Trial record 5 of 15 for:    Recruiting, Enrolling by invitation Studies | Interventional Studies | Brain Tumor | United States | Phase Early Phase 1, 1, 2 | Start date from 02/15/2018 to 06/11/2018

A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

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. Identifier: NCT03425292
Recruitment Status : Recruiting
First Posted : February 7, 2018
Last Update Posted : October 10, 2018
Information provided by (Responsible Party):
Santosh Kesari, John Wayne Cancer Institute

Brief Summary:

The purpose of this study is to test the safety and tolerability of nivolumab or nivolumab plus ipilimumab when used following surgery and before standard therapy with radiation and temozolomide in patients with newly diagnosed glioblastoma.

Additional aims of the study are to:

  • Find out side effects (good and bad) of nivolumab and ipilimumab.
  • Evaluate any preliminary evidence of anticancer activity of nivolumab and ipilimumab.
  • Evaluate tumor characteristics by collecting brain tumor tissue samples.
  • Measure the amount of nivolumab and ipilimumab in biospecimens.
  • Look at biomarkers in biospecimens.

Condition or disease Intervention/treatment Phase
Newly Diagnosed Glioblastoma Drug: Temozolomide Radiation: conformal brain radiation therapy Drug: Nivolumab Drug: Ipilimumab Phase 1

Detailed Description:

Patients having a clinically planned surgical procedure (biopsy or cytoreduction) for a suspected diagnosis of glioblastoma will be approached for participation in this study. Tumor tissue obtained from surgery will be used for histological diagnosis and clinical molecular profiling, and excess tumor tissue will be collected for potential correlative studies. A small sample of blood and CSF for research will also be collected.

Once a diagnosis of glioblastoma is confirmed, the patient will be randomized 1:1:1 to Treatment Arm 1 standard of care (radiation + chemotherapy), Treatment Arm 2 (nivolumab), or Treatment Arm 3 (nivolumab + ipilimumab). Treatment will be started approximately 7-42 days following surgery once the patient has recovered from surgery. Routine clinical evaluations will be performed prior to treatment initiation and throughout treatment as clinically indicated. Radiographic brain imaging will be performed approximately 21-42 after treatment initiation and then routinely for medical management. Tumor response will be assessed according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) Working Group criteria.

Treatment may continue until the patient experiences unacceptable toxicity or clear disease progression. The determination of whether to stop treatment due to disease progression will be based on the investigator's evaluation of the patient's clinical and radiographic condition, taking into consideration the interpretation of localized inflammatory responses that can mimic radiographic features of tumor progress. Patients discontinuing treatment will be directed by their treating physician for the next step in their medical management - such as a clinically-indicated cytoreductive surgery, standard radiation chemotherapy if assigned to study arm 2 or 3, or a different treatment regimen. If another treatment is started, clinical evaluations and response assessments will continue as clinically-indicated; blood and CSF will be collected after the first month, then every three to six months.

Study Type : Interventional
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer
Actual Study Start Date : March 1, 2018
Estimated Primary Completion Date : February 1, 2019
Estimated Study Completion Date : February 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Brain Tumors

Arm Intervention/treatment
Active Comparator: Standard radiation plus temozolomide
Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide
Drug: Temozolomide
concomitant and adjuvant temozolomide
Other Name: temodar

Radiation: conformal brain radiation therapy
standard radiation therapy for newly diagnosed glioblastoma

Experimental: Nivolumab
Drug: Nivolumab
nivolumab 300 mg IV every 2 weeks
Other Name: opdivo

Experimental: Nivolumab plus ipilimumab
Nivolumab plus Ipilimumab
Drug: Nivolumab
nivolumab 300 mg IV every 2 weeks
Other Name: opdivo

Drug: Ipilimumab
ipilimumab 1 mg/kg IV every 6 weeks
Other Name: yervoy

Primary Outcome Measures :
  1. Rate of dose limiting toxicities [ Time Frame: first 28 days of treatment ]
    treatment-related adverse events that impact administration of treatment

Secondary Outcome Measures :
  1. Treatment-related adverse events [ Time Frame: approximately 7 months ]
    Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.

  2. Tumor response rates [ Time Frame: up to 5 years ]
    Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria.

  3. Progression free survival (PFS) [ Time Frame: up to 5 years ]
    The duration of time from start of treatment until objective tumor response.

  4. Overall survival (OS) [ Time Frame: up to 5 years ]
    The duration of time from start of treatment to death.

  5. Levels of nivolumab and ipilimumab in specimens [ Time Frame: approximately 4 months ]
    Nivolumab and/or ipilimumab levels in specimens.

  6. Change in clinical molecular profile of tumor tissue after treatment [ Time Frame: approximately 6 months to 1 year ]
    Comparison of tumor tissue molecular profile generated from before and after study treatment.

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Participant has the ability to understand and the willingness to provide a signed and dated informed consent form.
  • Participant has the willingness to comply with all study procedures and availability for the duration of the study.
  • Participant is being evaluated for a potential, or known, diagnosis of glioblastoma.
  • Participant is a candidate for brain surgery.
  • Participant is male or female, ≥ 18 years of age.
  • Participant has a Karnofsky Performance Status ≥ 60%:

Exclusion Criteria:

  • Participant has received prior anti-cancer treatment for glioblastoma.
  • Participant has a diagnosis of immunodeficiency or active autoimmune disease.
  • Participant is receiving chronic systemic steroid therapy in dosing exceeding 8 mg daily of dexamethasone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Note: This is assessed after surgery, prior to starting drug treatment.
  • Participant has received a live vaccine within 28 days prior to the first dose of study agent. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), typhoid vaccine, and intranasal influenza vaccines (e.g., FluMist®).
  • Participant has a severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study intervention (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements).
  • Participant is a female of childbearing potential who is pregnant or nursing.

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 identifier (NCT number): NCT03425292

Contact: Trial Team 310-829-8265
Contact: Jaya Gill, RN 310-582-7437

United States, California
John Wayne Cancer Institute Recruiting
Santa Monica, California, United States, 90404
Contact: Jaya Gill, RN    310-582-7437   
Principal Investigator: Santosh Kesari, MD, PhD         
Sponsors and Collaborators
John Wayne Cancer Institute
Principal Investigator: Santosh Kesari, MD, PhD John Wayne Cancer Institute

Responsible Party: Santosh Kesari, Professor, Neurosciences, John Wayne Cancer Institute Identifier: NCT03425292     History of Changes
Other Study ID Numbers: JWCI-17-0801
First Posted: February 7, 2018    Key Record Dates
Last Update Posted: October 10, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Santosh Kesari, John Wayne Cancer Institute:

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action