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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

Phase 2
18 Years
Open (Enrolling)
Malignant Melanoma

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Trial Information

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

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

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Control rate

Outcome Description:

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

Outcome Time Frame:

at week 12

Safety Issue:


Principal Investigator

Benjamin Weide, Dr. med.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospital Tübingen


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

February 2012

Completion Date:

November 2014

Related Keywords:

  • Malignant Melanoma
  • Malignant melanoma
  • Melanoma