Vaccination With Dendritic Cells Pulsed With Autologous Tumor Homogenate in Combination With HD-IL2 and Immunomodulating Radiotherapy in Metastatic RCC

NCT03226236 | Withdrawn Phase 2

• 2 other identifiers: IRST189.032015-000556-14
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Single center, open-label Proof of Principle phase II trial to assess objective response (ORR). 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 vaccine+IL-2. The first day of administration of vaccine is day +1 and of IL-2 is day +2. Treatment vaccine plus IL-2 (dose 18 MIU/m2/day in 500cc by continuous IV infusion for 72 hours) will be administered every 3 weeks up to 6 cycles. Total duration of the trial: 36 months

• Enrolment period: 24 months
• Treatment: maximum of 6 cycles (5 months) per patient
• Follow-up every three months until patient died (follow-up until PD and only survival contacts and subsequent therapy for metastatic disease after PD).

Conditions

Carcinoma, Renal Cell; Vaccination; Secondary

Keywords

Carcinoma, Renal Cell; vaccination; dendritic cells; autologous tumor homogenate; High Dose -IL2; immunomodulating radiotherapy; secondary

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) by Immune related Response Criteria( irRC)

  The analysis will be performed on an intention to treat population, i.e. all patients having received at least 2 cycles of therapy.

  up to 24 months

Secondary Outcomes (5)

• Overall survival (OS)

  up to 24 months

• Duration of response

  up to 24 months

• Progression free survival

  up to 24 months

• Immunologic efficacy

  up to 24 months

• Adverse events evaluation

  up to 24 months

Study Arms (1)

study treatment

EXPERIMENTAL

boost radiotherapy (XRT) plus intradermal autologous dendritic cell vaccine loaded with autologous tumor homogenate (Autologous DC vaccine) plus High-Dose IL-2

Radiation: boost radiotherapy (XRT); Biological: Autologous DC vaccine; Drug: High-Dose IL-2

Interventions

boost radiotherapy (XRT) RADIATION

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 vaccine+IL-2

study treatment

Autologous DC vaccine BIOLOGICAL

The first dose (7 to 14 x 10\_6 total dendritic cells) will be performed with freshly prepared vaccine, 9 days after leukapheresis; on day +1 starting from cycle 2 (3 weeks after the first cycle, on completion of QA assessments on the cryopreserved products), 5 additional doses will be administered every 3 weeks until maximum six vaccines.

study treatment

High-Dose IL-2 DRUG

high dose IL-2: 18 MIU/m2/day in 500cc administered by continuous IV infusion for 72 hours starting day +2.

study treatment

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Written Informed Consent: patients must be willing and able to give written informed consent, that have to be given before starting of screening procedure.
• Availability of autologous tumor tissue fulfilling acceptance criteria prescribed by the "Product Specification File".
• Patients must have histologically or cytologically confirmed RCC (all histology types except for urothelial cancer);
• Patients must have stage IV disease in progression after at least 1 TKI and/or antiangiogenetic and/or mTOR inhibitors therapy (patients must have finished prior treatments at least 4 weeks before the first IL2 dose)
• Patients must have at least one measurable lesion, according to the irRC response criteria (see section 8 ), after asportation of tumor tissue for vaccine preparation. The tumor lesions that will be irradiated are excluded for response evaluation.
• Life expectancy of greater than 3 months.
• ECOG performance status 0-1
• Patients must have organ and marrow function as defined below:
• leukocytes \>4000/µL
• absolute neutrophil count \>1,500/µL
• platelets \>100,000/µL
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal
• creatinine \< 1.5 mg/dl
• haemoglobin \>8.0 gm/dl

You may not qualify if:

• Patients who have positive tests to HCV, HBV, HIV, or syphilis (specific blood testing must be performed within 30 days before any GMP-regulated activity (leukapheresis and collection of tumor biopsies to be used for tumor homogenate preparation).
• Patients who did not have prior lines of systemic therapy for advanced disease.
• Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
• 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 (on physician's judgment).
• Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 3 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix);
• 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.
• 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
• HIV-positivity, whether or not symptomatic
• Any contraindication to undergo leukapheresis as evaluated by transfusionist (e.g. severe anemia, piastrinopenia, oral anticoagulant therapy) or to undergo surgery.

Sponsors & Collaborators

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

Study Sites (1)

UO Immunoterapia e Laboratorio TCS, IRCCS IRST

Meldola (FC), FC, 47014, Italy

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

Interleukin-2

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Laura Ridolfi, MD

  UO Immunoterapia e Laboratorio TCS, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) S.r.l IRCCS

  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: September 28, 2016
• First Posted: July 21, 2017
• Study Start: March 1, 2016
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: November 13, 2018

Record last verified: 2018-11

Locations

IT (1)