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

• ClinicalTrials.gov Identifier: NCT03638765
• Recruitment Status: Unknown
• First Posted: August 20, 2018
• Last Update Posted: August 20, 2018
• Sponsor: Northwest Biotherapeutics
• Collaborator: Mayo Clinic
• Information provided by (Responsible Party): Northwest Biotherapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Brain Metastases; Lung Cancer Metastatic; Breast Cancer Metastatic	Biological: DCVax-Direct	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: November 2018
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. tumor response [ Time Frame: Every 8 weeks through study completion, an average of 6 months ]
   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
2. intracranial recurrence rate [ Time Frame: Every 8 weeks through study completion, an average of 6 months ]
   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
3. overall survival [ Time Frame: Through study completion, an average of 6 months ]
   Time to death for each subject, measured from time of enrollment

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Marnix L Bosch, PhD; 2404979022; marnix@nwbio.com

Locations

United States, Florida

Mayo Clinic

Jacksonville, Florida, United States, 32224

Contact: Alfredo Quinones Hinojosa, MD 904-956-3435 Quinones-Hinojosa.Alfredo@mayo.edu

Contact: Ronald Reimer, MD 904-783-6591

Sub-Investigator: YanYan Lou, MD

Sub-Investigator: Saranya Chumsri, MD

Sub-Investigator: Kaisorn Chaichana, MD

Sub-Investigator: Steven Rosenfeld, MD

Sponsors and Collaborators

Northwest Biotherapeutics

Mayo Clinic

Investigators

• Principal Investigator: Alfredo Quinones Hinojosa, MB; Mayo Clinic

More Information

• Responsible Party: Northwest Biotherapeutics
• ClinicalTrials.gov Identifier: NCT03638765
• Other Study ID Numbers: 050811
• First Posted: August 20, 2018
• Last Update Posted: August 20, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Northwest Biotherapeutics:

immunotherapy; dendritic cells; brain metastases

Additional relevant MeSH terms:

Lung Neoplasms; Neoplasm Metastasis; Neoplasms, Second Primary; Brain Neoplasms; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases