Uptake and Biodistribution of 89Zirconium-labeled Ipilimumab in Ipilimumab Treated Patients With Metastatic Melanoma

NCT03313323 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: 2015.300
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Ipilimumab, a monoclonal antibody targeting CTLA-4, is approved for the treatment of metastatic melanoma and significantly increases median overall survival. However, use of this drug is associated with immune related adverse events (IRAEs) like colitis, hepatitis, dermatitis, alveolitis and hypophysitis in 10-40% of the patients. In general IRAEs are manageable by cessation of ipilimumab in combination with treatment with corticosteroids or TNF-alpha blockade but they can be severe or even life-threatening. In addition, treatment with ipilimumab is expensive. Because of the high costs and the potential serious toxicity of ipilimumab, it is of great importance to identify biomarkers that correlate with clinical activity and can be used to select patients that will benefit from CTLA-4 blockade therapy. The investigators hypothesize that differences in response to treatment with ipilimumab are due to variability in the pharmacodynamics and -kinetics of the antibody. It is hypothesized that patients who do not respond to treatment with ipilimumab have lower drug levels in tumor tissues as compared to patients with a good response to therapy. In addition, the investigators hypothesize that IRAEs are associated with high drug levels in the affected tissue. To visualize molecular interactions a novel technique is used in which positron emission tomography (PET) is combined with labeled monoclonal antibodies. Because ipilimumab induces activation of T-lymphocytes it is hypothesized that uptake of 89Zr-ipilimumab in tumor lesions and normal tissue is different (i.e. higher) after the second administration of ipilimumab (3 weeks after first injection). Therefore immuno-PET scans will be performed after the first and after the second injection of ipilimumab. Objective: Part one: The primary objective is: 1\. To assess uptake (visual and quantitative) of 89Zr-ipilimumab in tumor lesions and biodistribution at two timepoints (at start of ipilimumab therapy and after the second injection 3 weeks later). The secondary objectives are:

1. 1.To determine the correlation between tumor targeting of ipilimumab and response to therapy.
2. 2.To assess uptake (visual and quantitative) of 89Zr-ipilimumab in normal tissues.
3. 3.To determine de correlation between organ targeting and toxicity

Conditions

Melanoma

Keywords

Immuno-PET; Ipilimumab; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• The detection of 89Zr-ipilimumab in tumor lesions

  The detection (visual and quantitative) of 89Zr-ipilimumab in tumor lesions (the short axis diameter of a measurable tumor lesion is ≥1 cm. The five largest lesions will be used for evaluation).

  3 weeks

Secondary Outcomes (9)

• The visual detection of 89Zr-ipilimumab in normal tissue

  3 weeks

• The quantitative detection of 89Zr-ipilimumab in normal tissue

  3 weeks

• Comparison between uptake of 89Zr-ipilimumab

  3 weeks

• Clinical outcome (response)

  Every 12 weeks, from date of starting therapy until the date of first documented progression or date of death from any cause, whichever came first. Assessed through study completion, an average of 1 year

• Clinical outcome (survival)

  Through study completion, an average of 1 year

Study Arms (1)

Zirconium-ipilimumab

EXPERIMENTAL

Zirconium-ipilimumab is an experimental tracer and is administered at start of ipilimumab treatment and after second infusion 3 weeks later

Biological: 89Zirconium-labeled ipilimumab

Interventions

89Zirconium-labeled ipilimumab BIOLOGICAL

Metastatic melanoma patients, who are treated with ipilimumab (3 mg/kg), will be infused with 89Zr-labeled ipilimumab within 2 hours after injection of the first and second standard ipilimumab doses. Peripheral blood mononuclear cells (PBMCs) will be collected for immunomonitoring.

Zirconium-ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced/metastatic melanoma.
• Scheduled for treatment with ipilimumab.
• Age ≥ 18 years.
• Histological or cytological documentation of cancer is required.
• WHO Performance Status of 0 or 1.
• At least 1 measurable lesion.
• Signed informed consent must be obtained prior to any study procedures.
• Patients must be able to adhere to the study appointments and other protocol requirements.

You may not qualify if:

• Previous exposure to ipilimumab.
• Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start treatment. Both men and women enrolled in this trial must agree to use adequate barrier birth control measures (e.g. cervical cap, condom and diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between study drug and oral contraceptives. Concomitant use of oral and barrier contraceptives is advised. Contraception is necessary for at least 6 months after receiving study drug.
• Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy during the study or within 4 weeks after starting the study drug.
• Radiotherapy of target lesions during study or within 4 weeks after starting the study drug. Palliative radiotherapy will be allowed.
• Major surgery within 28 days of start of study drug.
• Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
• Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

VU Medical Center

Amsterdam, North Holland, 1181HV, Netherlands

RECRUITING

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Alfonsus JM van den Eertwegh, Prof.dr.

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jelle Arts

CONTACT

+31 (0)20 4444254; trialoffice-onc@vumc.nl

Alfonsus JM van den Eertwegh, Prof.dr.

CONTACT

+31 (0)20 4444321; vandeneertwegh@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: October 18, 2017
• Study Start: February 16, 2017
• Primary Completion: February 15, 2022
• Study Completion: February 15, 2022
• Last Updated: April 15, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)