Clinical trial NCT04134390: Study of Cabozantinib Efficacy, Safety and Tolerability in Metastatic Renal Carcinoma in Aged Fragile Patients: CABOMAYOR Study
Official title: Pilot Study of Cabozantinib Efficacy, Safety and Tolerability in Metastatic Renal Carcinoma in Aged Fragile Patients: CABOMAYOR Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Old Age; Debility
Renal Carcinoma Metastatic
Keywords: fragile
renal carcinoma
old age
Lead sponsor: Spanish Oncology Genito-Urinary Group
Sponsor class: OTHER
Collaborators: name: Apices Soluciones S.L.
First posted: 2019-10-22
Enrollment: 25
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 24 months
measure: Objective Response Rate (ORR)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Up to 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 24 months
measure: Progression Free Survival (PFS)
timeFrame: Since the patient's study enrolment until patient progression, assessed up to 24 months
measure: Overall Survival (OS)
timeFrame: Since the patient's study enrolment until death assessed up to 24 months
Other outcomes:
Locations:
city: Ciudad Real
country: Spain
facility: Hospital de Ciudad Real
city: L'Hospitalet De Llobregat
country: Spain
facility: ICO L'Hospitalet
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Insular de Gran Canarias
city: Lugo
country: Spain
facility: Hospital Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Infanta Sofia
city: San Sebastián
country: Spain
facility: Hospital Universitario de Donostia
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: Hospital Doctor Peset
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Valladolid
country: Spain
facility: Hospital Clinico de Valladolid
Study officials:
affiliation: FIVO
name: Miguel A Climent, MD
role: PRINCIPAL_INVESTIGATOR
References: