Neuroendocrine TumorPhase 2CABATENNCT04400474
Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. The CABATEN Study
A Phase 2 study testing Cabozantinib 40 mg in people with Neuroendocrine Tumor and Anaplastic Thyroid Cancer, run by Grupo Espanol de Tumores Neuroendocrinos at 15 sites in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumor, Anaplastic Thyroid Cancer, Adenocarcinoma
- What is being tested?
- Cabozantinib 40 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 15 sitesSpain
- Study dates
- 7 Oct 2020to 15 Dec 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 23Show fewer
- 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.
- Absolute neutrophil count (ANC) > 1500 per mm.
- Platelet count ≥ 100,000 per mm.
- Serum bilirubin ≤ 1.5x institutional upper limit of normal (ULN) unless liver metastases are present, in which case it must be ≤ 2X ULN. This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology); however, they will be allowed only in consultation with their physician.
- Aspartate Transaminase (AST) (SGOT)/Alanine aminotransferase (ALT) (SGPT) ≤ 2.5x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 3x ULN.
- Measured creatinine clearance (CL) > 40 mL/min or Calculated creatinine CL > 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for the determination of creatinine clearance.
- Female subjects of childbearing potential (not surgically sterile or at least 2 years postmenopausal) must provide a negative urine pregnancy test at Screening, and use a medically accepted double barrier method of contraception (i.e condom with spermicide + IUD or cervical caps). In addition, they must agree to continue the use of this double barrier method for the duration of the study and for 4 months after participation in the study.
- Males should agree to abstain from sexual intercourse with a female partner or agree to use a double barrier method of contraception (i.e.condom with spermicide, in addition to having their female partner use some contraceptive measures such as, intrauterine device (IUD) or cervical caps), for the duration of the study and for 4 months after participation in the study.
- Willingness and ability of patients to comply with the protocol for the duration of the study including undergoing treatment as well as availability for scheduled visits and examinations including follow up.
Who cannot join
- 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).
Show all 28Show fewer
- 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.
- Receipt of radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before inclusion. Subjects with clinically relevant ongoing complications from prior radiation therapy that have not completely resolved are not eligible (e.g, radiation esophagitis or other inflammation of the viscera).
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before inclusion. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of study 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).
- Anticoagulation with therapeutic doses of LMWH in subjects without known brain metastases and who are on a stable dose of LMWH for at least 6 weeks before inclusion and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumour.
- The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- 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.
- Uncontrolled hypertension defined as sustained blood press > 150 mm hg systolic or > 100 mm hg diastolic despite optimal antihypertensive treatment.
- Stroke, including transient ischemic attack (TIA), myocardial infarction, other ischemic event, or thromboembolic event, e.g, deep venous thrombosis (DVT) and pulmonary embolism) within 6 months before inclusion. Subjects with a more recent diagnosis of DVT are allowed if stable, asymptomatic, and treated with LMWH for at least 6 weeks before study treatment.
- Gastrointestinal disorders (e.g, malabsorption syndrome or gastric outlet obstruction) including those associated with a high risk of perforation or fistula formulation: i. Tumours invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction. ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before inclusion. Note: complete healing of an intra-abdominal abscess must be confirmed prior to start of the treatment.
- 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.
- 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.
- Serious non-healing wound/ulcer/bone fracture. iii. Moderate to severe hepatic impairment (child-pugh B or C). iv. Requirement for hemodialysis or peritoneal dialysis. v. Uncontrolled diabetes mellitus. vi. History of solid organ transplantation.
- Major surgery (e.g, GI surgery and removal or biopsy of brain metastasis) within 8 weeks before inclusion. Complete wound healing from major surgery must have occurred 4 weeks before study treatment and from minor surgery (e.g, simple excision, tooth extraction) at least 10 days before study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
- Corrected QT interval calculated by the Fridericia formula (QTcf) > 500 ms within 28 days before study treatment.
- Note: if a single ECG shows a QTCf with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these 3 consecutive results for qtcf will be used to determine eligibility.
- Pregnant or lactating females.
- Inability to swallow tablets.
- Previously identified allergy or hypersensitivity to components of the study treatment formulations.
- Diagnosis of another malignancy within 3 years before study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
Spain15 sites
Hospital General Universitario Elche
Alicante, 03010
Hospital Germans Trias i Pujol - ICO Badalona
Badalona, Barcelona, 08916
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Duran i Reynals - ICO L'Hospitalet
L'Hospitalet de Llobregat, Barcelona, 08908
MD Anderson Cancer Center
Madrid, 28033
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Hospital General Universitario Morales Meseguer
Murcia, 30008
Hospital Universitario Central de Asturias
Oviedo, 33011
Hospital Universitario de Canarias
Santa Cruz de Tenerife, 38320
Hospital Universitario Marqués de Valdecilla
Santander, 39008
Hospital Universitario Virgen del Rocío
Seville, 41013
Hospital Universitario Miguel Servet
Zaragoza, 50009
About this study
Official title: Exploratory Basket Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. CABATEN Study
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.
Read more
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.
Read the detailed description
CABATEN is a multicohort phase II study of cabozantinib plus atezolizumab in advanced and progressive tumors from endocrine system.
Hypothesis:
The main hypothesis is that the administration of cabozantinib plus atezolizumab will improve the probability of expected objective response rate in advanced and refractory tumors of the endocrine system.
Objectives:
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. Secondary objectives include:
- To evaluate the safety profile of cabozantinib and atezolizumab combination, according to NCI-CTCAE V5.0.
- Duration of response (DoR) as per RECIST V1.1.
- Progression-free survival (PFS): median PFS as per RECIST V1.1.
- Overall Survival (OS): median OS as per RECIST V1.1.
- Tumor biomarkers: translational sub-study (optional).
Treatment:
All the subjects will be treated with the combination until disease progression, unacceptable toxicity, or patient consent withdrawal (whichever occurs first):
- Cabozantinib 40 mg or 20 mg tablets, oral administration once daily continuously.
- Atezolizumab 1200 mg administered intravenously (IV) every three weeks (cycle).
Rationale:
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.
Patients allocation:
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:
Cohort 1: Well-differentiated neuroendocrine tumors of the lung and thymus (grades 1 and 2) 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.
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 tumors of digestive system after progression to somatostatin analogs, targeted agents, PRRT, and/or chemotherapy.
Cohort 6: Grade 3 neuroendocrine neoplasm of any origin, excluding small cell lung cancer, after progression to chemotherapy or targeted agents/PRRT.
- Conditions
- Neuroendocrine Tumor, Anaplastic Thyroid Cancer, Adenocarcinoma, Pheochromocytoma, Paraganglioma
- Being tested
- Cabozantinib 40 mg
- Keywords
- Cabozantinib, Atezolizumab
- Medical subject headings
- Neuroendocrine Tumors, Thyroid Carcinoma, Anaplastic, Adenocarcinoma, Pheochromocytoma, Paraganglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cabozantinib 40 mgDrug
Also called Atezolizumab 1200 mg
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).
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Cabozantinib 40 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, average 1 year
Secondary outcomes (5)
Safety Profile Number of Adverse Events Reactions (TRAEs)
Number of patients adverse events reaction (TRAEs) related to Cabozantinib
Measured: 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
Number of patients with adverse events reaction related to Atezolizumab as assessed by CTCAE v4.0
Measured: TRAEs reported through clinical, up to 100 days after finishing or discontinuing treatment, on average 10 months
Duration of Response (DoR)
the time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer. DoR will be determined based on tumour assessment (RECIST version 1.1 criteria).
Measured: 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)
Median Progression free survival (mPFS) is defined as the time from the date of inclusion to the date of the first documented disease progression or death due to any cause, whichever occurs first. PFS will be determined based on tumour assessment (RECIST version 1.1 criteria). The local Investigator's assessments will be used for analyses.
Measured: 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)
Median Overall Survival (mOS) is calculated as the time from date of inclusion to date of death due to any cause.
