Combination Immunotherapy-Ipilimumab-Nivolumab-Dendritic Cell p53 Vac - Patients With Small Cell Lung Cancer (SCLC)
Condition: Small Cell Lung Cancer; Lung Cancer; Relapsed Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Nivolumab; Ipilimumab; Dendritic Cell based p53 Vaccine
Intervention description: Nivolumab (BMS-936558) is an anti-PD-1 antibody. It works by attaching to and blocking a molecule called PD-1. Induction Immunotherapy Phase (4 x 21 days cycles): Nivolumab on Day 1 of each cycle for 4 cycles. Maintenance Immunotherapy beginning on Day 1 of Cycle 5: Nivolumab only on Day 1 of every 4 week period. Participants will continue to receive Nivolumab only on Day 1 of each additional 4 week period that they take part until their disease progresses. The Retreatment phase of the study may be available to participants whose doctor feels they would benefit from retreatment and if they qualify for this retreatment.; Ipilimumab is an antibody (a type of human protein) that is approved to treat patients with metastatic melanoma. In this study, the use of ipilimumab is investigational. Induction Immunotherapy Phase (4 x 21 days cycles): Ipilimumab on Day 1 of each cycle for 4 cycles. The Retreatment phase of the study may be available to participants whose doctor feels they would benefit from retreatment and if they qualify for this retreatment.; Dendritic Cell based p53 Vaccine (Ad.p53-DC). The p53 vaccine will be made by inserting the p53 gene (a gene is a hereditary unit of all living organism within a cell) into a subset of the participant's own white blood cells. The insertion of the gene into their white blood cells will occur in the laboratory, after their cells have been extracted from their body through a procedure called leukopheresis (similar to dialysis). Induction Immunotherapy Phase (4 x 21 day cycles): Participants will receive the p53 vaccine on Days 1 and 15 of cycle 1 and then again on Day 8 of Cycle 2. Maintenance Immunotherapy beginning on Day 1 of Cycle 5: p53 vaccine three additional times (every 4 weeks over a 12 week period).
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SCLC; Lung Cancer; Lung Disease; Relapsed SCLC

Summary:

      The purpose of this study is to find out what effects (good and bad) immunotherapy treatment
      using the p53 vaccine (Ad.p53-DC) in combination with Nivolumab and Ipilimumab has on small
      cell lung cancer. Immunotherapy is a cancer therapy that uses the body's immune system to
      fight cancer cells.

      This study can be divided into three different phases: initial Induction Immunotherapy,
      Maintenance Immunotherapy and Retreatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic or cytologic diagnosis of SCLC

          -  Recurrence to at least one prior treatment with a platinum containing regimen
             (cisplatin or carboplatin) including limited stage (LS) and extensive stage (ES)
             initial presentations. Note: In patients with SCLC the most frequent platinum
             containing doublet used is etoposide-carboplatin. However, etoposide-cisplatin and
             irinotecan or topotecan combined with either carboplatin or cisplatin are platinum
             doublet regimens that can sometimes be used and thus would be allowed for the purposes
             of trial enrollment and eligibility.

          -  Excluded are patients who upon relapse may be still considered for a salvage
             concurrent chemo-radiation approach.

          -  Willing and able to provide written informed consent/assent for the trial.

          -  Be 18 years of age or older on day of signing informed consent

          -  Have measurable disease based on Response Evaluation in Solid Tumors (RECIST) 1.1

          -  Have a performance status of 0 - 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale

          -  Demonstrate adequate organ function. All screening labs should be performed within 30
             days of treatment initiation.

          -  Life expectancy of >4 months.

          -  Favorable tumor p53 biomarker profile defined by ≥ 50% p53 positive tumor cells by
             immunohistochemistry. Tumor p53 biomarker evaluations may be performed with either
             original or recurrent tumor although samples from recurrent disease are preferred.

          -  Females of childbearing potential should have a negative urine or serum pregnancy
             within 72 hours prior to receiving the first dose of study medication. If the urine
             test is positive or cannot be confirmed as negative, a serum pregnancy test will be
             required.

          -  Females of childbearing potential should be willing to use 2 methods of birth control
             or be surgically sterile, or abstain from heterosexual activity for the course of the
             study through 120 days after the last dose of study medication.

          -  Males should agree to use an adequate method of contraception starting with the first
             dose of study therapy through 120 days after the last dose of study therapy.

        Exclusion Criteria:

          -  Currently participating and receiving study therapy or has participated in a study of
             an investigational agent and received study therapy or used an investigational device
             within 4 weeks of the first dose of treatment.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid or any other form
             of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
             Therapy: Systemic steroid doses of less than 10 mg of prednisone daily or its
             equivalent are allowed in patients receiving physiologic replacement steroid doses for
             both criteria 2 and 8.

          -  Has a known history of active Bacillus Tuberculosis (TB)

          -  Hypersensitivity to Ipilimumab and/or nivolumab or any of its excipients.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) excluding any anti-PD-1 and/or
             anti-PD-L1 checkpoint inhibitor within 4 weeks prior to study Day 1 or who has not
             recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
             baseline) from adverse events due to a previously administered agent. - Note:
             Potential participants with ≤ Grade 2 neuropathy are an exception to this criterion
             and may qualify for the study. - Note: If potential participant received major
             surgery, they must have recovered adequately from the toxicity and/or complications
             from the intervention prior to starting therapy.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer. Other
             malignancies that remain without evidence of disease or recurrence, 2 years or more
             after curative therapy are also considered part of this exception.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Patients with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least 2 weeks prior
             to the first dose of trial treatment and any neurologic symptoms have returned to
             baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          -  Any diagnosis of autoimmune disease (confirmed by medical records or appropriate
             laboratory testing)

          -  Known history of, or any evidence of active, non-infectious pneumonitis.

          -  Has an active infection requiring systemic therapy

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the trial, interfere with participation for the full
             duration of the trial, or is not in the best interest of the person to participate, in
             the opinion of the treating investigator.

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial.

          -  Pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)

          -  Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected)

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.

          -  Excluded are patients who upon relapse may be still considered for a salvage
             concurrent chemo-radiation approach