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Metastatic MelanomaPhase 2NCT03728465

Evaluation of Safety and Efficacy of Patients With Four and More Symptomatic Brain Metastases of Melanoma

A Phase 2 study testing Nivolumab and Ipilimumab in people with Metastatic Melanoma and Brain Metastases, run by University Hospital Tuebingen at 11 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Up to 50% of patients with unresectable metastatic melanoma will develop brain metastases during their lifetime. A possible treatment options for patients with brain metastases are surgery and radiotherapy but usually for lesions in the range of < 3 brain metastases. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma, Brain Metastases
What is being tested?
Nivolumab and Ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
11 sitesGermany
Study dates
10 Apr 2018to 1 Jan 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent (ICF) prior to any screening procedures being performed
  • Ability to comply with protocol requirements
  • Metastatic histologically confirmed melanoma that is unresectable
  • Presence of > 3 active brain metastases confirmed/evaluated by MRI
  • Measurable disease by MRI per iRANO and RECIST 1.1 criteria
  • The time between the baseline MRI and the date of registration should not exceed 28 days. Steroid treatment is permissible before brain MRI evaluation but the dose should have been stable for at least 7 days and should be carefully documented
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  • Patient must agree to the cerebro-spinal fluid (CSF) collections according to the study protocol
  • Patients naïve for systemic treatment are eligible
  • Patients pretreated with systemic immunotherapy, targeted therapy or chemotherapy are eligible (exception: previous treatment with the combination of CTLA-4 and PD-1 antibodies)
  • Patients must have recovered completely from any treatment-related acute toxicity associated with prior therapy
  • At least two weeks must have passed since the last systemic anti-cancer treatment
  • Patients with prior local therapy of brain metastases are eligible
  • Patients may have received irradiation therapies: A) None; B) Whole brain irradiation only, C) Stereotactic irradiation of single or few metastases, D) Combined B+C)
  • Screening laboratory values within 14 days prior to registration must meet the criteria: WBC ≥ 2,000/μL, Neutrophils ≥ 1,500/μL, Platelets ≥ 100 x103/μL, Hemoglobin > 9.0 g/dL, Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min, AST/ALT ≤ 3 x ULN, total bilirubin ≤ 1.5 x ULN (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL), INR ≤ 1.5
  • ECOG Performance Status 0, 1 or 2
  • Expected life expectancy of ≥ 3 months
  • Males and females ≥ 18 years old
  • Negative serum pregnancy test within 24 hours prior to the start of study drug for women of childbearing potential (WOCBP)
  • Women must not be breastfeeding
  • WOCBP must agree to follow instructions for method(s) of contraception, as indicated in the ICF, throughout the study and for 23 weeks after the last dose of investigational drug
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception, as indicated in the ICF, throughout the study and for a period of 31 weeks after the last dose of investigational drug. In addition, male patients must be willing to refrain from sperm donation during this time
  • Azoospermic males are exempt from contraceptive requirements. WOCBP who are permanently not heterosexually active are also exempt from contraceptive requirements, but must still undergo pregnancy testing as previously described.
  • Patients must agree to use at least two methods of contraception, with at least one highly effective method as listed in the ICF

Who cannot join

  • Diagnosed ocular melanoma
  • Previous systemic therapy with the combination of CTLA-4 and PD-1 antibodies
  • Use of any investigational or non-registered product within the 30 days before registration in the study
  • Prior active malignancy within the previous 3 years except locally curable cancers that have been apparently cured, such as: basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix, or breast
  • History of organ transplantation
  • Active infection requiring systemic therapy
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  • Active, known or suspected autoimmune disease (exceptions: patients with controlled Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment).
  • Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • Any serious or uncontrolled medical disorders thatmay increase the risk associated with study participation or study drug administration, impair the ability of the patient to receive protocol therapy, or interfere with the interpretation of study results in the opinion of the investigator
  • Known substance abuse or psychiatric disorders that would preclude cooperation with tany requirements of the trial
  • Legal incapacity or limited legal capacity
  • Administration of live, attenuated vaccine within 4 weeks prior to the start of study drug
  • Positive test for HBs Ag or HCV antibody
  • Known history of a positive test for HIV or known AIDS
  • Patients with known allergy or hypersensitivity to any of the study drugs or excipients
  • Patients with results of imaging or radiological examinations indicating increased cerebral pressure which would prevent lumbar puncture

