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

• Sponsor: Robert Ferris (Other)
• Overall Status: Completed
• CT.gov ID: NCT00798655
• Collaborator: Amgen (Industry)
• Enrollment: 46
• Location: 1
• Arm: 1
• Actual Duration (Months): 108.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Panitumumab; Drug: Cisplatin; Radiation: Radiation Therapy	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer
• Actual Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Nov 9, 2016

Arms and Interventions

Arm

Intervention/Treatment

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.

Outcome Measures

Primary Outcome Measures

1. Probability of Progression-free Survival (PFS) at 2 Years [Up to 90 months for cohort; individual patients up to 24 months after study treatment]

Secondary Outcome Measures

1. Probability of 2-year Overall Survival [Up to 90 months for cohort; individual patients up to 24 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• Robert Ferris
• Amgen

Investigators

• Principal Investigator: Robert Ferris, MD, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Ferris, Division Chief, Division Head and Neck Surgery, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00798655
• Other Study ID Numbers: 06-120
• First Posted: Nov 26, 2008
• Last Update Posted: Oct 3, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by Robert Ferris, Division Chief, Division Head and Neck Surgery, University of Pittsburgh: panitumumab; cisplatin; radiation
• Additional relevant MeSH terms: Neoplasms; Head and Neck Neoplasms; Cisplatin; Panitumumab

Study Results

Participant Flow

Pre-assignment Detail	Study included patients with pathologic stage III or IVA squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or human-papillomavirus (HPV) -negative oropharynx, without gross residual tumor, featuring high-risk factors (margins <1mm, extracapsular extension, perineural or angiolymphatic invasion, or ≥2 positive lymph nodes).

Arm/Group Title	Radiation Therapy+Cisplatin+Panitumumab
Arm/Group Description	Postoperative treatment consisted of standard radiation therapy (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m^2 and weekly panitumumab 2.5 mg/kg. (no prior chemotherapy, biologic/targeted therapy, or radiation therapy).
Period Title: Overall Study
STARTED	46
COMPLETED	44
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Radiation Therapy+Cisplatin+Panitumumab
Arm/Group Description	Postoperative treatment consisted of standard radiation therapy (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m^2 and weekly panitumumab 2.5 mg/kg. (no prior chemotherapy, biologic/targeted therapy, or radiation therapy).
Overall Participants	44
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	8 18.2%
Male	36 81.8%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Patients who received 60-66 Gy over 6-7 weeks) concurrent with cisplatin 30 mg/m^2 and at least once dose of panitumumab 2.5 mg/kg.

Arm/Group Title	Radiation Therapy+Cisplatin+Panitumumab
Arm/Group Description	Postoperative treatment consisted of standard radiation therapy (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m^2 and weekly panitumumab 2.5 mg/kg. (no prior chemotherapy, biologic/targeted therapy, or radiation therapy).
Measure Participants	44
Number (95% Confidence Interval) [percentage of participants]	70 159.1%

2. Secondary Outcome

Title	Probability of 2-year Overall Survival
Time Frame	Up to 90 months for cohort; individual patients up to 24 months

Outcome Measure Data

Analysis Population Description

Patients who received 60-66 Gy over 6-7 weeks) concurrent with cisplatin 30 mg/m^2 and at least once dose of panitumumab 2.5 mg/kg.

Arm/Group Title	Radiation Therapy+Cisplatin+Panitumumab
Arm/Group Description	Postoperative treatment consisted of standard radiation therapy (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m^2 and weekly panitumumab 2.5 mg/kg. (no prior chemotherapy, biologic/targeted therapy, or radiation therapy).
Measure Participants	44
Number (95% Confidence Interval) [percentage of participants]	72 163.6%

