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

NCT04134390 | Completed Phase 2

• 2 other identifiers: CABOMAYOR2019-001639-30
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 10

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.

Conditions

Old Age; Debility; Renal Carcinoma Metastatic

Keywords

fragile; renal carcinoma; old age

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  Complete Response (CR) evaluated by Evaluation Criteria In Solid Tumors (RECIST) 1.1 according to investigator criteria.

  Up to 24 months

• Objective Response Rate (ORR)

  Partial Response (PR) evaluated by Evaluation Criteria In Solid Tumors (RECIST) 1.1 according to investigator criteria.

  Up to 24 months

Secondary Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events

  Up to 24 months

• Disease Control Rate (DCR)

  Up to 24 months

• Disease Control Rate (DCR)

  Up to 24 months

• Disease Control Rate (DCR)

  Up to 24 months

• Progression Free Survival (PFS)

  Since the patient's study enrolment until patient progression, assessed up to 24 months

Study Arms (1)

Cabozantinib

EXPERIMENTAL

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

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Subjects will receive cabozantinib 40mg p.o. as long as they continue to experience clinical benefit or until unacceptable toxicity, the need for alternative anticancer treatment, or other reasons for treatment discontinuation

Cabozantinib

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Documented histological or cytological diagnosis of renal cell cancer.
• Measurable disease per RECIST 1.1 as determined by the investigator.
• Metastatic disease.
• Patient must have signed the informed consent document.
• Capable of understanding and complying with the protocol requirements.
• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0-2.
• Patients aged \>70 years old with Society of Geriatric Oncology (SIOG) defined fragile population or patients \>75 years with or without SIOG defined fragility.
• No previous treatment for Metastatic Renal Cell Carcinoma (mRCC)
• Adequate organ function based on standard laboratory tests including haematology, serum chemistry, lipids, coagulation, thyroid function, and urinalysis.
• 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.

You may not qualify if:

• Previous treatment for mRCC.
• Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors or low molecular weight heparins (LMWH).
• Chronic treatment with corticosteroids or other immunosuppressive agents
• Inability to swallow tablets or capsules.
• Previously identified allergy or hypersensitivity to components of the study treatment formulation.

Sponsors & Collaborators

• Spanish Oncology Genito-Urinary Group: lead
• Apices Soluciones S.L.: collaborator

Study Sites (10)

Hospital de Ciudad Real

Ciudad Real, Spain

Location

ICO L'Hospitalet

L'Hospitalet de Llobregat, Spain

Location

Hospital Insular de Gran Canarias

Las Palmas de Gran Canaria, Spain

Location

Hospital Lucus Augusti

Lugo, Spain

Location

Hospital Infanta Sofia

Madrid, Spain

Location

Hospital Universitario de Donostia

San Sebastián, Spain

Location

Fundación Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Hospital Doctor Peset

Valencia, Spain

Location

Hospital Universitario La Fe

Valencia, Spain

Location

Hospital Clinico de Valladolid

Valladolid, Spain

Location

MeSH Terms

Conditions

Frailty; Carcinoma, Renal Cell

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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

Study Officials

• Miguel A Climent, MD

  FIVO

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Cabozantinib 40 mg per os (p.o.) once daily in 28-day cycles. Dose can be escalated to 60 mg to avoid suboptimal exposure to the drug if 40 mg is considered tolerated. If the dose of 40 mg is not tolerated, a de-escalation to 20 mg, temporary interruption, or stopping cabozantinib will be possible.

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 22, 2019
• Study Start: February 17, 2020
• Primary Completion: November 22, 2023
• Study Completion: November 22, 2023
• Last Updated: January 9, 2024

Record last verified: 2023-12

Locations

ES (10)