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Germany11 sites

  • Elbe Kliniken Stade - Buxtehude GmbH

    Buxtehude

  • Universitätsklinik Carl Gustav Carus Dresden

    Dresden

  • HELIOS Klinikum Erfurt

    Erfurt

  • Universitätsklinikum Essen

    Essen

  • Universitätsklinikum Heidelberg

    Heidelberg

  • Gesellschaft für Klinische Forschung Ludwigshafen mbH

    Ludwigshafen

  • Universitätsklinikum Mannheim

    Mannheim

  • Klinikum rechts der Isar

    München

  • Harzklinikum Dorothea Christiane Erxleben GmbH

    Quedlinburg

  • Universitätsklinikum Regensburg

    Regensburg

  • Universitätsklinikum Tübingen

    Tübingen

Other trials in Germany

About this study

Official title: An Open Label Phase II Study to Evaluate Safety and Efficacy of Combined Treatment With Ipilimumab and Nivolumab in Patients With Four and More Symptomatic Brain Metastases of Melanoma

Up to 50% of patients with unresectable metastatic melanoma will develop brain metastases during their lifetime. A possible treatment options for patients with brain metastases are surgery and radiotherapy but usually for lesions in the range of < 3 brain metastases. This study was performed to evaluate the addition of immune checkpoint inhibitors in patients with stage IV melanoma with > 3 symptomatic brain metastases, who are not eligible for surgery or radiosurgery.

Read the detailed description

Brain metastases are a frequent problem in patients with melanoma. Up to 50% of patients with unresectable metastatic melanoma will develop brain metastases during their lifetime with a median overall survival of 4 months. Surgical removal or stereotactic radiosurgery of brain metastases can improve overall survival in patients with a limited number of lesions, usually in the range of one to three brain metastases depending on neuroanatomical localization. This benefit is no longer present when considering patients with > 3 brain metastases. As cytotoxic chemotherapy and multiple chemotherapeutic agents show only limited activity in > 3 brain metastases patients, immune checkpoint inhibitors such as ipilimumab and nivolumab offer new opportunities to improve disease outcomes for these patients.

This open label phase II study evaluates safety and efficacy of combined treatment with ipilimumab and nivolumab in patients with stage IV melanoma with four or more symptomatic brain metastases, who are not eligible for surgery or radiosurgery.

Being tested
Nivolumab, Ipilimumab
Medical subject headings
Melanoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabBiological

    Also called OPDIVO

    In the induction phase of this study nivolumab is administered as a IV infusion in combination with ipilimumab at a dose of 1 mg/kg for 4 cycles at three weeks interval and in a maintenance phase alone at a dose of 3 mg/kg every two weeks.

  • IpilimumabBiological

    Also called YERVOY

    In the induction phase of this study ipilimumab is administered as a IV infusion in combination with nivolumab at a dose of 3 mg/kg for 4 cycles at three weeks interval.

Study groups in NCT03728465
Study groupRoleWhat they receive
Treatment PhaseExperimentalTreatment phase is divided into the "Induction Phase" and "Maintenance Phase". During the induction phase patients are treated with 1 mg/kg nivolumab and 3 mg/kg ipilimumab, during the maintenance phase with nivolumab 3 mg/kg only .
Receives: Biological: Nivolumab; Biological: Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intracranial Control Rate after 6 months of treatment

    Proportion of patients with complete intracranial responses (CR), partial intracranial responses (PR) or stable intracranial disease (SD) after 6 months of treatment.

    Measured: 6 months

Secondary outcomes (8)

  1. Overall survival

    Number of patients who stay alive after 2 years.

    Measured: 2 years

  2. Progression-free survival

    Number of patients without progression after 2 years.

    Measured: 2 years

  3. Stereotactic irradiation or surgery of brain metastases after partial tumor remission

    Percentage of patients in whom stereotactic irradiation or surgery of all metastases becomes applicable after partial tumor remission.

    Measured: 2 years

  4. Tolerability according to NCI-CTCAE-Criteria

    All adverse events of all grades.

    Measured: 2 years

  5. Best Overall Response Rate with Complete Respone (CR)

    Percentage of patients with CR at six months of treatment.

    Measured: 6 months

  6. Best Overall Response Rate with Partial Response (PR)

    Percentage of patients with PR at six months of treatment.

    Measured: 6 months

  7. Cognitive function evaluation by standardized diagnostic procedures

    Systemic longitudinal neuropsychological evaluation to investigate the influence of therapy on cognitive performance will be performed by standardized diagnostic procedures.

    Measured: 2 years

  8. Quality of life evaluation with RAND 36-Item Health Survey 1.0

    Quality of life assessment is evaluated with the RAND 36-Item Health Survey questionnaires which include physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Evaluation will be performed according to the manual.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Nov 2018
  2. Study start10 Apr 2018
  3. Primary completion1 Jan 2021
  4. Study completion1 Jan 2021

Why it stopped: Lack of patients

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03728465
Sponsor's protocol ID
CA209-429
Status last verified
Oct 2018
First submitted
19 Oct 2018
Last updated
3 Feb 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Ipilimumab in people with Metastatic Melanoma and Brain Metastases, run by University Hospital Tuebingen at 11 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Lack of patients). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intracranial Control Rate after 6 months of treatment (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03728465.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2021.

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