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

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ClinicalTrials.gov Identifier: NCT03406715
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : June 5, 2019
Sponsor:
Collaborators:
Bristol-Myers Squibb
MultiVir, Inc.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief 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.


Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Lung Cancer Relapsed Small Cell Lung Cancer Drug: Nivolumab Drug: Ipilimumab Biological: Dendritic Cell based p53 Vaccine Phase 2

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).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 29, 2018
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Combination Immunotherapy Plus Vaccine
Combination 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.
Drug: Nivolumab
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.
Other Name: BMS-936558

Drug: Ipilimumab
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.
Other Name: Yervoy®

Biological: Dendritic Cell based p53 Vaccine
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).
Other Name: Ad.p53-DC




Primary Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: Up to 3 years ]
    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 :
  1. Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]
    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.

  2. Overall Survival (OS) [ Time Frame: Up to 3 years ]
    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.

  3. Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
    Overall response rate (ORR=CR+PR) will be summarized using both point estimates and exact confidence intervals based on the binomial distribution by group.

  4. Immune Response (IR) [ Time Frame: Up to 3 years ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03406715


Locations
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United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Germaine Gonzalez-Vazquez    813-745-6636    germaine.gonzalezvazquez@moffitt.org   
Contact: Alberto Chiappori, M.D.    813-745-3050    alberto.chiappori@moffitt.org   
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bristol-Myers Squibb
MultiVir, Inc.
Investigators
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Principal Investigator: Alberto Chiappori, M.D. H. Lee Moffitt Cancer Center and Research Institute

Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT03406715     History of Changes
Other Study ID Numbers: MCC-19163
CA209-9KN ( Other Identifier: Bristol-Myers Squibb Protocol Number )
MVIR-Adp53DC-001 ( Other Identifier: MultiVir, Inc. Protocol Number )
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
SCLC
Lung Cancer
Lung Disease
Relapsed SCLC
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Ipilimumab
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents