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AxIn Study - Phase II Study of Axitinib Intensification Plus Nivolumab Compared to Nivolumab Alone After Induction With Nivolumab Plus Ipilimumab in mRCC Patients Without Previous Complete Response.

Studio Clinico

Patologia: Tumori del rene

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: 

Fase di studio: II

Richiesta mandatoria di tessuto: 

Linee di trattamento: Mantenimento

Criteri di inclusione: 

1. Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype and candidate to receive nivolumab after nivolumab plus ipilimumab induction as per standard clinical practice.
2. Completion of the induction of nivolumab and ipilimumab without toxicity ≥ G2 and no complete response or progressive disease.
3. Male or female subjects aged ≥ 18 years
4. Available tumor tissue sample.
5. At least one measurable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
6. Eastern Cooperative Oncology Group performance status 0 or 1.
7. Adequate organ and bone marrow function based upon meeting all of the following laboratory criteria within 10 days before the start of treatment:
   - Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L)
   - Platelets ≥ 100,000/mm3 (≥ 100 GI/L).
   - Haemoglobin ≥ 9 g/dL (≥ 90 g/L).
   - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × upper limit of normal.
   - Total bilirubin ≤ 1.5 × the upper limit of normal. For subjects with Gilbert's disease ≤ 3 mg/dL (≤ 51.3 µmol/L).
   - Serum creatinine ≤ 2.0 × upper limit of normal or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockroft-Gault.
8. Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
9. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of study treatment.
10. Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrhoeic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antioestrogens, low body weight, ovarian suppression or other reasons.

Criteri di esclusione: 

1. Prior treatment with systemic therapy for advanced RCC with the exclusion of the induction of nivolumab and ipilimumab.
2. Prior adjuvant or neoadjuvant therapy
3. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis
4. Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of the start of treatment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix or low-grade prostate cancer with no plans for treatment intervention.
5. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the start of treatment. Systemic treatment with radionuclides within 6 weeks before the start of treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before the start of treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of treatment.
7. Concomitant anticoagulation at therapeutic doses with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel).
8. In past 6 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack.
9. Chronic treatment with corticosteroids or other immunosuppressive agents (with the exception of inhaled or topical corticosteroids or corticosteroids with a daily dosage equivalent ≤ 10 mg prednisone if given for disorders other than renal cell cancer). Subjects with brain metastases requiring systemic corticosteroid are not eligible.
10. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
   I. Cardiovascular disorders:
        - Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias.
        - Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.
        - Stroke (including TIA), myocardial infarction, or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before the start of treatment.
    II. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
        - Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction.
        - Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before the start of treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before the start of treatment.
    III. Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 3 months before the start of treatment.
    IV. Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
    V. Lesions invading major pulmonary blood vessels.
    VI. Other clinically significant disorders such as:
        - Active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)- related illness, or chronic hepatitis B or C infection.
        - Serious non-healing wound/ulcer/bone fracture.
        - Malabsorption syndrome.
        - Uncompensated/symptomatic hypothyroidism.
        - Moderate to severe hepatic impairment (Child-Pugh B or C).
        - Requirement for hemodialysis or peritoneal dialysis.
        - History of solid organ transplantation.
        - In past 6 months: deep vein thrombosis or pulmonary embolism.
        - History of aneurysms and/or artery dissections
11. Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 3 months before the start of treatment. 12. Complete wound healing from major surgery must have occurred 1 month before the start of treatment and from minor surgery (e.g., simple excision, tooth extraction) at least 10 days before the start of treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
12. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 msec within 1 month before the start of treatment (see Section 5.5.4 for Fridericia formula). Three ECGs must be performed. If the average of these three consecutive results for QTcF is ≤ 500 msec, the subject meets eligibility in this regard.
13. Vaccination within 4 weeks of the first dose of nivolumab and while on trials is prohibited except for administration of inactivated vaccines.
14. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
15. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
16. Has a history of substance abuse or medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
17. Has illness or medical conditions that are unstable or could jeopardize the safety of the patient and his or her compliance in the study.
18. Pregnant or lactating females.
19. Inability to swallow tablets or capsules.
20. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
21. Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Trattamento sperimentale: 

ARM A: Axitinib (starting dose 5 mg BID orally) in addition to nivolumab (lat dose of 480 mg IV every four weeks as per standard clinical practice).

Trattamento di controllo: 

ARM B: Nivolumab (flat dose of 480 mg IV every four weeks as per standard clinical practice) after nivolumab plus ipilimumab induction as per standard clinical practice.

