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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by University Hospital Tuebingen
Sponsor:
Information provided by (Responsible Party):
Benjamin Weide, M.D., University Hospital Tuebingen
ClinicalTrials.gov Identifier:
NCT01480323
First received: November 23, 2011
Last updated: October 2, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Malignant Melanoma
Drug: Interleukin-2
Drug: Ipilimumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University Hospital Tuebingen:

Primary Outcome Measures:
  • Control rate [ Time Frame: at week 12 ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Tolerability [ Time Frame: within 12 months after start of treatment ] [ Designated as safety issue: Yes ]
    Tolerability according to NCI-CTCAE-Criteria (version 4)

  • Overall survival [ Time Frame: within 12 months after start of treatment ] [ Designated as safety issue: Yes ]
    Overall survival

  • Best Overall Response Rate [ Time Frame: within 12 months after start of treatment ] [ Designated as safety issue: No ]
    Best Overall Response Rate (irBORR) according to irRC

  • Overall response rate [ Time Frame: at week 12 ] [ Designated as safety issue: No ]
    Overall response rate (sum of irPR and irCR) according to irRC

  • Overall Response Rate [ Time Frame: at week 12 ] [ Designated as safety issue: No ]
    Overall Response Rate according to modified mWHO criteria

  • Best Overall Response Rate [ Time Frame: within 12 months after start of treatment ] [ Designated as safety issue: No ]
    Best Overall Response Rate according to modified mWHO criteria

  • Response rate of injected metastases only [ Time Frame: at week 12 ] [ Designated as safety issue: No ]
    Response rate of injected metastases only

  • 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 ] [ Designated as safety issue: No ]
    Rate of patients with substantial increase of anti-melanoma T-cells in peripheral blood during treatment

  • Changes in T-cell subsets during treatment [ Time Frame: within 22 weeks after start of treatment ] [ Designated as safety issue: No ]
    Changes in T-cell subsets during treatment

  • Changes in subsets of tumor-infiltrating lymphocytes during treatment [ Time Frame: within 22 weeks after start of treatment ] [ Designated as safety issue: No ]
    Changes in subsets of tumor-infiltrating lymphocytes during treatment


Estimated Enrollment: 41
Study Start Date: February 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Interleukin-2
    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 Name: Proleukin®
    Drug: Ipilimumab
    IV infusion, 3 mg/kg, day 2, 23, 44, 65
    Other Name: Proleukin
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01480323

Contacts
Contact: Benjamin Weide, Dr. med. +49 7071 29 ext 85748 Benjamin.weide@med.uni-tuebingen.de

Locations
Germany
University Hospital Tübingen Recruiting
Tübingen, Germany, 72076
Contact: Benjamin Weide, Dr. med.    +49 7071 29 ext 85748    Benjamin.weide@med.uni-tuebingen.de   
Principal Investigator: Benjamin Weide, Dr. med.         
Sponsors and Collaborators
University Hospital Tuebingen
Investigators
Principal Investigator: Benjamin Weide, Dr. med. University Hospital Tübingen
  More Information

No publications provided

Responsible Party: Benjamin Weide, M.D., Dr. Benjamin Weide, University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT01480323     History of Changes
Other Study ID Numbers: 5027000
Study First Received: November 23, 2011
Last Updated: October 2, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Tuebingen:
Malignant melanoma

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Interleukin-2
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 30, 2014