic deficits(> grade I neuropathy) will be treated on this study.
  • Pregnant women are excluded from this study because chemotherapy and radiation therapy have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued if the mother is treated with chemotherapy.
  • Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
  • All WOCBP MUST have a negative urine pregnancy test at baseline, or within 7 days prior to receiving investigational product. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG. If the urine pregnancy test is positive, a serum pregnancy test will then be performed to confirm the result. In the event that both the urine and serum pregnancy tests are positive, the subject must not receive investigational product and must not be enrolled in the study.
  • In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation.

The Investigator must immediately notify Amgen in the event of a confirmed pregnancy in a patient participating in the study.

-Prior severe infusion reaction to a human monoclonal antibody.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00798655
Other Study ID Numbers  ICMJE 06-120
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Robert Ferris, University of Pittsburgh
Study Sponsor  ICMJE Robert Ferris
Collaborators  ICMJE Amgen
Investigators  ICMJE
Principal Investigator: Robert Ferris, MD University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP