- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02669914
MEDI4736 (Durvalumab) in Patients With Brain Metastasis From Epithelial-derived Tumors
A Phase II Study of MEDI4736 (Durvalumab) in Patients With Brain Metastasis From Epithelial-derived Tumors
Brain metastases are the most common intracranial malignancy occurring in 20-40% of all cancers, and the presence of CNS metastases is associated with a poor prognosis. As such, the median overall survival of patients with symptomatic brain lesions is a dismal 2-3 months regardless of tumor type. Because standard chemotherapy largely does not cross the blood brain barrier at a meaningful concentration, standard treatment is limited and usually involves surgical resection and/or stereotactic radiosurgery for isolated lesions and whole brain radiation for multiple lesions. Unfortunately, the median overall survival is only improved by about 6 months with this multimodality approach2, and there is a paucity of second-line therapies to treat recurrence. Furthermore, re-resection and re-radiation are often not feasible options due to concern for increasing complications or neurotoxicity, respectively. Thus, there is a dire clinical need for additional treatment options for this patient population.
Checkpoint blockade therapy, in particular PD-1 and PD-L1 inhibition, has recently shown clinical efficacy in multiple types of solid tumors. The investigators propose to study the efficacy of checkpoint blockade therapy in patients with solid tumors and refractory/recurrent brain metastases. The investigators will assess the efficacy of MEDI4736, a novel PD-L1 inhibitory monoclonal antibody, in this study.
Study Overview
Status
Conditions
- Kidney Cancer
- Breast Cancer
- Colorectal Cancer
- Pancreatic Cancer
- Ovarian Cancer
- Non-Small Cell Lung Cancer
- Nonsmall Cell Lung Cancer
- Cancer of the Ovary
- Renal Cancer
- Colorectal Carcinoma
- Ovary Cancer
- Cancer of Breast
- Gastroesophageal Cancer
- Cancer of the Pancreas
- Cancer of the Breast
- Cancer of Ovary
- Cancer of the Kidney
- Cancer of Kidney
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Cohort A: Histologically confirmed metastatic non-small cell lung cancer (all histologic subtypes allowed) with radiographic evidence by MRI of at least one measurable brain lesion as defined by RANO criteria that does not require corticosteroids for symptomatic control.
- Cohort B: Histologically confirmed metastatic solid tumor of epithelial origin, excluding NSCLC, including but not limited to ovarian cancer, colorectal cancer, pancreatic cancer, gastric cancer, renal cancer, bladder cancer, or breast cancer with radiographic evidence by MRI of at least one measurable brain lesion as defined by RANO criteria that does not require corticosteroids for symptomatic control.
- Cohort C: Histologically confirmed metastatic solid tumor of epithelial origin, including both NSCLC and non-NSCLC, with radiographic evidence by MRI of at least one measurable brain lesion as defined by RANO criteria that requires corticosteroids for symptomatic control.
- At least one prior treatment to a CNS-based lesion is required. Prior therapy must be completed > 2 weeks prior to enrollment. A previously treated lesion must be demonstrated by MRI to have progressed following treatment in order to be eligible. The subsequent development of a new CNS lesion that was not previously treated will be permitted and dose not require treatment followed by progression prior to enrollment. Treatment of a single CNS lesion with local therapy in the context of multifocal disease is permitted as long as at least one untreated lesions meets criteria for measurable disease. Patients should have received minimum of one line of systemic therapy.
- At least 18 years of age.
- ECOG performance status of 0 to 2
Adequate bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 8.0 g/dL
- Serum bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
- Creatinine clearance ≥ 40 mL/min/1.73 m2 by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
Negative antiviral serology:
- Negative human immunodeficiency virus (HIV) antibody.
- Negative hepatitis B surface antigen (HBsAg) and negative hepatitis B core (HBc) antibody or undetectable hepatitis B (HBV) DNA by quantitative polymerase chain reaction (PCR) testing.
- Negative hepatitis C virus (HCV) antibody or negative HCV ribonucleic acid (RNA) by quantitative PCR.
