Trial Title:
Axitinib Intensification Plus Nivolumab or Nivolumab Alone After Nivolumab Plus Ipilimumab in mRCC Patients
NCT ID:
NCT05817903
Condition:
Metastatic Renal Cell Carcinoma
Conditions: Official terms:
Carcinoma, Renal Cell
Nivolumab
Axitinib
Conditions: Keywords:
mRCC
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Participants are assigned to one of two groups (ARM A vs ARM B) in parallel for the
duration of the study.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Axitinib
Description:
Axitinib will be started at the standard dose of 5 mg BID until progression of disease,
unacceptable toxicity, patient' or physician' decision.
Arm group label:
ARM A
Other name:
Inlyta
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
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 group label:
ARM A
Arm group label:
ARM B
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.
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).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
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:
1. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L)
2. Platelets ≥ 100,000/mm3 (≥ 100 GI/L).
3. Haemoglobin ≥ 9 g/dL (≥ 90 g/L).
4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 ×
upper limit of normal.
5. Total bilirubin ≤ 1.5 × the upper limit of normal. For subjects with Gilbert's
disease ≤ 3 mg/dL (≤ 51.3 µmol/L).
6. 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.
Exclusion Criteria:
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:
1. Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac
arrhythmias.
2. Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic or > 100
mm Hg diastolic despite optimal antihypertensive treatment.
3. 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:
1. 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.
2. 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:
1. 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.
2. Serious non-healing wound/ulcer/bone fracture.
3. Malabsorption syndrome.
4. Uncompensated/symptomatic hypothyroidism.
5. Moderate to severe hepatic impairment (Child-Pugh B or C).
6. Requirement for hemodialysis or peritoneal dialysis.
7. History of solid organ transplantation.
8. In past 6 months: deep vein thrombosis or pulmonary embolism.
9. 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. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
ASST degli Spedali Civili di Brescia
Address:
City:
Brescia
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Alfredo Berruti
Email:
alfredo.berruti@gmail.com
Facility:
Name:
Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS
Address:
City:
Candiolo
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Alessandra Mosca
Email:
alessandra.mosca@ircc.it
Facility:
Name:
Azienda Ospedaliera per l'emergenza Cannizzaro
Address:
City:
Catania
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Giuseppa Scandurra
Email:
giusy.scandurra@gmail.com
Facility:
Name:
ASST di Cremona
Address:
City:
Cremona
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Maria Olga Giganti
Contact backup:
Email:
maria.giganti@asst-cremona.it
Facility:
Name:
Azienda Ospedaliero Universitaria Careggi
Address:
City:
Firenze
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Lorenzo Antonuzzo
Email:
lorenzo.antonuzzo@unifi.it
Facility:
Name:
Ospedale Policlinico San Martino
Address:
City:
Genova
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Giuseppe Fornarini
Email:
giuseppe.fornarini@hsanmartino.it
Facility:
Name:
Fondazione IRCCS - Istituto Nazionale dei Tumori
Address:
City:
Milano
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Elena Verzoni
Email:
elena.verzoni@istitutotumori.mi.it
Facility:
Name:
Istituto Europeo di Oncologia - IEO
Address:
City:
Milano
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Franco Nolè
Email:
franco.nole@ieo.it
Facility:
Name:
A.O.U. Policlinico di Modena
Address:
City:
Modena
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Roberto Sabbatini
Email:
sabbatini@unimore.it
Facility:
Name:
Policlinico Duilio Casula - Azienda Ospedaliero-Universitaria di Cagliari
Address:
City:
Monserrato
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Francesco Atzori
Email:
francescoatzori74@yahoo.it
Facility:
Name:
Azienda Ospedaliero-Universitaria Maggiore della Carità
Address:
City:
Novara
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Carlo Cattrini
Email:
carlo.cattrini@maggioreosp.novara.it
Facility:
Name:
Istituto Oncologico Veneto
Address:
City:
Padova
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Davide Bimbatti
Email:
davide.bimbatti@iov.veneto.it
Facility:
Name:
Casa Di Cura La Maddalena S.P.A.
Address:
City:
Palermo
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Vittorio Gebbia
Email:
vittorio.gebbia@gmail.com
Facility:
Name:
Azienda Ospedaliera Universitaria di Parma
Address:
City:
Parma
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Sebastiano Buti
Email:
sbuti@ao.pr.it
Facility:
Name:
Azienda Ospedalieo-Universitaria Pisana
Address:
City:
Pisa
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Luca Galli
Email:
lugal71@yahoo.it
Facility:
Name:
San Carlo - Azienda Ospedaliera Regionale
Address:
City:
Potenza
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Angelo Dinota
Email:
dinota@yahoo.com
Facility:
Name:
Presidio Ospedaliero S. Maria Delle Grazie
Address:
City:
Pozzuoli
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Gaetano Facchini
Email:
gaetano.facchini@aslnapoli2nord.it
Facility:
Name:
IRCCS - AUSL di Reggio Emilia
Address:
City:
Reggio Emilia
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Cristina Masini
Email:
cristina.masini@ausl.re.it
Facility:
Name:
Azienda Ospedaliera San Camillo Forlanini
Address:
City:
Romano Di Lombardia
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Fabio Calabrò
Email:
fcalabro@scamilloforlanini.rm.it
Facility:
Name:
Fondazione Policlinico Universitario A. Gemelli IRCCS
Address:
City:
Roma
Country:
Italy
Status:
Active, not recruiting
Facility:
Name:
IRCCS - Istituto Clinico Humanitas
Address:
City:
Rozzano
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Paolo Andrea Zucali
Email:
paolo.zucali@hunimed.eu
Facility:
Name:
Azienda Ospedaliera Universitaria Integrata Verona - Borgo Roma
Address:
City:
Verona
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Michele Milella
Email:
michele.milella@aovr.veneto.it
Facility:
Name:
Ospedale di Belcolle
Address:
City:
Viterbo
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Francesca Primi
Email:
fprimi@gmail.com
Start date:
April 18, 2023
Completion date:
April 1, 2027
Lead sponsor:
Agency:
Consorzio Oncotech
Agency class:
Other
Collaborator:
Agency:
Pfizer
Agency class:
Industry
Source:
Consorzio Oncotech
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05817903
