Axitinib Intensification Plus Nivolumab or Nivolumab Alone After Nivolumab Plus Ipilimumab in mRCC Patients

NCT05817903 | Recruiting Phase 2

• 1 other identifier: AxIn
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 23

Brief Summary

This phase II open label trial randomized patients who completed the induction with nivolumab plus ipilimumab without complete response or progressive disease will be randomized 1:1 to receive axitinib in addition to nivolumab (Arm A) or continue with nivolumab alone (Arm B).Treatment will be continued until progression of disease, unacceptable toxicity, patient's refusal, or physician decision whichever occurred first.

Conditions

Metastatic Renal Cell Carcinoma

Keywords

mRCC

Outcome Measures

Primary Outcomes (1)

• Efficacy of axitinib in addition to nivolumab compared to nivolumab alone at the end of the induction with nivolumab plus ipilimumab in mRCC.

  The response rate will be evaluated as the number of patients with complete or partial response in each arm. Response rate will be evaluated using RECIST 1.1 criteria.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first

Secondary Outcomes (6)

• Progression free survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first

• Overall survival (OS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first

• Depth of response.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first

• Duration of response (DOR).

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first

• Health status and life status

  From date of enrollment until the date of first documented progression or date of death from any cause

Other Outcomes (1)

• expression of PD-L1, PBRM1, CD31 on tumor cells ad CD8+ on lymphocytes

  24 months

Study Arms (2)

ARM A

EXPERIMENTAL

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)

Drug: Axitinib; Drug: Nivolumab

ARM B

ACTIVE COMPARATOR

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

Drug: Nivolumab

Interventions

Axitinib DRUG

Axitinib will be started at the standard dose of 5 mg BID until progression of disease, unacceptable toxicity, patient' or physician' decision.

Also known as: Inlyta

ARM A

Nivolumab DRUG

Nivolumab will be administered at a flat dose of 480 mg IV every four weeks until progression of disease, unacceptable toxicity, patient' or physician' decision

ARM A; ARM B

Eligibility Criteria

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

You may qualify if:

• 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.
• Completion of the induction of nivolumab and ipilimumab without toxicity ≥ G2 and no complete response or progressive disease.
• Male or female subjects aged ≥ 18 years
• Available tumor tissue sample.
• At least one measurable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group performance status 0 or 1.
• 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.
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
• 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.

You may not qualify if:

• Prior adjuvant or neoadjuvant therapy
• Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis
• 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.
• 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.
• 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.
• Concomitant anticoagulation at therapeutic doses with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel).
• In past 6 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack.
• 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.
• 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.

Sponsors & Collaborators

• Consorzio Oncotech: lead
• Pfizer: collaborator

Study Sites (23)

ASST degli Spedali Civili di Brescia

Brescia, Italy

NOT YET RECRUITING

Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS

Candiolo, Italy

NOT YET RECRUITING

Azienda Ospedaliera per l'emergenza Cannizzaro

Catania, Italy

NOT YET RECRUITING

ASST di Cremona

Cremona, Italy

NOT YET RECRUITING

Azienda Ospedaliero Universitaria Careggi

Florence, Italy

NOT YET RECRUITING

Ospedale Policlinico San Martino

Genova, Italy

NOT YET RECRUITING

Fondazione IRCCS - Istituto Nazionale dei Tumori

Milan, Italy

NOT YET RECRUITING

Istituto Europeo di Oncologia - IEO

Milan, Italy

NOT YET RECRUITING

A.O.U. Policlinico di Modena

Modena, Italy

NOT YET RECRUITING

Policlinico Duilio Casula - Azienda Ospedaliero-Universitaria di Cagliari

Monserrato, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Maggiore della Carità

Novara, Italy

NOT YET RECRUITING

Istituto Oncologico Veneto

Padua, Italy

RECRUITING

Casa Di Cura La Maddalena S.P.A.

Palermo, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria di Parma

Parma, Italy

NOT YET RECRUITING

Azienda Ospedalieo-Universitaria Pisana

Pisa, Italy

NOT YET RECRUITING

San Carlo - Azienda Ospedaliera Regionale

Potenza, Italy

NOT YET RECRUITING

Presidio Ospedaliero S. Maria Delle Grazie

Pozzuoli, Italy

NOT YET RECRUITING

IRCCS - AUSL di Reggio Emilia

Reggio Emilia, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera San Camillo Forlanini

Romano di Lombardia, Italy

NOT YET RECRUITING

IRCCS - Istituto Clinico Humanitas

Rozzano, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Integrata Verona - Borgo Roma

Verona, Italy

NOT YET RECRUITING

Ospedale di Belcolle

Viterbo, Italy

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Axitinib; Nivolumab

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Roberto Iacovelli

  Fondazione Policlinico "A. Gemelli", Università Cattolica Sacro Cuore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roberto Iacovelli, MD

CONTACT

+393339516295; roberto.iacovelli@policlinicogemelli.it

Axin Service

CONTACT

axin@oncotech.org

Study Design

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

Model Details: Participants are assigned to one of two groups (ARM A vs ARM B) in parallel for the duration of the study.

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: April 18, 2023
• Study Start: April 18, 2023
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: May 8, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (23)