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Malignant MelanomaPhase 1Mel-Ipi-RxNCT01557114

Study of Radiotherapy Administered in Combination With Ipilimumab in Patients With Unresectable Stage III or Stage IV Advanced Malignant Melanoma

A Phase 1 study testing Ipilimumab and Radiotherapy in people with Malignant Melanoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 2 sites in France.

Terminated

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

Official record
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Trial summary

RATIONALE:Anti-melanoma activity of Ipilimumab both as a single therapy and in association with melanoma peptides has been shown as well as synergy between radiation therapy and anti-CTLA-A mAb in several tumor animal models for both local tumor control and distant effects.Radiotherapy increases tumor immunogenicity… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma
What is being tested?
Ipilimumab and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
2 sitesFrance
Study dates
Mar 2011to Mar 2016
Phase
Phase 1
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

  • Willing and able to give written informed consent.
  • Histologic diagnosis of melanoma.
  • Unresectable locally advanced or metastatic melanoma with at least one melanoma metastasis accessible to radiation therapy.
  • Measurable disease according to immune related Response Criteria
  • Required values for initial laboratory tests:
  • WBC >= 2000/uL ANC >= 1000/uL Platelets >= 75 x 103/uL Hemoglobin >= 8 g/dL Creatinine <= 2,5 x ULN AST/ALT <= 2.5 x ULN for patients without liver metastasis or <= 5 x ULN for patients with liver metastasis Total Bilirubin <= 1,5.x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
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  • No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
  • ECOG Performance status of 0 or 1.
  • Men and women, >= 18 years of age.
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized.

Who cannot join

  • Suspected or known CNS tumors including brain metastasis.
  • Any other malignancy form which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
  • Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
  • Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
  • Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
  • A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA-4 inhibitor or agonist.
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  • Concomitant hormonal treatment, chemotherapy or immunotherapy.
  • Other investigational therapy.
  • Prior radiotherapy within the same body area.
  • Prior radiotherapy targeting fields containing flat bones.
  • Women of childbearing potential (WOCBP), defined above
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
  • Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 weeks after ipilimumab is stopped.

Trial locations and contacts

2 sites in 1 country.

France2 sites

  • Gustave Roussy Cancer Campus

    Villejuif, Val de Marne, 94805

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

Official title: A Dose Escalation Phase I Study of Radiotherapy Administered in Combination With Anti-CTLA4 Monoclonal Antibody (Ipilimumab) in Patients With Unresectable Stage III or Stage IV Advanced Malignant Melanoma

RATIONALE:Anti-melanoma activity of Ipilimumab both as a single therapy and in association with melanoma peptides has been shown as well as synergy between radiation therapy and anti-CTLA-A mAb in several tumor animal models for both local tumor control and distant effects.Radiotherapy increases tumor immunogenicity in several preclinical models by increasing MHC molecules expression and is able to induce significant tumor reduction in around 30% of cases. Thus, combining radiotherapy and administration of ipilimumab could elicit systemic antitumor response. Radiation therapy will expose tumor-associated antigens (TAA) and facilitate antigen presentation, and further blockade of CTLA-4 could amplify the immune antitumor response. In this therapeutical model, the use of the own patient tumor as a source of tumor antigens (in opposition with other vaccination protocols, where TAA are exogenic) is particularly adapted.

PURPOSE: This Phase I trial determines the side effects and best dose of radiation therapy administered in combination with ipilimumab.

Read the detailed description

OBJECTIVES:

Primary: To determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and recommended Phase 2 dose of radiation therapy administered in combination with ipilimumab.

Secondary:

Adverse event profiles Preliminary anti-tumor activity following escalating doses of radiation combined to ipilimumab using the immune related response criteria irRC overall survival in patients treated with this combination systemic immunologic anti tumor response intratumoral immune response pharmacodynamic effects of ipilimumab and radiotherapy in combination on Absolute Lymphocyte Count (ALC) associations between ALC and anti-tumor activity of ipilimumab and radiotherapy in combination

Being tested
Ipilimumab, Radiotherapy
Keywords
unresectable Stage III or stage IV advanced malignant melanoma
Medical subject headings
Melanoma

What participants receive

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

  • IpilimumabDrug

    Induction: Treatment with ipilimumab will be administered on weeks 1, 4, 7 and 10 at 10mg/kg.

    Maintenance: Ipilimumab will be administered intravenously over 90-minutes at 10 mg/kg every 12 weeks starting at week 24, for as long as the treating physician believes that there is a clinical benefit or for as long as patient is tolerant of therapy

  • RadiotherapyRadiation

    Radiation therapy 9 Grays in 3 Grays fractions Radiation therapy 15 Grays in 5 Grays fractions Radiation therapy 18 Grays in 6 Grays fractions Radiation therapy 24 Grays in 8 Grays fractions

Study groups in NCT01557114
Study groupRoleWhat they receive
radiation therapy with IpilimumabExperimentalNot described
Receives: Drug: Ipilimumab; Radiation: Radiotherapy

What is being measured

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

  1. Maximum Tolerated Dose of radiation therapy administered in combination with ipilimumab

    To determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) andrecommended Phase 2 dose of radiation therapy administered in combination with ipilimumab.

    Measured: between week 4 and week 10

Secondary outcomes (2)

  1. Adverse event profiles

    Adverse event profiles

    Measured: At an average of every four weeks during the treatment phase

  2. overall survival in patients treated with this combination

    overall survival in patients treated with this combination

    Measured: At an average of every four weeks during the treatment phase and then every three months during the follow-up phase

Timeline

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

  1. First posted19 Mar 2012 (estimated)
  2. Study startMar 2011
  3. Primary completionNov 2015
  4. Study completionMar 2016

Why it stopped: New compounds available in the indication (nivolumab/pembrolizumab), toxicity of ipilimumab

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01557114
Sponsor's protocol ID
CSET 2010/1663 -Mel-Ipi-Rx
Other IDs
2010-020317-93
Acronym
Mel-Ipi-Rx
Status last verified
Jun 2016
First submitted
16 Mar 2011
Last updated
9 Jun 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Boutros C, Chaput-Gras N, Lanoy E, Larive A, Mateus C, Routier E, Sun R, Tao YG, Massard C, Bahleda R, Schwob D, Ibrahim N, Khoury Abboud RM, Caramella C, Lancia A, Cassard L, Roy S, Soria JC, Robert C, Deutsch E. Dose escalation phase 1 study of radiotherapy in combination with anti-cytotoxic-T-lymphocyte-associated antigen 4 monoclonal antibody ipilimumab in patients with metastatic melanoma. J Immunother Cancer. 2020 Aug;8(2):e000627. doi: 10.1136/jitc-2020-000627.

    PubMed 32819972

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ipilimumab and Radiotherapy in people with Malignant Melanoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 2 sites in France.

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 10 inclusion and 13 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 9 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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: New compounds available in the indication (nivolumab/pembrolizumab), toxicity of ipilimumab). 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?

Maximum Tolerated Dose of radiation therapy administered in combination with ipilimumab (time frame: between week 4 and week 10). 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 NCT01557114, which also lists 1 linked publication.

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 9 Jun 2016.

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