Brief Summary
Primary Objective: To assess the efficacy of MEDI4736 monotherapy in terms of ORR
Brief Title
Phase II Study of MEDI4736 Monotherapy in Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Detailed Description
This is a phase II, multi-center, single-arm, global study of MEDI4736 monotherapy in patients with PD-L1 positive recurrent or metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN), who have progressed during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Recurrent or Metastatic PD-L1-positive Squamous Cell Carcinoma of the Head and Neck
Eligibility Criteria
Inclusion Criteria:
* Age ≥18 years
* Written informed consent obtained from the patient/legal representative
* Histologically confirmed recurrent or metastatic SCCHN
* Tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent.
* Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
* Confirmed PD-L1-positive SCCHN by Ventana SP263 assay
* WHO/ECOG performance status of 0 or 1
* At least 1 measurable lesion at baseline
* No prior exposure to immune-mediated therapy
* Adequate organ and marrow function
* Evidence of post-menopausal status or negative urinary or serum pregnancy test.
Exclusion Criteria:
* Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck
* Received more than 1 systematic palliative regimen for recurrent or metastatic disease
* Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment
* Prior randomization or treatment in a previous MEDI4736 and/or tremelimumab clinical study regardless of treatment arm assignment or receipt of any investigational anticancer therapy within 28 days or 5 half-lives
* Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment
* Major surgical procedure within 28 days prior to the first dose of Investigational Product
* Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion
* Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736
* History of allogeneic organ transplantation
* Active or prior documented autoimmune or inflammatory disorders;
* Uncontrolled intercurrent illness
* Another primary malignancy
* Patients with history of brain metastases, spinal cord compression, or leptomeningeal carcinomatosis
* History of active primary immunodeficiency
* Known history of previous tuberculosis
* Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
* Receipt of live, attenuated vaccine within 30 days prior to the first dose of MEDI4736
* Pregnant or breast-feeding female patients
* Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction
* Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results
* Age ≥18 years
* Written informed consent obtained from the patient/legal representative
* Histologically confirmed recurrent or metastatic SCCHN
* Tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent.
* Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
* Confirmed PD-L1-positive SCCHN by Ventana SP263 assay
* WHO/ECOG performance status of 0 or 1
* At least 1 measurable lesion at baseline
* No prior exposure to immune-mediated therapy
* Adequate organ and marrow function
* Evidence of post-menopausal status or negative urinary or serum pregnancy test.
Exclusion Criteria:
* Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck
* Received more than 1 systematic palliative regimen for recurrent or metastatic disease
* Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment
* Prior randomization or treatment in a previous MEDI4736 and/or tremelimumab clinical study regardless of treatment arm assignment or receipt of any investigational anticancer therapy within 28 days or 5 half-lives
* Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment
* Major surgical procedure within 28 days prior to the first dose of Investigational Product
* Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion
* Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736
* History of allogeneic organ transplantation
* Active or prior documented autoimmune or inflammatory disorders;
* Uncontrolled intercurrent illness
* Another primary malignancy
* Patients with history of brain metastases, spinal cord compression, or leptomeningeal carcinomatosis
* History of active primary immunodeficiency
* Known history of previous tuberculosis
* Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
* Receipt of live, attenuated vaccine within 30 days prior to the first dose of MEDI4736
* Pregnant or breast-feeding female patients
* Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction
* Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results
Inclusion Criteria
Inclusion Criteria:
* Age ≥18 years
* Written informed consent obtained from the patient/legal representative
* Histologically confirmed recurrent or metastatic SCCHN
* Tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent.
* Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
* Confirmed PD-L1-positive SCCHN by Ventana SP263 assay
* WHO/ECOG performance status of 0 or 1
* At least 1 measurable lesion at baseline
* No prior exposure to immune-mediated therapy
* Adequate organ and marrow function
* Evidence of post-menopausal status or negative urinary or serum pregnancy test.
* Age ≥18 years
* Written informed consent obtained from the patient/legal representative
* Histologically confirmed recurrent or metastatic SCCHN
* Tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent.
* Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
* Confirmed PD-L1-positive SCCHN by Ventana SP263 assay
* WHO/ECOG performance status of 0 or 1
* At least 1 measurable lesion at baseline
* No prior exposure to immune-mediated therapy
* Adequate organ and marrow function
* Evidence of post-menopausal status or negative urinary or serum pregnancy test.
