ClinicalTrials.gov
ClinicalTrials.gov Menu

Anti‐PD 1 Brain Collaboration for Patients With Melanoma Brain Metastases (ABC)

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02374242
Recruitment Status : Active, not recruiting
First Posted : February 27, 2015
Last Update Posted : April 11, 2018
Sponsor:
Collaborators:
Australia and New Zealand Melanoma Trials Group
Bristol-Myers Squibb
Information provided by (Responsible Party):
Melanoma Institute Australia

Brief Summary:

The purpose of this research project is to test the effectiveness of nivolumab versus nivolumab together with ipilimumab for the treatment of melanoma brain metastases.

Patients are eligible to join this study if they are aged 18 years or above and have been diagnosed with melanoma with brain metastases.


Condition or disease Intervention/treatment Phase
Melanoma Brain Metastases Drug: Nivolumab Drug: Ipilimumab Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Nivolumab and Nivolumab Combined With Ipilimumab in Patients With Melanoma Brain Metastases
Actual Study Start Date : November 4, 2014
Actual Primary Completion Date : September 4, 2017
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Active Comparator: Cohort 1 Nivolumab Monotherapy
Nivolumab 3mg/kg every 2 weeks, until disease progression, withdrawn consent, unacceptable toxicity or death.
Drug: Nivolumab
Nivolumab is a fully human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor PD‐1 (programmed death‐1 or programmed cell death‐1/PCD‐1) with immunopotentiation activity.
Other Names:
  • Opdivo
  • BMS-936558

Active Comparator: Cohort 2 Nivolumab Monotherapy
Nivolumab 3mg/kg every 2 weeks, until disease progression, withdrawn consent, unacceptable toxicity or death.
Drug: Nivolumab
Nivolumab is a fully human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor PD‐1 (programmed death‐1 or programmed cell death‐1/PCD‐1) with immunopotentiation activity.
Other Names:
  • Opdivo
  • BMS-936558

Active Comparator: Cohort 3 Nivolumab and Ipilimumab
Nivolumab 1mg/kg every 3 weeks x four doses and ipilimumab 3mg/kg every 3 weeks x four doses. After 12 weeks, nivolumab 3mg/kg alone every 2 weeks until disease progression, withdrawn consent, unacceptable toxicity or death.
Drug: Nivolumab
Nivolumab is a fully human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor PD‐1 (programmed death‐1 or programmed cell death‐1/PCD‐1) with immunopotentiation activity.
Other Names:
  • Opdivo
  • BMS-936558

Drug: Ipilimumab
Ipilimumab is a recombinant, human monoclonal antibody that binds to the cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4). CTLA‐4 is a negative regulator of T‐cell activation. Ipilimumab binds to CTLA‐4 and blocks the interaction of CTLA‐4 with its ligands, CD80/CD86. Blockade of CTLA‐4 has been shown to augment T‐cell activation and proliferation. The mechanism of action of ipilimumab's effect in patients with melanoma is indirect, possibly through T‐cell mediated anti‐tumour immune responses.
Other Names:
  • Yervoy
  • BMS-734016




Primary Outcome Measures :
  1. Intracranial response rate [ Time Frame: Approximately 3 years ]
    Proportion of patients with a complete or partial response in intracranial metastases as measured using RECIST 1.1 criteria (modified for brain metastases - bm RECIST), from week 12.


Secondary Outcome Measures :
  1. Extracranial response rate [ Time Frame: Approximately 3 years ]
    Proportion of patients with an overall complete or partial response in extra cranial metastases as measured using bm RECIST.

  2. Overall response rate [ Time Frame: Approximately 3 years ]
    Proportion of patients with an overall complete or partial response as measured using bm RECIST 1.1 criteria.

  3. Progression free survival in intracranial disease [ Time Frame: Approximately 3 years ]
    Time from the baseline assessment to the date of intracranial progression as measured using bm RECIST 1.1 criteria.

  4. Progression free survival in extracranial disease [ Time Frame: Approximately 3 years ]
    Time from the baseline assessment to the date of extracranial progression as measured using bm RECIST 1.1 criteria.

  5. Overall progression free survival [ Time Frame: Approximately 3 years ]
    Time from the baseline assessment to the date of local or distant progression as measured using bm RECIST 1.1 criteria. Patients dying from causes other than melanoma or treatment related toxicity will be censored at date of death. Patients alive without progression or with second primary cancers will be censored at date of last assessment.

  6. Overall survival [ Time Frame: Up to approximately 5 years ]
    Time from commencing study treatment to the date of death from any cause. Patient still alive will be censored at the date of last assessment.

  7. Safety and tolerability of nivolumab and nivolumab + ipilimumab (verse events by type, frequency and severity using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.) [ Time Frame: Approximately 3 years ]

    Description of adverse events by type, frequency and severity using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

    Number of patients who withdraw from the study due to intolerable adverse reactions.


  8. Patient rated quality of life [ Time Frame: Approximately 3 years ]
    The mean change from baseline quality of life scores at the time of clinical response, stable disease and progression in each cohort.

  9. Clinical response using immune related response criteria (irRC) [ Time Frame: Approximately 3 years ]
    Proportion of patients with an intracranial, extracranial and overall complete or partial response, stable disease or progression and progression free survival as measured using immune‐related response criteria (irRC) and the proportion of concordant or discordant results compared with bm RECIST.