Centri partecipanti

Nord Italia

ASST Spedali Civili di Brescia
Piazzale Spedali Civili 1 - 25123 Brescia - BS

Riferimento: Prof. Alfredo Berruti
Email: oncologia@spedalicivili.brescia.it

 

ASST di Cremona
Viale Concordia 1 - 26100 Cremona - CR

 

IRCCS A.O.U. San Martino - IST
Largo Rosanna Benzi 10 - 16132 Genova - GE

Riferimento: Dr. Giuseppe Fornarini
Email: giuseppe.fornarini@hsanmartino.it

 

IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI
S.S. Oncologia Medica Genitorutinaria

Riferimento: Dr.ssa Elena Verzoni
Email: elena.verzoni@istitutotumori.mi.it

 

Istituto Europeo di Oncologia
Via Ripamonti 435 - 20141 Milano - MI

Riferimento: Dr. Franco Nolè
Email: franco.nole@ieo.it

 

Istituto Clinico Humanitas Rozzano
Via Manzoni 56 - 20089 Rozzano - MI

Riferimento: Prof. Paolo Zucali
Email: paolo.zucali@hunimed.eu

 

A.O.U. Policlinico di Modena
Via del Pozzo 71 - 41100 Modena - MO

 

A.O.U. Maggiore della Carità
Corso Mazzini 18 - 28100 Novara - NO

Riferimento: Dr. Carlo Cattrini
Email: carlo.cattrini@maggioreosp.novara.it

 

Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD

Riferimento: Dr. Davide Bimbatti
Email: davide.bimbatti@iov.veneto.it

 

Azienda Ospedaliero-Universitaria di Parma
Via Gramsci 14 - 43126 Parma - PR
Oncologia Medica

 

AUSL/IRCCS di Reggio Emilia
Viale Risorgimento 80 - 42123 Reggio nell'Emilia - RE

Riferimento: Dr.ssa Cristina Masini
Email: cristina.masini@ausl.re.it

 

IRCCS Candiolo (TO)
St.Provinciale Km 3,95 SP142 - 10060 Candiolo - TO

 

AOUI Verona - Borgo Roma
Piazzale Ludovico Antonio Scuro 10 - 37134 Verona - VR

 

Centro Italia

AOU Careggi
Largo Brambilla 3 - 50134 Firenze - FI

Riferimento: Prof. Lorenzo Antonuzzo
Email: antonuzzol@aou-careggi.toscana.it

 

AOU Pisana - Santa Chiara
Via Roma 67 - 56126 Pisa - PI

Riferimento: Dr. Luca Galli
Email: aiutopoint@ao-pisa.toscana.it

 

Fondazione Policlinico A. Gemelli
Largo Agostino Gemelli 8 - 00168 Roma - RM

Riferimento: Dr. Roberto Iacovelli
Email: roberto.iacovelli@policlinicogemelli.it

 

Istituto Nazionale Tumori “Regina Elena”
Via Elio Chianesi 53 - 00144 Roma - RM

 

Ospedale Belcolle
Strada Sammartinese - 01100 Viterbo - VT

 

Sud Italia e isole

AOU di Cagliari - Presidio Policlinico Monserrato
St.Statale 554, Km 4500 - 09100 Monserrato - CA

 

A.O. per l’Emergenza Cannizzaro di Catania
Via Messina 829 - 95126 Catania - CT

Riferimento: Dr.ssa Giuseppa Scandurra
Email: oncologia@ospedale-cannizzaro.it

 

Santa Maria delle Grazie - Pozzuoli
Via Domitiana - 80078 La Schiana - Pozzuoli - NA

Riferimento: Dr. Gaetano Facchini
Email: gaetano.facchini@aslnapoli2nord.it

 

AORN Cardarelli
Via A Cardarelli 9 - 80131 napoli - NA

Riferimento: Dr. Ferdinando Riccardi
Email: studiclinici.onco@aocardarelli.it

 

Casa di Cura La Maddalena
Via San Lorenzo Colli 312/d - 90146 Palermo - PA

 

A.O. S.Carlo
Via P. Petrone 1 - 85100 Potenza - PZ

Informazioni Generali

Protocollo

Numero di iscrizione a registro: NCT05817903

Data di inserimento: 11.03.2024

Promotore

Consorzio Oncotech

CRO

Clinical Research Technology

Principal Investigator ITALIA

Fondazione Policlinico A. Gemelli IRCCS

Riferimento: Dr. Roberto Iacovelli

Telefono: 00000

Email: roberto.iacovelli@policlinicogemelli.it

Localita: Roma

 

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