Patient case: 70-year-old male with Lung cancer. Genetic variant: ERBB2 Amplification. Other conditions: Arthritis.

Clinical trial: Treatment of Chemotherapy Refractory Human Epidermalgrowth Factor Receptor-2( HER-2) Positive Advanced Solid Tumors

Summary: RATINALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous T cells may make the body build immune response to kill cancer cells.
  PURPOSE: This clinical trial is to study genetically engineered lymphocyte therapy in treating patients with HER-2 positive advanced solid tumors,such as breast cancer, gastric cancer, hepatic carcinoma, endometrial cancer and ovary cancer.

Detailed description: PRIMARY OBJECTIVES:
  I.Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with anti-HER-2 vector(referred to as CART-HER-2 cells).
  II.Determine duration of in vivo survival of CART-HER-2 cells. RT-PCR(reverse transcription polymerase chain reaction)analysis of whole blood will be used to detect and quantify survival of CART-HER-2 TCR zeta:CD137 and TCR(T-cell receptor) zeta cells over time.
  SECONDARY OBJECTIVES:
  I.For patients with detectable diseases, measure anti-tumor response due to CART-HER-2 cell infusions.
  II.Estimate relative trafficking of CART-HER-2 cells in tumor bed.
  III.Determine if cellular or humoral host immunity develops against the murine anti-HER-2, and assess correlation with loss of detectable CART-HER-2(loss of engraftment).
  IV.Determine the relative subsets of CART-HER-2 T cells (Tcm,Tem,and Treg).
  OUTLINE: Patients are assigned to 1 group according to order of enrollment. Patients receive anti-HER-2-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of unacceptable toxicity.
  After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.
  Estimate relative trafficking of CART-HER-2 cells in peripheral blood.

Eligibility: Inclusion Criteria:
  -  Chemotherapy refractory HER-2-positive breast cancer, gastric cancer, non-small cell lung cancer, and chemotherapy resistant or relapsed ovary cancer.
  -  Relapsed patients after anti-HER-2 using antibody or kinase inhibitor therapy.
  -  Patients must be 18 years of age or older.
  -  Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2.
  -  Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters:
  Absolute neutrophil count greater than 1500/mm3. Platelet count greater than 100,000/mm3. Hemoglobin greater than 10g/dl (patients may receive transfusions to meet this parameter).
  Total bilirubin < 1.5 times upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2).
  -  Seronegative for HIV antibody.
  -  Seronegative for active hepatitis B, and seronegative for hepatitis C antibody.
  -  Patients must be willing to practice birth control during and for four months following treatment.NOTE:women of child-bearing age must have evidence of negative pregnancy test.
  -  Patients must be willing to sign an informed consent.
  Exclusion Criteria:
  -  Patients with life expectancy less than 12 months will be excluded.
  -  Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded.
  -  Patients with any of the following pulmonary function abnormalities will be excluded: FEV(forced expiratory volume), < 30% predicted; DLCO (diffusing capacity of lung for carbon monoxide) < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air.
  -  Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded.
  -  Pregnant and/or lactating women will be excluded.
  -  Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.
  -  Patients with any type of primary immunodeficiencies will be excluded from the study.
  -  Patients requiring corticosteroids (other than inhaled) will be excluded.
  -  Patients with history of T cell tumors will be excluded.
  -  Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.

Relevance to patient case: possibly relevant