Dendritic Cell Therapy for Brain Metastases From Breast- or Lung Cancer

A Phase Ib Clinical Trial Evaluating DCVax-Direct, Autologous Activated Dendritic Cells for Intratumoral Injection, in Patients With Unresectable Brain Metastases From Breast- or Non-Small Cell Lung Cancer

The study will use an Ommaya reservoir that drains into brain metastases to deliver activated, autolous dendritic cells to the tumor lesion, for patients who are 18 - 75 years old who have brain metastases from either lung cancer or breast cancer. The primary objective of the study is to evaluate the safety and feasibility of administering DCVax-Direct to patients with metastatic tumors in the brain. The secondary objectives are to determine tumor response, the rate of intracranial recurrence (IR), the rate of neurologic deaths, decline in neuro-cognitive functioning and overall survival. Approximately 10 patients with injectable metastatic brain tumors will be enrolled initially in a dose escalation scheme, with the expectation to enroll a total of 24 patients.

Study Overview

• Status: Unknown
• Conditions: Lung Cancer Metastatic; Brain Metastases; Breast Cancer Metastatic
• Intervention / Treatment: Biological: DCVax-Direct

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Willing and able to provide informed consent
2. Age between 18 and 75 years (inclusive) at screening.
3. Willingness to provide Social Security Number to facilitate survival follow up.
4. Pathologically confirmed metastatic breast or non-small cell lung cancer
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
6. Adequate bone marrow function, as indicated by the following:
7. Adequate renal function
8. Adequate liver function
9. Life expectancy > 12 weeks
10. Negative serum pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
11. Determined prior to enrollment: sufficient number of doses of DCVax-Direct manufactured to complete 7 injections. A second leukapheresis is allowed to meet this requirement if necessary.
12. Unequivocal evidence of newly diagnosed untreated brain metastases and/or progressive brain metastases after previous whole brain radiation therapy (WBRT), currently amenable to stereotactic radiosurgery
13. At least one CNS metastasis accessible for reservoir placement
14. At least one measurable CNS metastasis (lesion ≥ 10 mm per RANO-BM criteria)

Exclusion Criteria:

1. Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm OR Participated in a study of an investigational agent, received study therapy or used an investigational device ≤4 weeks prior to registration
2. Immunocompromised patients and patients with known immunodeficiency
3. Patients receiving systemic steroid therapy >10 mg prednisone or equivalent or any other immunosuppressive therapy ≤7 days prior to registration. NOTE: Inhaled steroids and low-dose corticosteroids are allowed.
4. History of active tuberculosis (TB), human immunodeficiency virus (HIV), active hepatitis B (e.g., HBsAg reactive) and/or active hepatitis C infection (e.g. HCV RNA qualitative is detected).
5. Active autoimmune disease requiring systemic treatment in the past 2 years (i.e. use of disease modifying agents, corticosteroids or immunosuppressive drugs). NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
6. Known history of, or any evidence of active, non-infectious pneumonitis.
7. Active infection requiring systemic therapy.
8. Other active malignancy ≤3 years prior to registration. EXCEPTIONS: Adequately treated non-melanotic skin cancer (adequate wound healing is required prior to study entry) or carcinoma-in-situ of the cervix. NOTE: If there is a history of prior solid tumor malignancy, it must have been treated curatively with no evidence of recurrence ≤3 years prior to registration.
9. Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
10. Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study.
11. Stage IV lung cancer patients with actionable EGFR, ALK or ROS-1 alteration will be excluded from the study.
12. Serious medical conditions
13. Any systemic myelotoxic chemotherapy within 8 weeks prior to screening
14. Evidence of recent hemorrhage on MR at pre-screening
15. Positive HIV-1, HIV-2, or HTLV-I/II tests.
16. History of multiple sclerosis
17. Requirement for ongoing immunosuppressants
18. Ongoing medical need for continuous anti-coagulation or anti-platelet medication,
19. Known genetic cancer-susceptibility syndromes such as Li-Fraumeni syndrome
20. Ongoing fever for longer than 48 hours of ≥ 101.5oF/38.6oC at screening
21. Females of child-bearing potential who are pregnant or lactating or who are not using adequate contraception.
22. Allergy or anaphylaxis to any of the reagents used in this study
23. Inability or unwillingness to return for required visits and follow-up exams

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Treatment; Intratumoral injection of activated, autologous dendritic cells (DCVax-Direct) in brain metastases from lung cancer or breast cancer	Biological: DCVax-Direct; activated, autologous dendritic cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety is assessed graded according to NCI CTC. The overall incidence of adverse events is calculated.	Toxicity is monitored and graded according to NCI CTC. The overall incidence of adverse events is calculated	Through study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor response	Tumor response is assessed through radiographic means and must at a minimum include MRI scans with and without contrast. The newly proposed iRANO criteria are used to characterize responses	Every 8 weeks through study completion, an average of 6 months
intracranial recurrence rate	Tumor recurrence in the brain is assessed through radiographic means and must at a minimum include MRI scans with and without contrast. The newly proposed iRANO criteria are used to characterize recurrences	Every 8 weeks through study completion, an average of 6 months
overall survival	Time to death for each subject, measured from time of enrollment	Through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Northwest Biotherapeutics
• Collaborators: Mayo Clinic
• Investigators: Principal Investigator: Alfredo Quinones Hinojosa, MB, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: August 15, 2018
• First Submitted That Met QC Criteria: August 17, 2018
• First Posted (Actual): August 20, 2018

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: August 17, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: immunotherapy; brain metastases; dendritic cells
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 050811

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No