Adverse Events

Arm/Group Title	Radiation Therapy+Cisplatin+Panitumumab
Arm/Group Description	Postoperative treatment consisted of standard radiation therapy (60-66 Gy over 6-7 weeks) concurrent with weekly cisplatin 30 mg/m^2 and weekly panitumumab 2.5 mg/kg. (no prior chemotherapy, biologic/targeted therapy, or radiation therapy).
All Cause Mortality
	Radiation Therapy+Cisplatin+Panitumumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Radiation Therapy+Cisplatin+Panitumumab
	Affected / at Risk (%)	# Events
Total	18/46 (39.1%)
Blood and lymphatic system disorders
Hemoglobin	1/46 (2.2%)
Lymphopenia	3/46 (6.5%)
Cardiac disorders
Hypotension	1/46 (2.2%)
Gastrointestinal disorders
Anorexia	1/46 (2.2%)
Dehydration	1/46 (2.2%)
Diarrhea	1/46 (2.2%)
Dry mouth/salivary gland (xerostomia)	1/46 (2.2%)
Dysphagia (difficulty swallowing)	1/46 (2.2%)
Mucositis/stomatitis (clinical exam), Oral cavity	2/46 (4.3%)
Nausea	1/46 (2.2%)
Vomiting	1/46 (2.2%)
General disorders
Pain, Chest/thorax NOS	1/46 (2.2%)
Pain, Pain NOS	1/46 (2.2%)
Weight loss	1/46 (2.2%)
Immune system disorders
Allergic reaction/hypersensitivity	1/46 (2.2%)
Infections and infestations
Febrile neutropenia	1/46 (2.2%)
Infection - Other (Specify, __)	1/46 (2.2%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Trachea	1/46 (2.2%)
Nervous system disorders
Dizziness	1/46 (2.2%)
Psychosis (hallucinations/delusions)	1/46 (2.2%)
Other (Not Including Serious) Adverse Events
	Radiation Therapy+Cisplatin+Panitumumab
	Affected / at Risk (%)	# Events
Total	46/46 (100%)
Blood and lymphatic system disorders
Platelets	3/46 (6.5%)
Neutrophils/granulocytes (ANC/AGC)	3/46 (6.5%)
Lymphopenia	3/46 (6.5%)
Hemoglobin	3/46 (6.5%)
Leukocytes (total WBC)	3/46 (6.5%)
Lymphatics - Other (Specify, __)	9/46 (19.6%)
Edema: head and neck	10/46 (21.7%)
Cardiac disorders
Hypotension	3/46 (6.5%)
Hypertension	3/46 (6.5%)
Ear and labyrinth disorders
Auditory/Ear - Other (Specify, __)	3/46 (6.5%)
Tinnitus	3/46 (6.5%)
Endocrine disorders
Thyroid function, low (hypothyroidism)	6/46 (13%)
Gastrointestinal disorders
Gastrointestinal - Other (Specify, __)	6/46 (13%)
Dehydration	6/46 (13%)
Diarrhea	6/46 (13%)
Heartburn/dyspepsia	7/46 (15.2%)
Salivary gland changes/saliva	7/46 (15.2%)
Anorexia	7/46 (15.2%)
Taste alteration (dysgeusia)	7/46 (15.2%)
Vomiting	7/46 (15.2%)
Dry mouth/salivary gland (xerostomia)	7/46 (15.2%)
Mucositis/stomatitis (functional/symptomatic), Oral cavity	8/46 (17.4%)
Constipation	8/46 (17.4%)
Nausea	8/46 (17.4%)
Dysphagia (difficulty swallowing)	8/46 (17.4%)
Mucositis/stomatitis (clinical exam), Oral cavity	8/46 (17.4%)
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	3/46 (6.5%)
Rigors/chills	3/46 (6.5%)
Insomnia	4/46 (8.7%)
Fatigue (asthenia, lethargy, malaise)	4/46 (8.7%)
Weight loss	4/46 (8.7%)
Pain, Esophagus	27/46 (58.7%)
Pain, Pain NOS	27/46 (58.7%)
Pain, Neck	29/46 (63%)
Pain, Throat/pharynx/larynx	29/46 (63%)
Pain, Oral cavity	30/46 (65.2%)
Pain - Other (Specify, __)	30/46 (65.2%)
Infections and infestations
Infection - Other (Specify, __)	9/46 (19.6%)
Metabolism and nutrition disorders
Creatinine	10/46 (21.7%)
Calcium, serum-high (hypercalcemia)	10/46 (21.7%)
Glucose, serum-low (hypoglycemia)	10/46 (21.7%)
Phosphate, serum-low (hypophosphatemia)	11/46 (23.9%)
Bilirubin (hyperbilirubinemia)	11/46 (23.9%)
Alkaline phosphatase	11/46 (23.9%)
Magnesium, serum-high (hypermagnesemia)	12/46 (26.1%)
Metabolic/Laboratory - Other (Specify, __)	13/46 (28.3%)
ALT, SGPT (serum glutamic pyruvic transaminase)	14/46 (30.4%)
Potassium, serum-high (hyperkalemia)	14/46 (30.4%)
AST, SGOT(serum glutamic oxaloacetic transaminase)	15/46 (32.6%)
Potassium, serum-low (hypokalemia)	15/46 (32.6%)
Calcium, serum-low (hypocalcemia)	15/46 (32.6%)
Magnesium, serum-low (hypomagnesemia)	15/46 (32.6%)
Albumin, serum-low (hypoalbuminemia)	16/46 (34.8%)
Glucose, serum-high (hyperglycemia)	18/46 (39.1%)
Sodium, serum-low (hyponatremia)	19/46 (41.3%)
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other (Specify, __)	22/46 (47.8%)
Nervous system disorders
Mood alteration, Depression	22/46 (47.8%)
Dizziness	23/46 (50%)
Neurology - Other (Specify, __)	24/46 (52.2%)
Mood alteration, Anxiety	24/46 (52.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other (Specify, __)	31/46 (67.4%)
Dyspnea (shortness of breath)	31/46 (67.4%)
Cough	35/46 (76.1%)
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	35/46 (76.1%)
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)	4/46 (8.7%)
Hyperpigmentation	4/46 (8.7%)
Ulceration	4/46 (8.7%)
Wound complication, non-infectious	4/46 (8.7%)
Rash/desquamation	4/46 (8.7%)
Pruritus/itching	4/46 (8.7%)
Dermatology/Skin - Other (Specify, __)	5/46 (10.9%)
Dry skin	5/46 (10.9%)
Rash: dermatitis associated with radiation, Chemoradiation	5/46 (10.9%)
Rash: dermatitis associated with radiation, Radiation	5/46 (10.9%)
Rash: acne/acneiform	5/46 (10.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.