- About Pancreatic Cancer
- Get Support
Caregivers
- Get Involved
- Events
- More
2016-09-12
2017-09-21
2018-01-11
4
NCT02669914
Washington University School of Medicine
Washington University School of Medicine
INTERVENTIONAL
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.
N/A
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2016-01-22 | 2018-09-12 | 2018-10-11 |
2016-01-27 | 2018-09-12 | 2018-11-06 |
2016-02-01 | 2018-10-10 | 2018-10 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Non Randomized
Interventional Model:
Parallel
Masking:
None
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 d | DRUG: MEDI4736 |
| 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 d | DRUG: MEDI4736 |
| 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 d | DRUG: MEDI4736 |
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Overall Response Rate of Intracranial Disease | -% of subjects who achieve a complete response (CR) or partial response (CR) based on assessment of brain lesions * CR: Requires: complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; No new lesions; stable or improved nonenhancing (T2/FLAIR) lesions.; off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically. * PR: Requires:• ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. • No progression of nonmeasurable disease. • Stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at time of baseline scan. • Stable or improved clinically | Completion of treatment (estimated to be 6 months) |
| Secondary Outcome Measures | 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 | -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 | * Defined as the percentage of patients who achieve a complete response, partial response, or stable disease based on assessment of brain lesions * CR: Requires: complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; No new lesions; stable or improved nonenhancing (T2/FLAIR) lesions.; off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically. * PR: Requires:• ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. • No progression of nonmeasurable disease. • Stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at time of baseline scan. • Stable or improved clinically | Completion of treatment (estimated to be 6 months) |
| Overall Response Rate of Extracranial Disease | * Defined as the percentage of patients who achieve a complete response or partial response based on assessment of systemic lesions * Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. * Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters | Completion of treatment (estimated to be 6 months) |
| Overall Disease Control Rate of Extracranial Disease | * Defined as the percentage of patients who achieve a complete response, partial response, or stable disease based on assessment of systemic lesions * Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. * Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters * Stable disease: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study | Completion of treatment (estimated to be 6 months) |
| Overall Response Rate Considering Both Intracranial and Extracranial Disease | * Defined as the percentage of patients who achieve a complete response or partial response based on assessment of brain and systemic lesions * Intracranial disease * Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. * Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters * Extracranial disease * Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. * Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters | Completion of treatment (estimated to be 6 months) |
| Overall Disease Control Rate Considering Both Intracranial and Extracranial Disease | * Defined as the percentage of subjects who achieve a complete response, partial response, or stable disease based on assessment of brain and systemic lesions * Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline * Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) | Completion of treatment (estimated to be 6 months) |
| Duration of Response of Intracranial Disease | * Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause * Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline | Completion of treatment (estimated to be 6 months) |
| Duration of Response of Extracranial Disease | * Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause * Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) | Completion of treatment (estimated to be 6 months) |
| Duration of Response Considering Both Intracranial and Extracranial Disease | * Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause * Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline * Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) | Completion of treatment (estimated to be 6 months) |
| Progression-free Survival (PFS) | * PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. * At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Unequivocal progression of existing non-target lesions. | Up to 2 years after completion of treatment (estimated to be 2 years and 6 months) |
| Overall Survival (OS) | -Defined as the interval from the start of study therapy to death from any cause | Up to 2 years after completion of treatment (estimated to be 2 years and 6 months) |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
