PRISM (Panitumumab Regimen In Second-line Monotherapy of Head and Neck Cancer)

Study Overview
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Brief Summary
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To estimate the effect of second-line panitumumab monotherapy on objective response in patients with metastatic or recurrent squamous cell carcinoma of head and neck (SCCHN).

Official Title
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Phase 2, Single-Arm, Open-Label, Multi-Center Trial of Second-Line Panitumumab Monotherapy in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck

Conditions
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Cancer, Carcinoma, Head and Neck Cancer, Metastases, Metastatic Cancer, Metastatic or Recurrent Squamous Cell Carcinoma of Head and Neck, Oncology, Squamous Cell Carcinoma, Tumors

Intervention / Treatment
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* Drug: Panitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed squamous cell carcinoma of head and neck (SCCHN) of oropharynx, oral cavity, hypopharynx, or larynx with at least 1 measurable lesion using computed tomography (CT) or magnetic resonance imaging (MRI) scan Diagnosis of recurrent disease determined to be incurable by surgery or radiotherapy Karnofsky Performance Status (KPS) score ≥ 60% at screening Men or women age ≥18 years Adequate hematologic, electrolyte and hepatic functions and negative pregnancy test Exclusion Criteria: Subject received > 1 chemotherapy regimen for the treatment of metastatic or recurrent disease Concomitant chemotherapy for recurrent disease administered solely for the purpose of radiation sensitization during re-irradiation will not be counted towards this chemotherapy regimen Nasopharyngeal carcinoma, salivary gland and primary skin SCCHN, or symptomatic central nervous system (CNS) metastases History of interstitial lung disease, significant cardiovascular disease, or another primary cancer Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection Known allergy or hypersensitivity to any component of panitumumab Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, panitumumab, cetuximab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib) for recurrent or metastatic disease with the following exceptions: Prior EGFr inhibitor therapy is allowed if received as part of prior multimodality treatment (eg, as radiation sensitizer) and completed > 24 weeks prior to randomization Subjects who received no more than one dose of cetuximab and discontinued prior to progression due to documented severe infusion reaction are eligible. Significant thromboembolic event ≤ 8 weeks prior to enrollment Subjects not recovered from all previous acute radiotherapy-related toxicities History of severe skin disorder that in the opinion of the investigator may interfere with study conduct History of any medical, or psychiatric condition, or laboratory abnormality that may interfere with the interpretation of study results Subject is currently in a clinical trial ≤ 30 days prior to enrollment Subjects requiring use of immunosuppressive agents however corticosteroids are allowed Man or woman of child-bearing potential who do not consent to use adequate contraceptive precautions during the course of the study Female subject who is pregnant or breast-feeding Subject requiring major surgery using general/spinal anesthesia ≤ 28 days prior to enrollment, or minor surgery ≤ 14 days prior to enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panitumumab<br>articipants received panitumumab as an intravenous infusion at a dose of 9 mg/kg every 21 days until disease progression, unacceptable toxicity, withdrawal of consent, death, or end of study. | Drug: Panitumumab<br>* Panitumumab was administered over a 1 hour intraveneous (IV) infusion at a dose of 9 mg/kg every 21 days.<br>* Other names: Vectibix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Assessments are based on investigator's review of scans using a modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Objective response rate was defined as the percentage of participants with a best tumor response of complete response (CR) or partial response (PR) prior to initiation of subsequent anti-cancer therapy. CR or PR was confirmed no less than 28 days after the criteria for response were first met. CR: Disappearance of all target lesions, non-target lesions and no new lesions. PR: At least a 30% decrease in the size of target lesions and no progression of existing non-target lesions (defined as an increase in lesion size of ≥ 20%) and no new lesions, or, the disappearance of all target lesions and the persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease (PD) and no new lesions. | From first dose of study drug until the data cut-off date of 16 December 2010. Median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Response | Time to response was defined as the time from Study Day 1 to the first CR or PR that was subsequently confirmed. | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks) | 
| Duration of Response | Duration of response was defined as the time from first confirmed CR or PR to the earliest date of disease progression per a modified version of the RECIST criteria (version 1.0). Participants not meeting the criteria for progression by the analysis data cut-off date were censored at the date of last evaluable disease assessment. Duration of response was analyzed using the Kaplan-Meier method. PD: At least a 20% increase in the size of target lesions, or an increase of 20% or greater of non-target lesions and the lesion(s) measure ≥ 10 mm in one dimension at the time of progression, or any new lesions. | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks) | 
| Rate of Disease Control | Rate of disease control was defined as the percentage of participants with CR, PR, or stable disease (SD), as defined by a modified version of the RECIST criteria (version 1.0), prior to initiation of subsequent anti-cancer therapy. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD of target lesions and no progression of non-target lesions and no new lesions, or, if no target lesions were identified at screening, the persistence of one or more non-target lesion(s) not qualifying for either CR or PD. | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks). | 
| Time to Progression | Time to progression was defined as the time from Day 1 to the date of disease progression using a modified version of the RECIST criteria (version 1.0). Participants not meeting the criteria for progression by the analysis data cut-off date were censored at the date of last evaluable disease assessment. Time to progression was analyzed using the Kaplan-Meier method. | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks). | 
| Progression Free Survival (PFS) | PFS was defined as the time from Day 1 to the first date of disease progression, as defined by a modified version of the RECIST criteria (version 1.0), or death due to any cause (whichever comes first). Participants who were alive who did not meet the criteria for progression by the analysis data cut-off date were censored at the date of last evaluable disease assessment. PFS was analyzed using the Kaplan-Meier method. | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks). | 
| Overall Survival (OS) | Overall Survival was defined as the time from Day 1 to the date of death. For participants who did not die while on study, or were lost to follow-up, survival was censored at the end of study, or the date of last contact (whichever was first). | From first dose until the data cut-off date of 16 December 2010; median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks). | 
| Number of Participants With Adverse Events | The severity of each adverse event (AE) was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (where grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening and grade 5=fatal) with the exception of some dermatology/skin AEs that were graded using the CTCAE v3.0 with modifications. Serious AEs include any event that was fatal, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. Treatment-related adverse events (TRAEs) are those for which the investigator considered there to be a reasonable possibility that the event may have been caused by study drug. | The reporting time frame for Adverse Events is from first dose date to 30 days since the last dose date date. The median time frame is 2.4 months. |