- Mean QT interval corrected for heart rate (QTc) < 470 msec calculated from 3 ECGs performed at least 2 minutes apart using Frediricia's Correction.
- Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
- Diagnosis of leptomeningeal carcinomatosis.
- Diagnosis of melanoma or other non-epithelial based malignancy such as sarcoma, neuroendocrine tumor, small cell lung cancer.
- Presence of unstable systemic disease (e.g., visceral crisis or rapid progression) in the judgment of the investigator.
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- Currently receiving any other investigational agents.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEDI4736 or other agents used in the study.
- Previous treatment with a PD-1 or PD-L1 inhibitor, including MEDI4736, or a CTLA-4 inhibitory agent.
- Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736 with the exceptions of intranasal and inhaled corticosteroids, or systemic corticosteroids in Cohort C.
- Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 21 days prior to the first dose of study drug.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension (>180/110), unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements.
- Active or prior documented autoimmune disease within the past 2 years (Note: subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded).
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
- History of prior immunodeficiency.
- History of allogeneic organ transplant.
- Known history of previous clinical diagnosis of tuberculosis.
- Receipt of live attenuated vaccination within 30 days prior to first dose of MEDI4736.
- Pregnant and/or breastfeeding or female patients of reproductive potential who are not employing an effective method of birth control.
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort A: Non-small cell lung cancer w/o corticosteroids
-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle.
Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
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Other Names:
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Experimental: Cohort B: Epithelial origin solid tumors w/o corticosteroids
-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle.
Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
|
Other Names:
|
Experimental: Cohort C: NSCLC or non-NSCLC w/corticosteroids
-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle.
Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
|
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate of Intracranial Disease
Time Frame: Completion of treatment (estimated to be 6 months)
|
-% of subjects who achieve a complete response (CR) or partial response (CR) based on assessment of brain lesions
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Completion of treatment (estimated to be 6 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events
Time Frame: 30 days after completion of treatment (estimated to be 7 months)
|
-The severity of AEs will be graded by the investigator according to the CTCAE, Version 4.03
|
30 days after completion of treatment (estimated to be 7 months)
|
Overall Disease Control Rate of Intracranial Disease
Time Frame: Completion of treatment (estimated to be 6 months)
|
|
Completion of treatment (estimated to be 6 months)
|
Overall Response Rate of Extracranial Disease
Time Frame: Completion of treatment (estimated to be 6 months)
|
|
Completion of treatment (estimated to be 6 months)
|
Overall Disease Control Rate of Extracranial Disease
Time Frame: Completion of treatment (estimated to be 6 months)
|
|
Completion of treatment (estimated to be 6 months)
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Overall Response Rate Considering Both Intracranial and Extracranial Disease
Time Frame: Completion of treatment (estimated to be 6 months)
|
|
Completion of treatment (estimated to be 6 months)
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Overall Disease Control Rate Considering Both Intracranial and Extracranial Disease
Time Frame: Completion of treatment (estimated to be 6 months)
|
|
Completion of treatment (estimated to be 6 months)
|
Duration of Response of Intracranial Disease
Time Frame: Completion of treatment (estimated to be 6 months)
|
|
Completion of treatment (estimated to be 6 months)
|
Duration of Response of Extracranial Disease
Time Frame: Completion of treatment (estimated to be 6 months)
|
|
Completion of treatment (estimated to be 6 months)
|
Duration of Response Considering Both Intracranial and Extracranial Disease
Time Frame: Completion of treatment (estimated to be 6 months)
|
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Completion of treatment (estimated to be 6 months)
|
Progression-free Survival (PFS)
Time Frame: Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)
|
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Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)
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Overall Survival (OS)
Time Frame: Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)
|
-Defined as the interval from the start of study therapy to death from any cause
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Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)
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Collaborators and Investigators
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Skin Diseases
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Endocrine Gland Neoplasms
- Breast Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Pancreatic Diseases
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Breast Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Colorectal Neoplasms
- Ovarian Neoplasms
- Brain Neoplasms
- Pancreatic Neoplasms
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Durvalumab
Other Study ID Numbers
- 201602169
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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