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Radiotherapy as an Immunological Booster in Patients With Metastatic Melanoma or Renal Cell Carcinoma Treated With High-dose Interleukin-2 (IL2HD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Information provided by (Responsible Party):
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori Identifier:
First received: June 19, 2013
Last updated: September 28, 2016
Last verified: September 2016

Title: Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with High-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response

Phase: Proof of Principle phase II study

Study Design: Single center, open-label trial to assess the immune response and potential biomarkers predictive of response

Study Duration:

Total duration: 36 months Enrollment: 20 months Treatment: 5 months per patient Follow-up every three months

Number of Subjects:

Mini-max two-stage Simon design:

• Step 1: 7 patients enrolled

If tumor antigen-specific immune response is observed in at least 3 patients:

• Step 2: recruitment of an additional 12 patients

Condition Intervention Phase
Metastatic Renal Cell Cancer
Malignant Melanoma, Metastatic
Other: Boost of radiotherapy + high dose IL-2 treatment
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Radiotherapy as an Immunological Booster in Patients With Metastatic Melanoma or Renal Cell Carcinoma Treated With High-dose Interleukin-2: Evaluation of Biomarkers of Immunologic and Therapeutic Response

Resource links provided by NLM:

Further study details as provided by Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori:

Primary Outcome Measures:
  • immunological efficacy [ Time Frame: 3 years ]
    Determination of the immunological efficacy of the combined RT (radiotherapy)/HDIL-2 (high dose Interleukin 2) treatment in terms of ability of the treatment to enhance the proportion of circulating immune effectors specific for tumor antigens known to be expressed in RCC (Renal Cell Carcinoma) and/or melanoma

  • Biomarkers predictive value for treatment benefit [ Time Frame: 3 years ]
    Determination of the predictive value of pretreatment biomarkers in identifying patients who will benefit from combined RT/HDIL-2 treatment

Secondary Outcome Measures:
  • Toxicity [ Time Frame: 3 years ]
    Evaluation of safety and tollerability of the experimental treatment

  • Response Rate [ Time Frame: 3 years ]
    Evaluation of the response rate of treated patients

  • Overall Survival [ Time Frame: 3 years ]
    Evaluation of the overall survival of treated patients

Estimated Enrollment: 19
Study Start Date: June 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: arm A

Boost of radiotherapy + high dose IL-2 treatment: Three daily doses boost radiotherapy at 6-12 Gy to at least 1, and up to a maximum of 5, metastatic fields, will be administrated on days -4 -3 -2 or -3 -2 -1 before the first and the third cycle of IL-2 (Interleukin 2). The first day of administration of IL-2 of each cycle is the day +1.

Treatment with IL-2 (dose 18 MIU/m2/day in 500cc by continuous IV (intravenous) infusion for 72 hours) will start on day +1 and will be administered every 3 weeks up to 4 cycles, than every 3-4 weeks for a further 2 cycles.

Patients will be evaluated every 8 weeks with computed tomography to determine the response, and every 3 months after completion of treatment until death.

Other: Boost of radiotherapy + high dose IL-2 treatment
Boost of radiotherapy + high dose IL-2 treatment

  Show Detailed Description


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must have histologically or cytologically confirmed non resectable stage III or IV advanced melanoma or Renal Cell Carcinoma (RCC).
  2. Patients must have a minimum of two lesions and one of which must be measurable, (it can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan).
  3. At least one tumor lesion accessible for bioptic sampling.
  4. Prior lines (maximum 4) of chemotherapy, immunotherapy or biological therapy (e.g. inhibitors of B-Raf or c-Kit, Ipilimumab, etc.) for advanced disease are allowed (patients must have finished prior treatments at least 4 weeks before the first IL2 dose);
  5. Male or Female, aged >= 18 years.
  6. Life expectancy of greater than 3 months.
  7. ECOG performance status <=1
  8. Patients must have normal organ and marrow function as defined below:

    • leukocytes >=3,500/microL
    • absolute neutrophil count >=1,500/microL
    • platelets >= 100,000/microL
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of normal
    • creatinine < 1,2 mg/dl
    • haemoglobin > 9.0 gm/dl
    • ECG and echocardiogram within normal institutional limits
    • Pulmonary function tests within normal institutional limits (to be performed only in patients with lung metastases or history of impaired lung function)
  9. no contraindication for the use of vasopressor agents
  10. Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
  11. Participant is willing and able to give informed consent for participation in the study.

Exclusion Criteria:

  1. Patient with stage I or II melanoma or RCC
  2. Patients who have had chemotherapy or radiotherapy or immunotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  3. Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
  4. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  5. History of allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2 or other agents used in the study.
  6. Any autoimmune disease which could be exacerbated by IL-2
  7. A medical illness requiring chronic treatments with corticosteroids or other immunosuppressive agents
  8. A history of significant cardiovascular disease, including myocardial infarction, congestive heart failure, primary cardiac arrhythmias, angina pectoris or cerebrovascular accident
  9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  10. Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix);
  11. HIV-positivity, whether or not symptomatic.
  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 identifier: NCT01884961

Contact: Oriana Nanni, PhD +390543739266

UO Oncologia Medica, IRCCS IRST Recruiting
Meldola (FC), FC, Italy, 47014
Contact: Laura Ridolfi, MD         
Principal Investigator: Laura Ridolfi, MD         
Sponsors and Collaborators
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Principal Investigator: Laura Ridolfi, MD IRST IRCCS, Meldola
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori Identifier: NCT01884961     History of Changes
Other Study ID Numbers: IRST172.03
2012-001786-32 ( EudraCT Number )
Study First Received: June 19, 2013
Last Updated: September 28, 2016

Additional relevant MeSH terms:
Nevi and Melanomas
Carcinoma, Renal Cell
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Glandular and Epithelial
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs processed this record on March 29, 2017