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Metastatic Renal Cell CarcinomaPhase 2AxInNCT05817903

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

A Phase 2 study testing Axitinib and Nivolumab in people with Metastatic Renal Cell Carcinoma, run by Consorzio Oncotech at 23 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
Axitinib and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
118 participants
Where
23 sitesItaly
Study dates
18 Apr 2023to 1 Apr 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • 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.
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  • 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.
  • 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.

Who cannot join

  • Prior treatment with systemic therapy for advanced RCC with the exclusion of the induction of nivolumab and ipilimumab.
  • 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.
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  • 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:
  • 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.
  • 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.
  • 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.
  • Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
  • Lesions invading major pulmonary blood vessels.
  • 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
  • Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 3 months before the start of treatment. 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.
  • 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.
  • Vaccination within 4 weeks of the first dose of nivolumab and while on trials is prohibited except for administration of inactivated vaccines.
  • 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.
  • 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).
  • 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.
  • Has illness or medical conditions that are unstable or could jeopardize the safety of the patient and his or her compliance in the study.
  • Pregnant or lactating females.
  • Inability to swallow tablets or capsules.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  • Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Trial locations and contacts

23 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Roberto Iacovelli, MD contact

+393339516295

roberto.iacovelli@policlinicogemelli.it

Axin Service contact

axin@oncotech.org

23 sites in 1 country

Italy23 sites, 22 recruiting

  • ASST degli Spedali Civili di Brescia

    Brescia

    Alfredo Berruti, alfredo.berruti@gmail.com

    Not yet recruiting

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

    Candiolo

    Alessandra Mosca, alessandra.mosca@ircc.it

    Not yet recruiting

  • Azienda Ospedaliera per l'emergenza Cannizzaro

    Catania

    Giuseppa Scandurra, giusy.scandurra@gmail.com

    Not yet recruiting

  • ASST di Cremona

    Cremona

    Maria Olga Giganti

    maria.giganti@asst-cremona.it

    Not yet recruiting

  • Azienda Ospedaliero Universitaria Careggi

    Florence

    Lorenzo Antonuzzo, lorenzo.antonuzzo@unifi.it

    Not yet recruiting

  • Ospedale Policlinico San Martino

    Genova

    Giuseppe Fornarini, giuseppe.fornarini@hsanmartino.it

    Not yet recruiting

  • Fondazione IRCCS - Istituto Nazionale dei Tumori

    Milan

    Elena Verzoni, elena.verzoni@istitutotumori.mi.it

    Not yet recruiting

  • Istituto Europeo di Oncologia - IEO

    Milan

    Franco Nolè, franco.nole@ieo.it

    Not yet recruiting

  • A.O.U. Policlinico di Modena

    Modena

    Roberto Sabbatini, sabbatini@unimore.it

    Not yet recruiting

  • Policlinico Duilio Casula - Azienda Ospedaliero-Universitaria di Cagliari

    Monserrato

    Francesco Atzori, francescoatzori74@yahoo.it

    Not yet recruiting

  • Azienda Ospedaliero-Universitaria Maggiore della Carità

    Novara

    Carlo Cattrini, carlo.cattrini@maggioreosp.novara.it

    Not yet recruiting

  • Istituto Oncologico Veneto

    Padova

    Davide Bimbatti, davide.bimbatti@iov.veneto.it

    Recruiting

  • Casa Di Cura La Maddalena S.P.A.

    Palermo

    Vittorio Gebbia, vittorio.gebbia@gmail.com

    Not yet recruiting

  • Azienda Ospedaliera Universitaria di Parma

    Parma

    Sebastiano Buti, sbuti@ao.pr.it

    Not yet recruiting

  • Azienda Ospedalieo-Universitaria Pisana

    Pisa

    Luca Galli, lugal71@yahoo.it

    Not yet recruiting

  • San Carlo - Azienda Ospedaliera Regionale

    Potenza

    Angelo Dinota, dinota@yahoo.com

    Not yet recruiting

  • Presidio Ospedaliero S. Maria Delle Grazie

    Pozzuoli

    Gaetano Facchini, gaetano.facchini@aslnapoli2nord.it

    Not yet recruiting

  • IRCCS - AUSL di Reggio Emilia

    Reggio Emilia

    Cristina Masini, cristina.masini@ausl.re.it

    Not yet recruiting

  • Fondazione Policlinico Universitario A. Gemelli IRCCS

    Roma

    Active, not recruiting

  • Azienda Ospedaliera San Camillo Forlanini

    Romano di Lombardia

    Fabio Calabrò, fcalabro@scamilloforlanini.rm.it

    Not yet recruiting

  • IRCCS - Istituto Clinico Humanitas

    Rozzano

    Paolo Andrea Zucali, paolo.zucali@hunimed.eu

    Not yet recruiting

  • Azienda Ospedaliera Universitaria Integrata Verona - Borgo Roma

    Verona

    Michele Milella, michele.milella@aovr.veneto.it

    Not yet recruiting

  • Ospedale di Belcolle

    Viterbo

    Francesca Primi, fprimi@gmail.com

    Not yet recruiting

Other trials in Italy

About this study

Official title: 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 (AxIn Study).

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.

Read the detailed description

The present study aims to demonstrate if the addition of axitinib to nivolumab maintenance after nivolumab plus ipilimumab induction can improve the rate of response considering that the incidence of partial response was 32% and 51% in Checkmate214 and Keynote426 trials respectively.

This study requires 106 patients to show an improvement from 30% to 50% of the incidence of partial responses with a power of 80%, and alpha-error 0.10 (one-side p).

Assuming a drop out of 10%, the final estimated number to enroll should be 118 (59 in arm A and 59 in arm B).

Being tested
Axitinib, Nivolumab
Keywords
mRCC
Medical subject headings
Carcinoma, Renal Cell

What participants receive

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

  • AxitinibDrug

    Also called Inlyta

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

  • NivolumabDrug

    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

Study groups in NCT05817903
Study groupRoleWhat they receive
ARM AExperimentalAxitinib (starting dose 5 mg BID orally) in addition to nivolumab (lat dose of 480 mg IV every four weeks as per standard clinical practice)
Receives: Drug: Axitinib; Drug: Nivolumab
ARM BActive comparatorNivolumab (flat dose of 480 mg IV every four weeks as per standard clinical practice) after nivolumab plus ipilimumab induction as per standard clinical practice
Receives: Drug: Nivolumab

What is being measured

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

  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.

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

Secondary outcomes (6)

  1. Progression free survival (PFS)

    The PFS is defined as the time interval from the date of randomization to the date of radiological or clinical progression or death due to any cause. PFS will be reported as the median value and estimated by Kaplan-Meier method, difference between the two arms will be assessed by log-rank test.

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

  2. Overall survival (OS)

    The OS is defined as the time interval from the date of randomization to the date of death due to any cause. OS will be reported as the median value and estimated by Kaplan-Meier method, difference between the two arms will be assessed by log-rank test.

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

  3. Depth of response.

    The depth of response is defined as the number of patients who achieved different grades of tumor reduction between the two arms. Difference in the depth of response between will be reported as absolute number and percentage and difference between the two groups will be analyzed.

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

  4. Duration of response (DOR).

    The DOR is the length of time that a tumor continues to respond to treatment without the cancer growing or spreading. DOR will be reported as the median value and estimated by Kaplan-Meier method, difference between the two arms will be assessed by log-rank test.

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

  5. Health status and life status

    Quality of life will be evaluated by FKSI-19 and EQ-5D-5L questionnaires within 3 days prior the first study treatment, the first day of each cycle (1, 3, 5, etc.) of nivolumab prior to treatment administration, at the end of treatment visit.

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

  6. incidence of Treatment-Emergent Adverse Events, Serious adverse events and events of clinical interest, as assessed by the Investigators

    This analysis will include all the adverse events occurring from the randomization to 100 days after the last dose of drug. Incidence of adverse events will be reported as absolute number and percentage and difference between the two groups will be analyzed.

    Measured: all the adverse events occurring from the randomization to 100 days after the last dose of drug

Timeline

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

  1. First posted18 Apr 2023
  2. Study start18 Apr 2023
  3. Primary completion1 Apr 2026 (estimated)
  4. Study completion1 Apr 2027 (estimated)

Resources

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
Randomised
Intervention model
Parallel groups
Model description
Participants are assigned to one of two groups (ARM A vs ARM B) in parallel for the duration of the study.
Masking
None (open label)
Enrolment
118 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05817903
Sponsor's protocol ID
AxIn
Acronym
AxIn
Status last verified
May 2023
First submitted
14 Mar 2023
Last updated
8 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Axitinib and Nivolumab in people with Metastatic Renal Cell Carcinoma, run by Consorzio Oncotech at 23 sites in Italy.

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 16 inclusion and 41 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: looking for participants now, as of the sponsor's last update on 8 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Roberto Iacovelli, MD (+393339516295, roberto.iacovelli@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of axitinib in addition to nivolumab compared to nivolumab alone at the end of the induction with nivolumab plus ipilimumab in mRCC. (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first). 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 NCT05817903.

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 8 May 2023.

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