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Personalized Immunotherapy in Adults With Advanced Cancers Immunotherapy in Adults With Advanced Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03568058
Recruitment Status : Recruiting
First Posted : June 26, 2018
Last Update Posted : January 7, 2020
Sponsor:
Information provided by (Responsible Party):
Ezra Cohen, University of California, San Diego

Brief Summary:
The purpose of this study is to determine if it is possible to make and administer safely a 'personalized' vaccine to treat patients that have been diagnosed with advanced cancer and are not candidates for curative therapy.

Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: personalized vaccine Drug: Pembrolizumab Phase 1

Detailed Description:

The purpose of this study is to determine if it is possible to make and administer safely a 'personalized' vaccine to treat patients that have been diagnosed with advanced cancer and are not candidates for curative therapy.

This 'personalized' vaccine will use information gained from specific characteristics of your own cancer. It is known that cancer has mutations (changes in genetic material) that are specific to an individual and tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune (protective) responses, which may help your body fight any tumor cells that could cause your cancer to come back in the future. The study will examine the safety of the vaccine when given at several time points and will examine your blood cells for signs that the vaccine induced an immune response.

The personalized vaccine will be given in combination with an anti-PD1 antibody, pembrolizumab, which is used with the intention to increase anti-cancer immunity (protection). Pembrolizumab is a type of drug that blocks certain proteins made by some types of immune system cells, such as T cells, and some cancer cells. These proteins help keep immune responses in check and can keep T cells from killing cancer cells. When these proteins are blocked, the "brakes" on the immune system are released and T cells are able to kill cancer cells better.

This personalized vaccine is considered experimental because this is not an FDA approved therapy for cancer.

Pembrolizumab is FDA approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), classical Hodgkin lymphoma (cHL), urothelial carcinoma, microsatellite instability-high cancer (MSI-H), gastric cancer, cervical cancer, and hepatocellular carcinoma (HCC). Pembrolizumab is considered experimental (investigational) for the treatment of all other cancer types.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Safety and Feasibility Study of Personalized Immunotherapy in Adults With Advanced Cancers
Actual Study Start Date : July 26, 2018
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: vaccine and anti-PD-1
personalized vaccine and anti-PD-1 administered concurrently at the start of study therapy
Drug: personalized vaccine
Vaccine will be constructed for each subject that express multiple candidate tumor-derived neoantigens.

Drug: Pembrolizumab
200 mg pembrolizumab will be administered intravenous (IV) infusion every 3 weeks.
Other Name: keytruda

Experimental: anti-PD1 before vaccine
anti-PD-1 antibody for 6 weeks followed by personalized vaccine therapy
Drug: personalized vaccine
Vaccine will be constructed for each subject that express multiple candidate tumor-derived neoantigens.

Drug: Pembrolizumab
200 mg pembrolizumab will be administered intravenous (IV) infusion every 3 weeks.
Other Name: keytruda

Experimental: anti-PD1 and vaccine
anti-PD-1 antibody followed by personalized vaccine therapy
Drug: personalized vaccine
Vaccine will be constructed for each subject that express multiple candidate tumor-derived neoantigens.

Drug: Pembrolizumab
200 mg pembrolizumab will be administered intravenous (IV) infusion every 3 weeks.
Other Name: keytruda

Experimental: vaccine
personalized vaccine therapy
Drug: personalized vaccine
Vaccine will be constructed for each subject that express multiple candidate tumor-derived neoantigens.




Primary Outcome Measures :
  1. Quantitative frequency of TCR [ Time Frame: 1 year ]
  2. Number of Participants with Treatment-related Adverse Events [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Overall Response [ Time Frame: 1 year ]
    RECIST 1.1

  2. Progression-free survival (PFS) [ Time Frame: 1 year ]
    Duration of time from start of study treatment until objective tumor progression or death.

  3. Time to Progression [ Time Frame: 1 year ]
    Duration of time from start of study treatment until objective tumor progression.

  4. Overall Survival [ Time Frame: 1 year ]
    Duration of time from start of study treatment to death



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

  • Histologically or cytologically documented incurable solid tumor [excluding lymphoma].
  • Measurable disease as defined by RECIST 1.1
  • Progressed on or be intolerant to therapies that are known to provide clinical benefit.
  • Non-measurable disease by RECIST 1.1 and high-risk (>50% over 5 years) of mortality
  • At least one tumor site accessible for biopsy.
  • Adequate organ function
  • Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.

Exclusion Criteria

  • Currently receiving or has received another anti-cancer therapy within 4 weeks prior to first dose of vaccine study treatment.
  • Currently receiving or has received PD1/PDL1 inhibitor immunotherapy within 4 weeks prior to first dose of study treatment.
  • Currently receiving or has received anti-PD1 or anti-CTLA4 treatment during the vaccine preparation period.
  • Receiving TNF pathway inhibitors, PI3 kinase inhibitors, systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of study medication.
  • Received an investigational agent within 28 days prior to the first dose of study drug.
  • Untreated brain metastases; individuals with treated and stable metastases are eligible. Eligible subjects should have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for brain metastases for at least 4 weeks and are neurologically stable for 8 weeks (confirmed by MRI) prior to administration of experimental therapy
  • Has known history of Human Immunodeficiency Virus (HIV).
  • Received a diagnosis of hepatitis B or hepatitis C for which there is no clear evidence of natural immunity, immunity subsequent to vaccination, or successful eradication of the virus following antiviral therapy (individuals who are hepatitis C antibody positive may be enrolled if negative viral load confirmed).
  • History of autoimmune disease including: inflammatory bowel disease (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g. Wegener's granulomatosis); central nervous system or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barré syndrome, myasthenia gravis, multiple sclerosis). Individuals with vitiligo, Sjogren's Syndrome, interstitial cystitis, Graves' or Hashimoto's Disease, celiac disease, DM1, or hypothyroidism stable on hormone replacement will be allowed with Study Medical Monitor's approval.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • History of receiving a solid organ transplant or allogeneic bone marrow transplant.
  • Major surgical procedure within 28 days prior to the first dose of study drug.
  • If female, pregnant or breastfeeding.

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): NCT03568058


Contacts
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Contact: Ezra Cohen 858-534-6161 ecohen@health.ucsd.edu
Contact: Elaine Eng e1eng@health.ucsd.edu

Locations
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United States, California
UCSD Medical Center Recruiting
San Diego, California, United States, 92103
Contact: Amanda Natsuhara       anatsuha@health.ucsd.edu   
Contact: Khushbu Singh    (858) 246-2604    ksingh@health.ucsd.edu   
Principal Investigator: Ezra Cohen, MD         
Sponsors and Collaborators
Ezra Cohen
Investigators
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Principal Investigator: Erza Cohen, MD University of California, San Diego
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Responsible Party: Ezra Cohen, Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT03568058    
Other Study ID Numbers: 180410
First Posted: June 26, 2018    Key Record Dates
Last Update Posted: January 7, 2020
Last Verified: January 2020

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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 Ezra Cohen, University of California, San Diego:
immunotherapy
personalized cancer vaccine
personalized immunotherapy
pembrolizumab
Keytruda
cancer
neoantigen
solid tumor
vaccine
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents