Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. The CABATEN Study

NCT04400474 | Completed Phase 2 Results DMC

• 2 other identifiers: GETNE-T19142019-002279-32
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 15

Brief Summary

CABATEN is a multicohort phase II study of cabozantinib plus atezolizumab in advanced and progressive tumors from endocrine system. The primary objective is to assess the efficacy of cabozantinib plus atezolizumab combination by means of radiological objective response rate (ORR) evaluated following RECIST v1.1 criteria in advanced endocrine tumors. Endocrine tumors from different origins (thyroid, lung, pancreas and digestive tract, adrenal gland and paraganglia) are characterized by being remarkably vascular and expressing several growth factors including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), basic fibroblast growth factor (BFGF), and transforming growth factor (TGF)-α and -β. The (over) expression of some of these factors has been linked to poor prognosis. Cabozaninib, a VEGF inhibitor, in combination with atezolizumab, an inhibitor of PD-L1, may be active in endocrine tumors by overcoming the resistance to prior antiangiogenic drugs. The trial will include patients with advanced and refractory tumors of endocrine system and patients would be allocated to six different cohorts according to the following tumor types.

Conditions

Neuroendocrine Tumor; Anaplastic Thyroid Cancer; Adenocarcinoma; Pheochromocytoma; Paraganglioma

Keywords

Cabozantinib; Atezolizumab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Radiological objective response rate (ORR) evaluated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan ORR= CR (confirmed complete response) + PR (confirmed partial response) as best response PR (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

  Through study completion, average 1 year

Secondary Outcomes (5)

• Safety Profile Number of Adverse Events Reactions (TRAEs)

  TRAEs reported through clinical, up to 100 days after finishing or discontinuing treatment, on average 10 months

• Safety Profile Number of Adverse Events Reactions (TRAEs) Related With Atezolizumab

  TRAEs reported through clinical, up to 100 days after finishing or discontinuing treatment, on average 10 months

• Duration of Response (DoR)

  From date of first documented clinical response (PR, CR) until the date of first documented progression, date of death from any cause or patient withdrawal, whichever came first, assessed up to 36 months

• Progression-free Survival (PFS)

  From date of randomization until the date of first documented progression, date of death from any cause or patient withdrawal, whichever came first, assessed up to 36 months

• Overall Survival (OS)

  Through study period, up to 3 years after completing treatment

Study Arms (1)

Cabozantinib 40 mg + Atezolizumab 1200 mg

EXPERIMENTAL

* Cabozantinib 40 mg tablets, oral administration, once daily, continuously. * Atezolizumab 1200 mg administered intravenously, every three weeks (cycle).

Drug: Cabozantinib 40 mg

Interventions

Cabozantinib 40 mg DRUG

All the subjects will be treated with the combination of cabozantinib and atezolizumab until disease progression, unacceptable toxicity or patient consent withdrawal (whichever occurs first).

Also known as: Atezolizumab 1200 mg

Cabozantinib 40 mg + Atezolizumab 1200 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects ≥ 18 years old.
• Willingness to participate in the study by signing informed consent form (ICF) approved by the trial Central Ethic Committee (CEIm).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Measurable disease per RECIST 1.1 as determined by the investigator.
• Patients with an histopathologically confirmed disease (as per local pathology report), meeting one of the following (according to WHO 2010 classification):
• Cohort 1: Well-differentiated neuroendocrine tumours of the lung and thymus (WHO grade 1 and 2, typical and atypical carcinoids) after progression to somatostatin analogs, targeted agents, PRRT, and/or chemotherapy.
• Cohort 2: Anaplastic thyroid cancer in first-line or after progression to chemotherapy or investigational drugs. Primary tumour can be resected or not but risk of aerodigestive compression or bleeding should be ruled out.
• Cohort 3: Adrenocortical carcinoma after progression to chemotherapy and/or mitotane.
• Cohort 4: Pheochromocytoma and paraganglioma after progression to peptide receptor radionuclide therapy (PRRT) if indicated. Prior chemotherapy and biological therapy, such as somatostatin analogs, are allowed.
• Cohort 5: Well-differentiated neuroendocrine tumours of digestive system (WHO grade 1 and 2) after progression to somatostatin analogs, targeted agents, PRRT, and/or chemotherapy.
• Cohort 6: Grade 3 neuroendocrine neoplasm (WHO grade 3, including neuroendocrine (NET) and neuroendocrine carcinomas (NEC) G3) of any origin, excluding small cell lung cancer, after progression to chemotherapy or targeted agents/PRRT.
• Recovery from toxicity related to any prior treatments to ≤ Grade 1, unless the adverse events (AEs) are clinically non-significant and/or stable on supportive therapy.
• Ability to swallow tablets.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥ 9.0 g/dL.

You may not qualify if:

• Prior treatment with cabozantinib or any immune checkpoint inhibitor therapy (e.g, CTLA4, PD-1, or PD-L1 targeting agent).
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives of the agent, whichever is longer. Patients should have been out of mitotane for at least 4 weeks.
• Receipt of any type of anticancer antibody (including investigational antibody) or systemic chemotherapy within 2 weeks before starting treatment.
• Current or prior use of immunosuppressive medication within 2 weeks before the first dose of cabozantinib and atezolizumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
• Active or prior documented autoimmune disease within the past 2 years. Note: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis).
• History of allogeneic organ transplant.
• Subjects having a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 28 days prior to the first dose of trial treatment.
• Concomitant anticoagulation with oral anticoagulants (e.g, warfarin, direct thrombin and factor Xa inhibitors) or platelet inhibitors (e.g, clopidogrel), except for the following allowed anticoagulants:
• Low-dose aspirin for cardioprotection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a. Cardiovascular disorders: i. Class 3 or 4 congestive heart failure as defined by the New York Heart Association, unstable angina pectoris, and serious cardiac arrhythmias.
• ii. Uncontrolled hypertension defined as sustained blood press \> 150 mm hg systolic or \> 100 mm hg diastolic despite optimal antihypertensive treatment.
• c. Clinically significant hematemesis or hemoptysis of \> 0.5 teaspoon (\> 2.5 ml) of red blood or history of other significant bleeding within 3 months before treatment.
• d. Cavitating pulmonary lesion(s) or known endobronchial disease manifestation. e. Lesions invading major pulmonary blood vessels. f. Other clinically significant disorders such as: i. Active infection requiring systemic treatment, infection with human immunodeficiency virus or acquired immunodeficiency syndrome-related illness, or chronic hepatitis B or C infection.

Sponsors & Collaborators

• Grupo Espanol de Tumores Neuroendocrinos: lead
• Ipsen: collaborator
• Roche Pharma AG: collaborator

Study Sites (15)

Hospital Germans Trias i Pujol - ICO Badalona

Badalona, Barcelona, 08916, Spain

Location

Hospital Duran i Reynals - ICO L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital General Universitario Elche

Alicante, 03010, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, 38320, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Neuroendocrine Tumors; Thyroid Carcinoma, Anaplastic; Adenocarcinoma; Pheochromocytoma; Paraganglioma

Interventions

cabozantinib; atezolizumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Carcinoma; Neoplasms, Glandular and Epithelial

Results Point of Contact

• Title: A responsibility person designate by sponsor
• Organization: MFAR

investigacion@mfar.net

934344412

Study Officials

• Jaume Capdevila, M.D, Ph.D

  Hospital Universitari Vall d'Hebron, Barcelona

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: May 22, 2020
• Study Start: October 7, 2020
• Primary Completion: November 23, 2023
• Study Completion: December 15, 2023
• Last Updated: June 19, 2025
• Results First Posted: June 19, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (15)