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cMet CAR RNA T Cells Targeting Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01837602
Recruitment Status : Completed
First Posted : April 23, 2013
Last Update Posted : October 19, 2018
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE April 18, 2013
First Posted Date  ICMJE April 23, 2013
Last Update Posted Date October 19, 2018
Study Start Date  ICMJE April 2013
Actual Primary Completion Date August 13, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2013)
Number of Serious Adverse Event [ Time Frame: Two years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01837602 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE cMet CAR RNA T Cells Targeting Breast Cancer
Official Title  ICMJE Clinical Trial of Autologous cMet Redirected T Cells Administered Intratumorally in Patients With Breast Cancer
Brief Summary An open-label, clinical trial of autologous cMet redirected T cells administered intratumorally (IT) in patients with breast cancer. Fifteen evaluable patients will be enrolled in stepwise fashion. Step 1 will enroll patients with metastatic breast cancer refractory to at least 1 standard therapy, step 2 will include newly diagnosed patients with operable triple negative breast cancer.
Detailed Description This study is designed to determine the safety and feasibility of intratumoral administration of autologous T cells that have had genetic material transferred into the cell to redirect them to target breast cancer cells rather than their usual target. Eligible subjects will have metastatic breast cancer refractory to at least one standard therapy or to newly diagnosed with operable triple negative breast cancer.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Breast Cancer
  • Triple Negative Breast Cancer
Intervention  ICMJE Biological: cMet RNA CAR T cells
Study Arms  ICMJE Experimental: cMet positive breast cancer patients
Metastatic breast cancer patients with an accessible tumor (cutaneous, subcutaneous, or superficial) and/or a palpable adenopathy/mass, with ≥ 30% tumor cells expressing cMet as demonstrated on immunohistochemical analysis . The intensity for cMet IHC should be greater than or equal to 1+. The targeted tumor must be accessible (i.e. is not near a great vessel or the spinal cord) and can be surgically excised or biopsied.
Intervention: Biological: cMet RNA CAR T cells
Publications * Tchou J, Zhao Y, Levine BL, Zhang PJ, Davis MM, Melenhorst JJ, Kulikovskaya I, Brennan AL, Liu X, Lacey SF, Posey AD Jr, Williams AD, So A, Conejo-Garcia JR, Plesa G, Young RM, McGettigan S, Campbell J, Pierce RH, Matro JM, DeMichele AM, Clark AS, Cooper LJ, Schuchter LM, Vonderheide RH, June CH. Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer. Cancer Immunol Res. 2017 Dec;5(12):1152-1161. doi: 10.1158/2326-6066.CIR-17-0189. Epub 2017 Nov 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 17, 2018)
6
Original Estimated Enrollment  ICMJE
 (submitted: April 22, 2013)
15
Actual Study Completion Date  ICMJE August 13, 2018
Actual Primary Completion Date August 13, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Step 1 subjects only: metastatic breast cancer patients with an accessible tumor (cutaneous, subcutaneous, or superficial) and/or palpable adenopathy/mass. The targeted tumor is accessible (i.e. is not near a great vessel or the spinal cord) and can be surgically excised or biopsied.
  • Step 2 subjects only: Newly diagnosed, operable, triple negative breast cancer, i.e. ER/PR-negative, her2/neu-negative, with tumor size between 2 - 3 cm (T2) as measured by either clinical breast exam, mammogram, ultrasound or MRI, with or without ipsilateral axilla node involvement (N0 or N1).
  • cMet expression in ≥ 30% tumor cells as demonstrated on immuno-histochemistry analysis of archival slides. The intensity for cMet IHC should be greater than or equal to 1+. Punch biopsy or percutaneous core biopsy may be offered to Cohort 1 patients. To establish eligibility for patients in step 1, archival tumor tissues from any previously biopsied metastatic tumor deposit may be used for IHC staining. The metastatic tumor nodule to be targeted for IT injection may not necessarily be the same as previously biopsied metastatic site.
  • Age > 18 years old
  • Baseline Eastern Cooperative Oncology Group (ECOG) Clinical Performance Status 0 or 1
  • Adequate hematologic function:

WBC > 3.0 Plt > 75,000 Hgb > 10 g/dl Adequate renal function defined as serum creatinine < 1.5 times upper limit of normal

- Adequate hepatic function defined as: Total bilirubin < 1.5 times upper limit of normal, and ALT and AST < 2.5 times upper limit of normal

  • Women of child bearing potential must have a negative pregnancy test (blood or urine) and agree to use appropriate contraception from study screen through the duration of the trial. Men must agree to use appropriate contraception from IT injection through the duration of the trial.
  • Signed and dated written informed consent.

Exclusion Criteria:

  • Step 1 subjects only: Targeted tumor near a great vessel or spinal cord
  • Step 2 subjects only: Women already undergoing neoadjuvant chemotherapy to treat their primary triple negative breast cancer
  • Step 1 and 2 subjects:Positive for HIV-1/HIV-2
  • Active hepatitis B or hepatitis C infection
  • The anticipated use of the following within 2 weeks prior to apheresis and prior to planned IT T-cell injection:

Immunosuppressive drugs Cytotoxic chemotherapy (See Section 5.7 for complete details) Systemic glucocorticoids (steroid prep due to dye allergies prior to staging scans or use in anti-emetic prophylaxis for patients undergoing chemotherapy is allowed) Hematopoietic growth factors Other experimental therapy Note: Step 1 patients receiving non-investigational targeted therapy (lapatinib, trastuzumab, and/or pertuzumab) are eligible provided these medicines are at a stable dose and the patient began taking them more than 30 days prior to the planned IT T-cell injection.

  • Anticipated use of anti-coagulants such as coumadin, heparin, or Lovenox within 14 days before the planned IT T-cell injection RETIRED AS OF PROTOCOL VERSION 11
  • Pregnant women or nursing mothers
  • History of alcohol abuse or illicit drug use within 12 months of IT T-cell injection
  • Clinically significant comorbid disease or other underlying condition, including major autoimmune disorders that would contraindicate study therapy or confuse interpretation of study results
  • Significant psychiatric disorder and any other reason that in the Investigator's opinion would jeopardize protocol compliance or compromise the patient's ability to give informed consent.
  • Prior MI ascertained from medical history and review of systems
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01837602
Other Study ID Numbers  ICMJE UPCC 13111, 813858
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Julia Tchou, MD Abramson Cancer Center of the University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP