Study of Cabozantinib Efficacy, Safety and Tolerability in Metastatic Renal Carcinoma in Aged Fragile Patients: CABOMAYOR Study

Phase 2

Completed

• Conditions: Old Age; Debility; Renal Carcinoma Metastatic
• Interventions: Drug: Cabozantinib

• Registration Number: NCT04134390
• Lead Sponsor: Spanish Oncology Genito-Urinary Group

Brief Summary

Aged fragile patients are not usually included in clinical trials and efficacy and tolerability of the different available treatments in this population are unknown.

Conversely, ageing has been associated with a decrease in the efficacy of immune checkpoint inhibitors due to a decline in the effectiveness of the immune system (immunosenescence). In the Checkmate 025 trial comparing nivolumab with everolimus, the Hazard Ratio (HR) in patients older than 75 years old favoured everolimus, 1.23 (0.66-2.31). Thus, TKis might be a better treatment option for this population. However, the absence of data and concerns about possible secondary effects associated, can preclude clinicians to treat aged fragile patients with cabozantinib. A pilot phase II trial would help to have data on safety and efficacy of cabozantinib in this aged fragile population.

In METEOR trial around 60% of patients reduced the dose of cabozantinib because of toxicity and tolerance problems. It is suspected that the efficacy of cabozantinib in the population to be included in this trial (aged and fragile) will be similar to that observed in CABOSUN trial (disease control rate around 75%). However, there is no information available in this group of patients. On the other hand, in the \>75 years old subgroup within the METEOR trial, 37% discontinued due to adverse events, 85% needed dose reductions and median average daily dose was 33,6 mg. For this reason, the cabozantinib initial dose chosen for patients to be included in this study is 40 mg/day.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-15
• Study First Submitted QC: 2019-10-17
• Study First Posted: 2019-10-22
• Study Start: 2020-02-17
• Primary Completion: 2023-11-22
• Study Completion: 2023-11-22
• Status Verified: 2023-12
• Last Update Submitted: 2024-01-08
• Last Update Posted: 2024-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. Documented histological or cytological diagnosis of renal cell cancer.
2. Measurable disease per RECIST 1.1 as determined by the investigator.
3. Metastatic disease.
4. Patient must have signed the informed consent document.
5. Capable of understanding and complying with the protocol requirements.
6. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0-2.
7. Patients aged >70 years old with Society of Geriatric Oncology (SIOG) defined fragile population or patients >75 years with or without SIOG defined fragility.
8. No previous treatment for Metastatic Renal Cell Carcinoma (mRCC)
9. Adequate organ function based on standard laboratory tests including haematology, serum chemistry, lipids, coagulation, thyroid function, and urinalysis.
10. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.

Exclusion Criteria

1. Previous treatment for mRCC.
2. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before inclusion.
3. Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 3 months before inclusion.
4. Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors or low molecular weight heparins (LMWH).
5. Chronic treatment with corticosteroids or other immunosuppressive agents
6. Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: Cardiovascular disorders, Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation, Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 3 months before inclusion, Cavitating pulmonary lesion(s) or known endobronchial disease manifestation and/or Lesions invading major pulmonary blood vessels.
7. Major surgery within 2 months before inclusion.
8. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 msec within 10 days before inclusion.
9. Inability to swallow tablets or capsules.
10. Previously identified allergy or hypersensitivity to components of the study treatment formulation.
11. Diagnosis of another malignancy within 2 years before inclusion, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cabozantinib	Cabozantinib	Cabozantinib 40 mg p.o. once daily in 28-day cycles.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to 24 months	Partial Response (PR) evaluated by Evaluation Criteria In Solid Tumors (RECIST) 1.1 according to investigator criteria.

Secondary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	Up to 24 months	Adverse Events (AEs) experienced by patients. AEs will be assessed according to National Cancer Institute-Common Terminology Criteria (NCI-CTC) v 5.0 criteria.
Disease Control Rate (DCR)	Up to 24 months	Stable Disease (SD) evaluated by RECIST 1.1 criteria according to investigator criteria.
Overall Survival (OS)	Since the patient's study enrolment until death assessed up to 24 months	It is time in months since the patient's study enrolment until death
Progression Free Survival (PFS)	Since the patient's study enrolment until patient progression, assessed up to 24 months	Time in months since the patient's study enrolment until patient progression according to RECIST 1.1 criteria

Trial Locations

Locations (10)

Hospital Insular de Gran Canarias; 🇪🇸 Las Palmas De Gran Canaria, Spain

Hospital Lucus Augusti; 🇪🇸 Lugo, Spain

Hospital Infanta Sofia; 🇪🇸 Madrid, Spain

Hospital de Ciudad Real; 🇪🇸 Ciudad Real, Spain

ICO L'Hospitalet; 🇪🇸 L'Hospitalet De Llobregat, Spain

Fundación Instituto Valenciano de Oncologia; 🇪🇸 Valencia, Spain

Hospital Universitario de Donostia; 🇪🇸 San Sebastián, Spain

Hospital Universitario La Fe; 🇪🇸 Valencia, Spain

Hospital Clinico de Valladolid; 🇪🇸 Valladolid, Spain

Hospital Doctor Peset; 🇪🇸 Valencia, Spain