Metastatic Renal Cell CancerPhase 2IL2HDNCT01884961

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

A Phase 2 study testing Boost of radiotherapy + high dose IL-2 treatment in people with Metastatic Renal Cell Cancer and Malignant Melanoma, Metastatic, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Metastatic Renal Cell Cancer, Malignant Melanoma, Metastatic
What is being tested?: Boost of radiotherapy + high dose IL-2 treatment
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 46 participants
Where: 1 siteItaly
Study dates: 9 Jul 2012to Jan 2025
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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
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)
no contraindication for the use of vasopressor agents
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
Participant is willing and able to give informed consent for participation in the study.

Who cannot join

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

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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.

Trial locations and contacts

1 site in 1 country.

Italy1 site

UO Oncologia Medica, IRCCS IRST
Meldola (FC), FC, 47014

Other trials in Italy

About this study

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

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

Read the detailed description

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

Primary objectives:

to determine the tumor antigen-specific immune response induced by the treatment
to prospectively determine the predictive/prognostic value of pretreatment biological features in identifying patients who will benefit from HDIL-2-based therapy

Secondary end points:

Toxicity
Response Rate
Overall Survival.

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

Study Product, Dose, Route, Regimen and duration of administration:

Three daily doses boost radiotherapy (XRT) 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. 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 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.

IL-2 will be withheld for refractory hypotension (hypotension where isotropic or vasoactive therapy is ineffective and that persists despite specific medical therapy set), anuria for > 24 hours, respiratory distress, confusion, sustained ventricular tachycardia, signs of myocardial ischemia or myocarditis, persistant metabolic acidosis, atrial fibrillation and documented systemic infection.

Patients will be evaluated every 8 weeks with computed tomography to determine the response, and every 3 months after completion of treatment until death (the time of disease progression and the initiation of alternative therapies will also be documented).

Statistical Methodology:

A minimax two-stage Simon design will be employed. A 40% immune response will preclude further study, whereas a 70% response rate will indicate that further study would be warranted. Using alfa and beta errors of 0.10, 7 patients will be enrolled during the first stage, and if an immune response is observed in at least 3 patients the study will go on, and an additional 12 patients will be treated. The treatments will be considered active if a tumor antigen-specific immune response is observed in 11 out of 19 patients treated. The analysis will be performed on an intention to treat population, i.e. all patients having received at least one cycle of therapy.

Conditions: Metastatic Renal Cell Cancer, Malignant Melanoma, Metastatic
Being tested: Boost of radiotherapy + high dose IL-2 treatment
Medical subject headings: Carcinoma, Renal Cell, Melanoma, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Boost of radiotherapy + high dose IL-2 treatmentOther
Boost of radiotherapy + high dose IL-2 treatment

Study groups in NCT01884961
Study group	Role	What they receive
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. Receives: Other: Boost of radiotherapy + high dose IL-2 treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 3 years

Secondary outcomes (3)

Toxicity from the time of their first treatment with HD 2.
Evaluation of safety and tollerability of the experimental treatment. The percentage of patients reporting an Adverse Event (AE) up to 30 days after HD-IL-2 treatment will be tabulated with 95% confidence intervals, by type of AE. The overall rate of grade 3-4 related AE will be computed.
Measured: 3 years
Response Rate
Evaluation of the response rate of treated patients
Measured: 3 years
Overall Survival
Evaluation of the overall survival of treated patients
Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Jul 2012Jan 2025

First posted24 Jun 2013 (estimated)
Study start9 Jul 2012
Primary completionJun 2021
Study completionJan 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Metastatic Renal Cell CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01884961
Sponsor's protocol ID: IRST172.03
Other IDs: 2012-001786-32
Acronym: IL2HD
Status last verified: Jan 2025
First submitted: 19 Jun 2013
Last updated: 13 Jan 2025
Results posted: No
Data monitoring committee: No

Publications

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.
PubMed 25245327

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01884961
Acronym / sponsor ID: IL2HD / IRST172.03
Conditions: Metastatic Renal Cell Cancer, Malignant Melanoma, Metastatic
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSUniversity, hospital or other
Study start: 9 Jul 2012 (actual)
Primary completion: Jun 2021 (actual)
Study completion: Jan 2025 (actual)
First posted: 24 Jun 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

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

Primary objectives:

to determine the tumor antigen-specific immune response induced by the treatment
to prospectively determine the predictive/prognostic value of pretreatment biological features in identifying patients who will benefit from HDIL-2-based therapy

Secondary end points:

Toxicity
Response Rate
Overall Survival.

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

Study Product, Dose, Route, Regimen and duration of administration:

Statistical Methodology:

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
arm A	Experimental	Other: Boost of radiotherapy + high dose IL-2 treatmentBoost 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (20 listed)

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.

Key exclusion criteria (11 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Boost of radiotherapy + high dose IL-2 treatmentBoost of radiotherapy + high dose IL-2 treatment	Other	arm A

Primary outcome

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

3 secondary outcomes

Toxicity from the time of their first treatment with HD 2.
Time frame: 3 years
Response Rate
Time frame: 3 years
Overall Survival
Time frame: 3 years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
Derived from this study: PubMed 25245327Ridolfi 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.

Related trials for Metastatic Renal Cell Cancer

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1/2
Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer
Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer
RecruitingPhase 2
Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
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Active, not recruitingPhase 1
P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors
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RecruitingPhase 1
Open-Label Phase 1/2 Study of NEO-811 in Subjects With Locally Advanced or Metastatic Non-Resectable Clear Cell Renal Cell Carcinoma
Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Laura Ridolfi, MD principal investigator

IRST IRCCS, Meldola

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

immunological efficacy (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01884961, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2025.