Measured: Through study period, up to 3 years after completing treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2020
- Study start7 Oct 2020
- Primary completion23 Nov 2023
- Study completion15 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuroendocrine TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol de Tumores Neuroendocrinos
- Sponsor type
- University, hospital or other
- Collaborators
- Ipsen, Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- Jaume Capdevila, M.D, Ph.D, Study chair, Hospital Universitari Vall d'Hebron, Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04400474
- Sponsor's protocol ID
- GETNE-T1914
- Other IDs
- 2019-002279-32, 2019
- Acronym
- CABATEN
- Status last verified
- May 2025
- First submitted
- 12 May 2020
- Last updated
- 19 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Basket Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. CABATEN Study
- ClinicalTrials.gov ID
- NCT04400474
- Acronym / sponsor ID
- CABATEN / GETNE-T1914
- Conditions
- Neuroendocrine Tumor, Anaplastic Thyroid Cancer, Adenocarcinoma, Pheochromocytoma, Paraganglioma
- Keywords
- Cabozantinib, Atezolizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Grupo Espanol de Tumores NeuroendocrinosUniversity, hospital or other
- Collaborators
- Ipsen, Roche Pharma AG
- Study start
- 7 Oct 2020 (actual)
- Primary completion
- 23 Nov 2023 (actual)
- Study completion
- 15 Dec 2023 (actual)
- First posted
- 22 May 2020 (actual)
- Results
- Posted 19 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
CABATEN is a multicohort phase II study of cabozantinib plus atezolizumab in advanced and progressive tumors from endocrine system.
Hypothesis:
The main hypothesis is that the administration of cabozantinib plus atezolizumab will improve the probability of expected objective response rate in advanced and refractory tumors of the endocrine system.
Objectives:
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. Secondary objectives include:
- To evaluate the safety profile of cabozantinib and atezolizumab combination, according to NCI-CTCAE V5.0.
- Duration of response (DoR) as per RECIST V1.1.
- Progression-free survival (PFS): median PFS as per RECIST V1.1.
- Overall Survival (OS): median OS as per RECIST V1.1.
- Tumor biomarkers: translational sub-study (optional).
Treatment:
All the subjects will be treated with the combination until disease progression, unacceptable toxicity, or patient consent withdrawal (whichever occurs first):
- Cabozantinib 40 mg or 20 mg tablets, oral administration once daily continuously.
- Atezolizumab 1200 mg administered intravenously (IV) every three weeks (cycle).
Rationale:
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.
Patients allocation:
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:
Cohort 1: Well-differentiated neuroendocrine tumors of the lung and thymus (grades 1 and 2) 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.
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 tumors of digestive system after progression to somatostatin analogs, targeted agents, PRRT, and/or chemotherapy.
Cohort 6: Grade 3 neuroendocrine neoplasm of any origin, excluding small cell lung cancer, after progression to chemotherapy or targeted agents/PRRT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cabozantinib 40 mg + Atezolizumab 1200 mg | Experimental | Drug: Cabozantinib 40 mg* Cabozantinib 40 mg tablets, oral administration, once daily, continuously. * Atezolizumab 1200 mg administered intravenously, every three weeks (cycle). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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):
Key exclusion criteria (28 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cabozantinib 40 mgAlso: Atezolizumab 1200 mgAll the subjects will be treated with the combination of cabozantinib and atezolizumab until disease progression, unacceptable toxicity or patient consent withdrawal (whichever occurs first). | Drug | Cabozantinib 40 mg + Atezolizumab 1200 mg |
Primary outcome
Objective Response Rate (ORR)
Time frame: Through study completion, average 1 year
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.
5 secondary outcomes
Safety Profile Number of Adverse Events Reactions (TRAEs)
Time frame: 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
Time frame: TRAEs reported through clinical, up to 100 days after finishing or discontinuing treatment, on average 10 months
Duration of Response (DoR)
Time frame: 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)
Time frame: 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)
Time frame: Through study period, up to 3 years after completing treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaume Capdevila, M.D, Ph.D study chair
Hospital Universitari Vall d'Hebron, Barcelona
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cabozantinib 40 mg in people with Neuroendocrine Tumor and Anaplastic Thyroid Cancer, run by Grupo Espanol de Tumores Neuroendocrinos at 15 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Through study completion, average 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2025.