Phase II study of axitinib intensification plus standard of care (SOC) compared to SOC alone after induction with nivolumab plus ipilimumab in mRCC patients without previous complete response (AxIn study).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Consorzio Oncotech

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 May 2024 → ongoing

Decision date (initial)

2024-03-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer

External identifiers

EU CT number

2024-511397-70-00

EudraCT number

2022-001150-35

ClinicalTrials.gov

NCT05817903

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To investigate the efficacy of axitinib in patients eligible to receive the standard of care (SOC) after the induction with nivolumab plus ipilimumab in mRCC.

Secondary objectives 1

1. To investigate the safety and the activity of axitinib in patients eligible to receive the standard of care (SOC) after the induction with nivolumab plus ipilimumab in mRCC.

Conditions and MedDRA coding

metastatic renal cell carcinoma (mRCC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype and candidate to continue the standard of care with immunotherapy after nivolumab plus ipilimumab induction as per standard clinical practice. 2. Completion of at least 2 cycles of the induction of nivolumab and ipilimumab without nivolumab-related toxicity that cannot allow the continuation of nivolumab and no complete response or progressive disease. Treatment with SOC ± axitinib should be started within 12 weeks from last dose of nivolumab/ipilimumab.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: a) Absolute neutrophil count (ANC) = 1500/mm3 (= 1.5 GI/L) b) Platelets = 100,000/mm3 (= 100 GI/L). c) Haemoglobin = 9 g/dL (= 90 g/L). d) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × upper limit of normal. e) Total bilirubin = 1.5 × the upper limit of normal. For subjects with Gilbert’s disease = 3 mg/dL (= 51.3 µmol/L). f) 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

1. 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. 7. Concomitant anticoagulation at therapeutic doses with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel). These are not allowed in case of randomization in the experimental arm, enrollment is allowed if clinician and patient agree to switch to low-molecular-weight heparin (LMWH) in case of randomization to axitinib + SOC arm. No restrictions to anticoagulants is applied for patients randomized in the SOC arm alone.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 i 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 . 13. Vaccination within 4 weeks of the first dose of axitinib and while on trials is prohibited except for administration of inactivated vaccines. 14. Active autoimmune disease that might deteriorate when receiving an immunostimulatory 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, 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • To evaluate the overall response rate in patients treated with the axitinib in addiction to SOC compared to SOC alone.

Secondary endpoints 1

1. • To evaluate the efficacy of axitinib in addiction to SOC compared to SOC alone in terms of: a) Progression free survival b) Overall survival c) Depth of response d) Duration of response e) Quality of life • To evaluate the safety of axitinib in addiction to SOC compared to SOC alone

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Consorzio Oncotech

Sponsor organisation

Consorzio Oncotech

Address

Via Sergio Pansini 5

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

Consorzio Oncotech

Contact name

Roberto Iacovelli

Public contact point

Organisation

Consorzio Oncotech

Contact name

Roberto Iacovelli

Locations

2 EU/EEA countries · 45 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications