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

NCT03638765 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 050811
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Metastases; Lung Cancer Metastatic; Breast Cancer Metastatic

Keywords

immunotherapy; dendritic cells; brain metastases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• tumor response

  Every 8 weeks through study completion, an average of 6 months

• intracranial recurrence rate

  Every 8 weeks through study completion, an average of 6 months

• overall survival

  Through study completion, an average of 6 months

Study Arms (1)

Experimental Treatment

EXPERIMENTAL

Intratumoral injection of activated, autologous dendritic cells (DCVax-Direct) in brain metastases from lung cancer or breast cancer

Biological: DCVax-Direct

Interventions

DCVax-Direct BIOLOGICAL

activated, autologous dendritic cells

Experimental Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide informed consent
• Age between 18 and 75 years (inclusive) at screening.
• Willingness to provide Social Security Number to facilitate survival follow up.
• Pathologically confirmed metastatic breast or non-small cell lung cancer
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• Adequate bone marrow function, as indicated by the following:
• Adequate renal function
• Adequate liver function
• Life expectancy \> 12 weeks
• Negative serum pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
• 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.
• 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
• At least one CNS metastasis accessible for reservoir placement
• At least one measurable CNS metastasis (lesion ≥ 10 mm per RANO-BM criteria)

You may not qualify if:

• 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
• Immunocompromised patients and patients with known immunodeficiency
• 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.
• 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).
• 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.
• Known history of, or any evidence of active, non-infectious pneumonitis.
• Active infection requiring systemic therapy.
• 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.
• 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.
• 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.
• Stage IV lung cancer patients with actionable EGFR, ALK or ROS-1 alteration will be excluded from the study.
• Serious medical conditions
• Any systemic myelotoxic chemotherapy within 8 weeks prior to screening
• Evidence of recent hemorrhage on MR at pre-screening
• Positive HIV-1, HIV-2, or HTLV-I/II tests.

Sponsors & Collaborators

• Northwest Biotherapeutics: lead
• Mayo Clinic: collaborator

Study Sites (1)

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Alfredo Quinones Hinojosa, MB

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marnix L Bosch, PhD

CONTACT

2404979022; marnix@nwbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2018
• First Posted: August 20, 2018
• Study Start: November 1, 2018
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2020
• Last Updated: August 20, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)