Clinical Trials /

Combination Immunotherapy-Ipilimumab-Nivolumab-Dendritic Cell p53 Vac - Patients With Small Cell Lung Cancer (SCLC)

NCT03406715

Description:

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.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Combination Immunotherapy-Ipilimumab-Nivolumab-Dendritic Cell p53 Vac - Patients With Small Cell Lung Cancer (SCLC)
  • Official Title: Combination Immunotherapy With Ipilimumab and Nivolumab Plus a Dendritic Cell Based p53 Vaccine (Ad.p53-DC) in Patients With Relapsed Small Cell Lung Cancer (SCLC)

Clinical Trial IDs

  • ORG STUDY ID: MCC-19163
  • SECONDARY ID: CA209-9KN
  • SECONDARY ID: MVIR-Adp53DC-001
  • NCT ID: NCT03406715

Conditions

  • Small Cell Lung Cancer
  • Lung Cancer
  • Relapsed Small Cell Lung Cancer

Interventions

DrugSynonymsArms
NivolumabBMS-936558Combination Immunotherapy Plus Vaccine
IpilimumabYervoy®Combination Immunotherapy Plus Vaccine
Dendritic Cell based p53 VaccineAd.p53-DCCombination Immunotherapy Plus Vaccine

Purpose

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.

Detailed Description

      During the Induction Immunotherapy phase (4 x 21 day cycles) of the study, participants will
      receive Ipilimumab and Nivolumab on Day 1 of each cycle for 4 cycles. Participants will
      receive the p53 vaccine on Days 1 and 15 of cycle 1 and then again on Day 8 of Cycle 2.

      Beginning on Day 1 of Cycle 5 participants will start Maintenance Immunotherapy. During this
      phase of the study, participants will receive Nivolumab only on Day 1 of every 4 week period.
      Participants will also receive the p53 vaccine three additional times (every 4 weeks over a
      12 week period). During Maintenance Immunotherapy you will continue to receive Nivolumab only
      on Day 1 of each additional 4 week period that you take part until your 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. During retreatment,
      participants would receive the combination of Ipilimumab and Nivolumab or Nivolumab alone
      every three weeks for a maximum of one additional year.

      P53 Vaccine production

      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).
    

Trial Arms

NameTypeDescriptionInterventions
Combination Immunotherapy Plus VaccineExperimentalCombination immunotherapy with Ipilimumab and Nivolumab plus a Dendritic Cell based p53 Vaccine (Ad.p53-DC). Induction Immunotherapy, followed by Maintenance Immunotherapy and potentially Retreatment. During retreatment, participants would receive the combination of Ipilimumab and Nivolumab or Nivolumab alone every three weeks for a maximum of one additional year.
  • Nivolumab
  • Ipilimumab
  • Dendritic Cell based p53 Vaccine

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease Control Rate (DCR)
Time Frame:Up to 3 years
Safety Issue:
Description:Response will be assessed primarily using the response evaluation criteria in solid tumors (RECIST v1.1). The immune related (ir)RECIST will also be used secondarily. DCR = Complete Response (CR) = Partial Response (PR) + Stable Disease (SD) rates. The disease control (DCR=CR+PR+SD) rates will be summarized using both point estimates and exact confidence intervals based on the binomial distribution by group.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description:The PFS, defined as time from enrollment (eligible date) to date of progression/death, whichever happens first, or censor at last clinical follow-up date. PFS will be summarized utilizing the K-M method.
Measure:Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:The OS, defined as the time from study enrollment (eligible date) to death from any cause. OS will be summarized utilizing the K-M method.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 3 years
Safety Issue:
Description:Overall response rate (ORR=CR+PR) will be summarized using both point estimates and exact confidence intervals based on the binomial distribution by group.
Measure:Immune Response (IR)
Time Frame:Up to 3 years
Safety Issue:
Description:Criteria used to determine the presence of immune responses: Individual participant will be considered responders if at any time point the response in IFN-γ ELISPOT assay is higher than 30 spots per 2 × 10^5 AND the response in IFN-γ ELISPOT to ALVAC p53 is more than 2 SD higher than the response to corresponding ALVAC control at the same time point AND 2 SD higher than the corresponding response at the base line (before start of the treatment).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • SCLC
  • Lung Cancer
  • Lung Disease
  • Relapsed SCLC

Last Updated

November 8, 2019