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

This study is currently recruiting participants.
Verified April 2014 by University of Pittsburgh
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Robert Ferris, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00798655
First received: November 25, 2008
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.

Condition Intervention Phase
Head and Neck Cancer
Drug: Panitumumab
Drug: Cisplatin
Radiation: Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

    The primary endpoint is the probability of progression-free survival (PFS) at two years from the date of surgery. We assume that postoperative radiation and cisplatin alone would result in a PFS of 50% at 2 years {Cooper, 2004 #1641}. We are interested in assessing whether the addition of panitumumab will increase the 2 year probability of PFS to 70%. We also assume that 20-25 patients can be accrued per year. With 2 years of accrual and 1 year of additional follow up, we will require 43 evaluable patients. This will allow 90% power for a level 0.10 one sided one sample exponential test to detect an improvement from 50% to 70%.

    Secondary endpoints will be overall survival, toxicity rates and biomarker correlation with PFS. Due to the possibility that some patients may be lost to long term follow-up we plan to accrue an additional 10% of the target accrual. Therefore the sample size for this study will be 47 patients.



Estimated Enrollment: 46
Study Start Date: November 2007
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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.


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.

  Eligibility

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

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00798655

Contacts
Contact: Robert Ferris, MD 412-623-1416 ferrisrl@upmc.edu
Contact: Amy O'Sullivan, RN,BSN,MSW 412-623-4882 osullivanal@upmc.edu

Locations
United States, Pennsylvania
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Principal Investigator: Robert Ferris, MD         
Sponsors and Collaborators
Robert Ferris
Amgen
Investigators
Principal Investigator: Robert Ferris, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Robert Ferris, Division Chief, Division Head and Neck Surgery, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00798655     History of Changes
Other Study ID Numbers: 06-120
Study First Received: November 25, 2008
Last Updated: April 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
panitumumab
cisplatin

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cisplatin
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Immunologic Factors

ClinicalTrials.gov processed this record on April 17, 2014