  10. Tissue and blood biomarkers of response and progression [ Time Frame: Approximately 3 years ]
    PD‐L1 status, immune markers and genetics of response and resistance in tumour tissue at baseline and at disease progression. Lymphocyte, T cell subsets, myeloid derived suppressor cells and other biomarkers in blood at baseline, after 2 weeks on study treatment and then every 6 weeks, to examine if any specific subsets are predictive or response or progression.

  11. FET‐PET response in the brain at 6 and 12 weeks on therapy (Proportion of patients with a lower standardised uptake value from baseline in intracranial metastases, following at least ONE dose of study treatment) [ Time Frame: Approximately 1 year ]
    Comparison of FET‐PET to MRI findings. Proportion of patients with a lower standardised uptake value from baseline in intracranial metastases, following at least ONE dose of study treatment(s).



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.


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

Cohort 1 and 3

Inclusion Criteria:

  1. ≥18 years of age.
  2. Written informed consent
  3. AJCC Stage IV (any T, any N, M1c) histologically confirmed melanoma or unknown primary melanoma. Patients must have at least 1 radiological definitive brain metastasis that is ≥ 5mm and ≤40mm measurable per RECIST version 1.1 guidelines.
  4. In patients with prior BRAF inhibitor treatment, intracranial disease progression must be demonstrated (RECIST >20% or new measurable brain metastases) compared with nadir of intracranial response during BRAF inhibitor treatment, and confirmed with a second MRI brain scan at any time from the beginning of the drug washout period (dabrafenib=5 days, trametinib=14 days).
  5. No prior localised treatment for brain metastases (eg. surgery or radiotherapy).
  6. Neurologically asymptomatic from brain metastases.
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0‐2, and life expectancy > 30 days.
  8. Able to undergo MRI with Gadolinium contrast agent.
  9. Adequate haematological, hepatic and renal organ function.
  10. Women of childbearing potential: negative serum pregnancy test and effective contraception from 14 days prior to study treatment until 23 weeks after the last dose.
  11. Men with female partner of childbearing potential to use effective contraception from 14 days prior to study treatment until 31 weeks after the last dose.

    Exclusion Criteria:

  12. Any melanoma brain metastasis >40mm.
  13. Ocular melanoma.
  14. Prior treatment with an anti‐PD‐1 or anti‐PD‐L1 , anti‐PD‐L2, anti‐CD137, or anti‐CTLA‐4 antibody, or any other antibody or drug specifically targeting T‐cell co‐stimulation or checkpoint pathways.
  15. Patients with active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  16. Current systemic treatment with corticosteroids, except prednisone at nonimmunosuppressive doses of ≤ 10 mg/day (or equivalent). Past treatment for non‐neurological symptoms allowed, if ceased 2 weeks prior to starting study treatment. Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if patient on a stable dose. Non‐absorbed intraarticular steroid injections will be permitted.
  17. Any investigational drug or other systemic drug therapy for melanoma within 28 days or 5 half‐lives from baseline.
  18. Known to be HIV positive, or a positive test for hepatitis B and C .
  19. Another malignancy or concurrent malignancy unless disease‐free for 3 years.
  20. Serious or unstable pre‐existing medical conditions or other conditions that could interfere with the patient's safety, consent, or compliance.
  21. Pregnant or breastfeeding females.
  22. Administration of any form of live vaccination (such as influenza vaccine) within 30 days of starting trial and anticipated use during the trial. Administration of any other vaccine is cautionary within 30 days of starting the trial and during the trial.

Cohort 2 ‐ per Cohorts 1 & 3, except patients must have at least one of the following:

  1. Failed prior local therapy for brain metastases (including surgery, stereotactic radiotherapy or whole brain radiotherapy) where disease has progressed per RECIST (>20% increase in SOD or new measurable brain metastases),

    and/or;

  2. Have current neurological symptoms related to brain metastases. IF they have received prior local therapy for brain metastases, the disease must have progressed per RECIST (>20% increase in SOD or new measurable brain metastases),

    and/or;

  3. Have leptomeningeal disease concurrently with measurable brain metastases. IF they have had failed prior local therapy for brain metastases, this must have progressed per RECIST (>20% increase in SOD or new measurable brain metastases).

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): NCT02374242


Locations
Australia, New South Wales
Melanoma Institute Australia
North Sydney, New South Wales, Australia, 2060
Australia, Queensland
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
Sponsors and Collaborators
Melanoma Institute Australia
Australia and New Zealand Melanoma Trials Group
Bristol-Myers Squibb
Investigators
Study Chair: Georgina Long Melanoma Institute Australia

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Melanoma Institute Australia
ClinicalTrials.gov Identifier: NCT02374242     History of Changes
Other Study ID Numbers: CA209‐170
ACTRN12614001315606 ( Registry Identifier: Australian New Zealand Clinical Trials Registry )
ANZMTG 01.14 ( Other Identifier: Australian New Zealand Melanoma Trials Group )
First Posted: February 27, 2015    Key Record Dates
Last Update Posted: April 11, 2018
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Melanoma Institute Australia:
Brain
Metastases
Immunotherapy
Intracranial response
Nivolumab
Ipilimumab
Biomarkers
Immune related response criteria

Additional relevant MeSH terms:
Melanoma
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs