Radiotherapy As an Immunological Booster in Patients with Metastatic Melanoma or Renal Cell Carcinoma Treated with High-dose Interleukin-2

NCT01884961 | Completed Phase 2

• 2 other identifiers: IRST172.032012-001786-32
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Metastatic Renal Cell Cancer; Malignant Melanoma, Metastatic

Outcome Measures

Primary Outcomes (2)

• immunological efficacy

  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

  3 years

• Biomarkers predictive value for treatment benefit

  Determination of the predictive value of pretreatment biomarkers in identifying patients who will benefit from combined RT/HDIL-2 treatment

  3 years

Secondary Outcomes (3)

• Toxicity from the time of their first treatment with HD 2.

  3 years

• Response Rate

  3 years

• Overall Survival

  3 years

Study Arms (1)

arm A

EXPERIMENTAL

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

Interventions

Boost of radiotherapy + high dose IL-2 treatment OTHER

Boost of radiotherapy + high dose IL-2 treatment

arm A

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed non resectable stage III or IV advanced melanoma or Renal Cell Carcinoma (RCC).
• 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).
• At least one tumor lesion accessible for bioptic sampling.
• 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);
• Male or Female, aged \>= 18 years.
• Life expectancy of greater than 3 months.
• ECOG performance status \<=1
• 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

You may not qualify if:

• Patient with stage I or II melanoma or RCC
• 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.
• Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
• 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.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2 or other agents used in the study.
• Any autoimmune disease which could be exacerbated by IL-2
• A medical illness requiring chronic treatments with corticosteroids or other immunosuppressive agents
• A history of significant cardiovascular disease, including myocardial infarction, congestive heart failure, primary cardiac arrhythmias, angina pectoris or cerebrovascular accident
• 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.
• 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);
• HIV-positivity, whether or not symptomatic.

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead

Study Sites (1)

UO Oncologia Medica, IRCCS IRST

Meldola (FC), FC, 47014, Italy

Location

Related Publications (1)

• Ridolfi L, de Rosa F, Ridolfi R, Gentili G, Valmorri L, Scarpi E, Parisi E, Romeo A, Guidoboni M. 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. J Transl Med. 2014 Sep 23;12:262. doi: 10.1186/s12967-014-0262-6.

  PMID: 25245327 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Melanoma; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Laura Ridolfi, MD

  IRST IRCCS, Meldola

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2013
• First Posted: June 24, 2013
• Study Start: July 9, 2012
• Primary Completion: June 1, 2021
• Study Completion: January 1, 2025
• Last Updated: January 13, 2025

Record last verified: 2025-01

Locations

IT (1)