Gender
All
Gender Based
false
Keywords
Head and neck cancer; SCCHN
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
130 Years
Minimum Age
18 Years
NCT Id
NCT02207530
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D4193C00001
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase II, Multi-Center, Single-Arm, Global Study of MEDI4736 Monotherapy in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Primary Outcomes
Outcome Description
Objective response rate (per RECIST 1.1 as assessed by blinded independent central review \[BICR\]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR.
Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1. criteria are: Complete response \[CR\] = disappearance of all target lesions since baseline; and partial response \[PR\] = at least a 30% decrease in the sum of the diameters of target lesions.
Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1. criteria are: Complete response \[CR\] = disappearance of all target lesions since baseline; and partial response \[PR\] = at least a 30% decrease in the sum of the diameters of target lesions.
Outcome Measure
Objective Response Rate (ORR)
Outcome Time Frame
12 months
Secondary Outcomes
Outcome Description
Best objective response based on BICR assessments according to RECIST v1.1. Response required confirmation after 4 weeks.
Unconfirmed complete (CR) or partial response (PR) refers to CR or PR achieved but either no confirmation assessment was performed or a confirmation assessment was performed but response was not confirmed.
Unconfirmed complete (CR) or partial response (PR) refers to CR or PR achieved but either no confirmation assessment was performed or a confirmation assessment was performed but response was not confirmed.
Outcome Time Frame
12 months
Outcome Measure
Best Objective Response
Outcome Description
Participants remaining in response - based on BICR assessments according to RECIST v1.1.
An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Outcome Time Frame
12 months
Outcome Measure
Duration of Response- Participants Remaining in Response
Outcome Description
Duration of objective response in patients with objective response based on BICR assessments according to RECIST v1.1.
Duration of response was the time from the first documentation of complete or partial response until the date of progression (which was subsequently confirmed), death, or the last evaluable RECIST assessment for patients that did not progress.
An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Duration of response was the time from the first documentation of complete or partial response until the date of progression (which was subsequently confirmed), death, or the last evaluable RECIST assessment for patients that did not progress.
An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Outcome Time Frame
12 months
Outcome Measure
Duration of Response
Outcome Description
Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1
Outcome Time Frame
12 months
Outcome Measure
Time to Onset of Response From First Dose
Outcome Description
Disease control (DCR) at 6 months based on BICR assessments according to RECIST v1.1.
DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD):
* Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following the start of study treatment.
* Method 2: Patients who had a best objective response of CR or PR within 24 weeks or had demonstrated SD for a minimum interval of 16 weeks following the start of study treatment.
DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD):
* Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following the start of study treatment.
* Method 2: Patients who had a best objective response of CR or PR within 24 weeks or had demonstrated SD for a minimum interval of 16 weeks following the start of study treatment.
Outcome Time Frame
6 months
Outcome Measure
Disease Control at 6 Months
Outcome Description
Progression status based on BICR assessments according to RECIST v1.1 at time of PFS analysis.
Progression was defined as the time from the date of first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression.
Progression was defined as the time from the date of first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression.
Outcome Time Frame
12 months
Outcome Measure
Progression-free Survival
Outcome Description
Survival status at time of overall survival analysis. 'Still in survival follow-up' includes patients known to be alive at data cut-off. 'Terminated prior to death' includes patients with unknown survival status, or who were lost to follow-up.
Outcome Time Frame
12 months
Outcome Measure
Overall Survival (OS)
Outcome Description
Improvement in quality of life was assessed using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires:
* The impact of treatment on Health-Related Quality of Life, functioning, and symptoms was evaluated using the EORTC QLQ-C30 v3.
* Head and neck cancer-specific symptoms were evaluated using the EORTC QLQ-H\&N35.
Function or global health status/quality of life improvement was defined as patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (an increase from baseline score ≥10). Symptom improvement was defined as 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10).
Scale improvement was defined as patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10).
* The impact of treatment on Health-Related Quality of Life, functioning, and symptoms was evaluated using the EORTC QLQ-C30 v3.
* Head and neck cancer-specific symptoms were evaluated using the EORTC QLQ-H\&N35.
Function or global health status/quality of life improvement was defined as patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (an increase from baseline score ≥10). Symptom improvement was defined as 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10).
Scale improvement was defined as patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10).
Outcome Time Frame
12 months
Outcome Measure
Quality of Life
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
130
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Missak Haigentz
Investigator Email
mhaigent@montefiore.org
Investigator Phone
718-920-4826