To Immunize Patients With Extensive Stage SCLC Combined With Chemo With or Without All Trans Retinoic Acid
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Paclitaxel; Drug: Ad.p53-DC vaccines; All -trans Retinoic Acid (ATRA)
Intervention description: All groups wil receive paclitaxel as second line chemotherapy if their cancer spreads. At any point when a patient develops evidence of progressive disease, the patient will be treated with second-line chemotherapy. Paclitaxel will be given at a dose of 200 mg/m² on day 1 of 21 day cycles.; Patients randomized to Arm B will receive vaccinations on 3 occasions, at 2 week intervals. 1-5x106 p53 positive DCs in 1 ml will be injected intradermally into 4 separate sites (0.25 ml injected at each site), in bilateral proximal upper and lower extremities (in the regions of the axillary and inguinal nodal basins). Patients will be restaged approximately 2-3 weeks after vaccine # 3 (first vaccine course). If patients show no sign of disease progression at restaging, then a second leukopheresis will be performed. Patients will then be vaccinated 3 more times (second vaccine course) at 4-week intervals, for a total of 6 possible vaccines. Restaging will occur 2-4 weeks after completing the second vaccine course. Patients in Arm C will receive vaccines at the same dose and schedule as described for patients in Arm B. In addition, they will receive 150 mg/m² of ATRA for 3 days prior to each vaccine administration (followed by vaccine administration on the fourth day).; The patients in Arm C will receive vaccines at the same dose and schedule as described for patients in Arm B. In addition, they will receive 150 mg/m² of ATRA for 3 days prior to each vaccine administration (followed by vaccine administration on the fourth day).
Intervention MeSH terms: Paclitaxel; Tretinoin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SCLC; vaccine; immunize

Summary:

      The purpose of this research study is to test a tumor (cancer) vaccine given along with
      chemotherapy to determine if this vaccine will increase the chances of the tumor shrinking
      and/or the amount of time that people who have this disease will live.
    

Eligibility criteria:

        Inclusion Criteria at the time of initial registration:

          -  Patients must have a histological confirmed diagnosis of Small Cell Lung Cancer (SCLC)

          -  Must have extensive stage SCLC

          -  Must have completed first line chemotherapy: 4-6 cycles of a standard
             platinum/etoposide regimen and PCI if chosen at the discretion of the treating
             Oncologist

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Acceptable (adequate) organ function including:

               -  White blood count (WBC) >2,500/mm³ and Absolute neutrophil count (ANC) >1,200/mm³

               -  Platelets > 75,000/mm³

               -  Hematocrit > 24% OR Hemoglobin ≥8.5g/dl

               -  Bilirubin < 2.0 mg/dl

               -  Creatinine < 2.0 mg/dl

               -  Aspartic transaminase (AST/SGOT) ≤2 x upper limit of normal (ULN)

               -  Alkaline phosphatase ≤3 x ULN

          -  Patients must have achieved responsive or non-progressive disease status (stable
             disease [SD], partial response [PR], or complete response [CR]) assessed 4-6 weeks
             after the last cycle of first line chemotherapy. SD, PR or CR may be confirmed after
             completion of prophylactic cranial irradiation (PCI) at the discretion of the
             principal investigator (PI) after discussion with the treating oncologist.

          -  Males and Females of reproductive potential must agree to use effective contraception
             during the study and for at least 4 weeks after the last dose of ATRA. Patients are
             instructed and agree to notify the principal investigator should a pregnancy occur for
             themselves or their partner.

          -  Willing and able to sign written informed consent and be able to comply with the study
             protocol for the duration of the study

        Exclusion Criteria at the time of initial registration:

          -  Patients with severe, uncontrolled intercurrent illness or infection

          -  Anticipated requirement for systemic chronic steroid use at the time of vaccination,
             unless specifically indicated for dose supplementation or replacement of established
             corticosteroid insufficiency

          -  Receiving systemic doses of corticosteroids should have them discontinued ≥ 2 weeks
             prior to starting vaccination (this include patients receiving steroids with PCI).
             Inhaled steroids should also be discontinued if at all possible. Chronic, stable doses
             of inhaled steroids for the treatment of chronic obstructive pulmonary disease (COPD),
             etc. are allowed if in the opinion of the treating physician(s) they cannot be
             stopped.

          -  Any pre-existing immunodeficiency condition, or a known history of human
             immunodeficiency virus (HIV), Hepatitis B or Hepatitis C

          -  Uncontrolled and/or symptomatic central nervous system (CNS) metastasis

          -  Pregnant or lactating women. A pregnancy test-serum Beta human chorionic gonadotropin
             (bHCG) will be obtained during the screening process.

          -  Have received any chemotherapy other than the first line chemotherapy specified in the
             study protocol: standard platinum/etoposide regimen

          -  Have received any prior investigational drugs including immunotherapy, gene therapy,
             hormone therapy, biologic therapy for treatment of SCLC

          -  Any known pre-existing autoimmune disorder

          -  History of a second malignancy within the previous 3 years. Exceptions include:
             non-melanoma skin cancers, any in-situ carcinomas and successfully treated early stage
             malignancies without evidence of recurrence for > 18 months.

          -  Have not recovered from any chemotherapy-related or other therapy-related toxicity at
             study entry

          -  Have had major surgery without full recovery or major surgery within 3 weeks of the
             start of vaccine treatment

          -  Patients with other significant diseases or disorders that, in the Investigator's
             opinion, would exclude them from the study

        Pre-Pheresis Criteria:

          -  Patients must have had a successful harvest of peripheral blood mononuclear cell
             (PBMC) with leukopheresis at least 6-10 weeks after chemotherapy.

          -  ECOG performance status of 0-2

          -  The last dose of first line chemotherapy must have been administered at least 4 weeks
             prior to the first vaccine administration.

          -  Patients who received radiation therapy: last dose of radiation must have been
             completed at least 2 weeks prior to the first vaccine administration and the patient
             must have recovered from the toxic effects of the treatment prior to study enrollment
             (except for alopecia)

          -  Patients who received steroid therapy: last steroid dose must have been given at least
             2 weeks prior to the first vaccine administration

          -  Adequate organ function:

               -  WBC > 2,500/mm³ and ANC >1,200/mm³

               -  Platelets > 75,000/mm³

               -  Hematocrit > 25%

               -  Hemoglobin ≥9g/dl

               -  Bilirubin < 2.0 mg/dl

               -  Creatinine < 2.0 mg/dL

               -  AST/SGOT ≤ 2 x ULN

               -  Alkaline phosphatase < 3 x ULN

          -  Patients must have signed informed consent at initial registration.

          -  HLA-A*0201 Testing as determined by flow cytometry followed by molecular analysis of a
             peripheral blood specimen, however this result will not be an inclusion criterion

        Pre-Paclitaxel Eligibility:

          -  Progressive disease after observation (Arm A) or vaccinations (Arms B and C)

          -  ECOG performance status of 0-2

          -  Adequate organ function:

               -  WBC > 2,500/mm³ and ANC >1,200/mm³

               -  Platelets > 75,000/mm³

               -  Hematocrit > 25%

               -  Hemoglobin ≥9g/dl

               -  Bilirubin < 2.0 mg/dl

               -  Creatinine < 2.0 mg/dL

               -  AST/SGOT ≤ 2 x ULN

               -  Alkaline phosphatase < 3 x ULN