MEDI4736 (Durvalumab) in Patients With Brain Metastasis From Epithelial-derived Tumors

NCT02669914 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 201602169
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nonsmall Cell Lung Cancer; Breast Cancer; Cancer of Breast; Cancer of the Breast; Gastroesophageal Cancer; Pancreatic Cancer; Cancer of the Pancreas; Colorectal Cancer; Colorectal Carcinoma; Renal Cancer; Kidney Cancer; Cancer of the Kidney; Cancer of Kidney; Ovarian Cancer; Ovary Cancer; Cancer of the Ovary; Cancer of Ovary

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events

  30 days after completion of treatment (estimated to be 7 months)

• Overall Disease Control Rate of Intracranial Disease

  Completion of treatment (estimated to be 6 months)

• Overall Response Rate of Extracranial Disease

  Completion of treatment (estimated to be 6 months)

• Overall Disease Control Rate of Extracranial Disease

  Completion of treatment (estimated to be 6 months)

• Overall Response Rate Considering Both Intracranial and Extracranial Disease

  Completion of treatment (estimated to be 6 months)

Study Arms (3)

Cohort A: Non-small cell lung cancer w/o corticosteroids

EXPERIMENTAL

-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.

Drug: MEDI4736

Cohort B: Epithelial origin solid tumors w/o corticosteroids

EXPERIMENTAL

-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.

Drug: MEDI4736

Cohort C: NSCLC or non-NSCLC w/corticosteroids

EXPERIMENTAL

-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.

Drug: MEDI4736

Interventions

MEDI4736 DRUG

Also known as: Durvalumab

Cohort A: Non-small cell lung cancer w/o corticosteroids; Cohort B: Epithelial origin solid tumors w/o corticosteroids; Cohort C: NSCLC or non-NSCLC w/corticosteroids

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• AstraZeneca: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Breast Neoplasms; Pancreatic Neoplasms; Colorectal Neoplasms; Kidney Neoplasms; Ovarian Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Gonadal Disorders

Results Point of Contact

• Title: Ramaswamy Govindan, M.D.
• Organization: Washington University School of Medicine

rgovindan@wustl.edu

314-362-5737

Study Officials

• Ramaswamy Govindan, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2016
• First Posted: February 1, 2016
• Study Start: September 12, 2016
• Primary Completion: September 21, 2017
• Study Completion: January 11, 2018
• Last Updated: November 6, 2018
• Results First Posted: October 10, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)