A Phase II Study to Evaluate Safety and Efficacy of Combined Treatment With Ipilimumab and Intratumoral Interleukin-2

July 17, 2015 updated by: Benjamin Weide, M.D., University Hospital Tuebingen

A Phase II Study to Evaluate Safety and Efficacy of Combined Treatment With Ipilimumab and Intratumoral Interleukin-2 in Pretreated Patients With Stage IV Melanoma

The current clinical trial shall clarify a synergistic effect with regards to efficiency by the combination of intratumoral injection of interleukin-2 (IL-2) and the intra-venous application of ipilimumab.

Study Overview

Status

Completed

Conditions

Detailed Description

Intratumoral injection of interleukin-2 (IL-2) into melanoma metastases is a highly efficient local treatment. Furthermore, a systemic effect is assumed based on the observation of a favorable long term outcome. However, objective responses in untreated lesions have not been observed yet. Ipilimumab seems to be efficient in a subset of treated patients by inhibition of down-regulation of tumor-specific cellular immune-responses. In the context of the proposed trial, we assume (i) that ipilimumab could potentiate systemic melanoma-specific immune responses, which are primarily induced by intratumoral IL-2 and (ii) that these immune responses become more effective with regards to not IL-2 injected distant lesions. Therefore we assume a synergistic effect with regards to efficiency by the combination.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Tübingen, Germany, 72076
        • University Hospital Tübingen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Willing and able to give written informed consent;
  • Histological diagnosis of malignant melanoma;
  • Stage IV melanoma;
  • At least one injectable lesions > 5 mm (longest diameter) or at least 5 injectable lesions < 5 mm.
  • Measurable disease. Note: lesions, which are designated for direct IL -2 injections, must not be considered in the evaluation of measurability;
  • Men and women, at least 18 years of age;
  • Patient must have demonstrated 1 of the following in response to at least 1 cycle of 1 or more systemic regimens:

    1. relapse following an objective response (PR/CR);
    2. failed to demonstrate an objective response (PR/CR); or
    3. inability to tolerate treatment due to unacceptable toxicity
  • At least 4 weeks since treatment (chemotherapy, biochemotherapy, surgery, radiation, immunotherapy, etc.) for melanoma and recovered from any clinically significant toxicity experienced during treatment;
  • Life expectancy ≥3 months;
  • ECOG performance status of 0 or 1;
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab;
  • No known active or chronic infection with HIV, Hepatitis B, or Hepatitis C
  • Required values for initial laboratory tests:
  • Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study and for up to 26 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized

Exclusion Criteria:

  • Any other prior malignancy from 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;
  • Ocular melanoma; mucosal melanoma
  • Either untreated or symptomatic central nervous system (CNS) metastases (patients with brain metastases who are identified at screening may be rescreened after the lesion(s) have been appropriately treated);
  • Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic autoimmune 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). Patients with vitiligo may be included.
  • 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 systemic treatment with ipilimumab, CD137 agonist, CTLA 4 inhibitor, CTLA-4 agonist or IL-2 in stage IV melanoma.
  • Concomitant or less than 4 weeks off therapy with any of the following: interferon; other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; chronic use of systemic corticosteroids.
  • Women of childbearing potential (WOCBP), defined in Section 5.3, who:

    1. are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or
    2. have a positive pregnancy test at baseline, or
    3. are pregnant or breastfeeding.
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious) illness.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ipilimumab
Ipilimumab i.v. + Interleukin-2 intratumoral
intratumoral injections of 9 MIU/day on days 1, 4, 8, 11, 15, 18, 22 and 25. The administered dose will be distributed between all injectable soft-tissue metastases
Other Names:
  • Proleukin®
IV infusion, 3 mg/kg, day 2, 23, 44, 65
Other Names:
  • Proleukin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Control rate
Time Frame: at week 12
To determine efficacy of the combined treatment with ipilimumab and intratumoral IL-2 by assessment of Disease control rate according to immune-related response criteria (irDCR) at week 12
at week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tolerability
Time Frame: within 12 months after start of treatment
Tolerability according to NCI-CTCAE-Criteria (version 4)
within 12 months after start of treatment
Overall survival
Time Frame: within 12 months after start of treatment
Overall survival
within 12 months after start of treatment
Best Overall Response Rate
Time Frame: within 12 months after start of treatment
Best Overall Response Rate (irBORR) according to irRC
within 12 months after start of treatment
Overall response rate
Time Frame: at week 12
Overall response rate (sum of irPR and irCR) according to irRC
at week 12
Overall Response Rate
Time Frame: at week 12
Overall Response Rate according to modified mWHO criteria
at week 12
Best Overall Response Rate
Time Frame: within 12 months after start of treatment
Best Overall Response Rate according to modified mWHO criteria
within 12 months after start of treatment
Response rate of injected metastases only
Time Frame: at week 12
Response rate of injected metastases only
at week 12
Rate of patients with substantial increase of anti-melanoma T-cells in peripheral blood during treatment
Time Frame: within 22 weeks after start of treatment
Rate of patients with substantial increase of anti-melanoma T-cells in peripheral blood during treatment
within 22 weeks after start of treatment
Changes in T-cell subsets during treatment
Time Frame: within 22 weeks after start of treatment
Changes in T-cell subsets during treatment
within 22 weeks after start of treatment
Changes in subsets of tumor-infiltrating lymphocytes during treatment
Time Frame: within 22 weeks after start of treatment
Changes in subsets of tumor-infiltrating lymphocytes during treatment
within 22 weeks after start of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Benjamin Weide, Dr. med., University Hospital Tübingen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (ACTUAL)

September 1, 2014

Study Completion (ACTUAL)

June 1, 2015

Study Registration Dates

First Submitted

November 23, 2011

First Submitted That Met QC Criteria

November 25, 2011

First Posted (ESTIMATE)

November 28, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

July 21, 2015

Last Update Submitted That Met QC Criteria

July 17, 2015

Last Verified

July 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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