Phase 3 CABINET Clinical Trial – Cabozantinib for Advanced Neuroendocrine Tumours

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Exelixis Announces Remarkable Efficacy in CABINET Trial for Advanced Neuroendocrine Tumors

On August 24, 2023, Exelixis made an exciting announcement regarding the Phase 3 CABINET pivotal trial. This trial focused on evaluating the effectiveness of cabozantinib in treating advanced pancreatic and extra-pancreatic neuroendocrine tumors. The CABINET trial was a significant undertaking, involving multiple centers and enrolling a total of 290 patients who were divided into two groups.

The trial progressed smoothly, but to everyone’s surprise, it was stopped early. The reason for this premature conclusion was the remarkable improvement in efficacy observed. The Alliance for Clinical Trials in Oncology independent Data and Safety Monitoring Board unanimously recommended ending the trial due to these unprecedented results.

“CABINET trial will be unblinded and stopped early due to a dramatic improvement in efficacy per a unanimous recommendation by The Alliance for Clinical Trials in Oncology independent Data and Safety Monitoring Board”.
Note:  ‘Unblinded’ means that those receiving the placebo will now be able to be administered the actual trial drug.  

What happens next?  

All will become clear, but the trial sponsor will meet with FDA to discuss the data. One seasoned clinical trial source suggested these discussions may take up to a year i this type of scenario.  I’ll keep you posted.

Read more here.

What is Cabozantinib?

Cabozantinib is an oral drug which works by blocking the growth of new blood vessels that feed a tumour. In addition to blocking the formation of new blood cells in tumours, Cabozantinib also blocks pathways that may be responsible for allowing cancers cells to become resistant to other “anti-angiogenic” drugs. It is a type of drug called a growth blocker.  Cabozantinib has been studied or is already in research studies as a possible treatment for various types of cancer, including prostate cancer, ovarian cancer, brain cancer, thyroid cancer, lung cancer, and kidney cancer.

Growth blockers are a type of targeted therapy and include tyrosine kinase inhibitors, proteasome inhibitors, mTOR inhibitors, PI3K inhibitors, histone deacetylase inhibitors and hedgehog pathway blockers.  Cabozantinib is a tyrosine kinase inhibitor (TKI).  They block chemical messengers (enzymes) called tyrosine kinases.  Tyrosine kinases help to send growth signals in cells so blocking them stop the cell growing and dividing.  Some TKIs can block more than one tyrosine kinase and these are known as multi-TKIs.

Example action of Cabozantinib

So Capozantinib is a targeted therapy and growth blocker just like Everolimus (Afinitor) and Sunitinib (Sutent). Very technical process but in the simplest of terms, Cabozantinib is designed to disrupt the actions of VEGF (a growth factor) and MET (a growth factor receptor) which promote spread of cancerous cells through the growth of new blood vessels.  Whilst we are on this subject, please note Everolimus (Afinitor) is an mTOR inhibitor and Sunitinib (Sutent) is a tyrosine kinase inhibitor. Many people think these drugs are a type of chemo – that is incorrect, these are targeted therapies.  See more on this by clicking here.

During my research, I found that it is an existing drug approval for other cancers and even has a connection to a type of Neuroendocrine Cancer called Medullary Thyroid Cancer (MTC). Cabozantinib, under the brand name of ‘Cometriq’ was approved by the FDA in 2012 for use in MTC which is frequently associated with Multiple Endocrine Neoplasia 2 (MEN2).   Read more about Cometriq here.  It’s also been approved by the FDA for advanced renal cell carcinoma (RCC) (branded as Cabometyx).

I also discovered that there is an exclusive licensing Agreement with the manufacturers (Elelixis) and Ipsen (of Lanreotide fame) to commercialize and develop Cabozantinib in regions outside the United States, Canada and Japan

The current trial status of Cabozantinib?

The now suspended Phase III trial is entitled “Randomized, Double-Blinded Phase III Study of Cabozantinib Versus Placebo in Patients With Advanced Neuroendocrine Tumors After Progression on Prior Therapy (CABINET)”. 

Sponsored by US’s National Institute of Health, the trial has around 435 locations across the US (see link below). The primary study (final data) was originally scheduled to complete Oct 2025 (but see breaking news above).

You can read the Phase 3 trial documentation by clicking hereThis contains the eligibility criteria via the inclusion and exclusion criteria and the trial locations amongst many other things. 

Are there other clinical trials of Cabozantinib for Neuroendocrine Neoplasms?

Yes, and they will have different sponsors and trial locations.  Continue reading below. 

There’s also another trial looking at unresectable metastatic Pheochromocytomas and Paragangliomas

A Phase 2 Study to Evaluate the Effects of Cabozantinib in Patients with Unresectable Metastatic Pheochromocytomas and Paragangliomas (only at MD Anderson Cancer Center Houston)

This part is from an article collaboration between MedPage Today® and the American Association of Clinical Endocrinologists

BOSTON — Cabozantinib (Cabometyx) may benefit patients with malignant pheochromocytomas and paragangliomas, according to results of a phase II trial presented here.

Patients receiving cabozantinib (Cometriq) treatment experienced notable tumor shrinkage in the lymph nodes, liver, and lung metastases, according to Camilo Jimenez, MD, of the MD Anderson Cancer Center in Houston, and colleagues.

Additionally, progression-free survival significantly increased after treated to 12.1 months (range 0.9-28) compared with just 3.2 months prior to treatment, they reported at the American Association of Clinical Endocrinologists (AACE) annual meeting.

Cabozantinib treatment was also tied to an improvement in blood pressure and performance status, as well as remission of diabetes among these patients.

“Malignant pheochromocytomas and paragangliomas are frequently characterized by an excessive secretion of catecholamines. [Patients] have a large tumor burden and they have a decreased overall survival,” explained Jimenez. “Tumors are frequently very vascular and frequently associated with bone metastases. In fact, up to 20% of patients who have malignancy of pheochromocytomas and paragangliomas may have predominant bone metastases.”

He added that “an interesting aspect of this tumor is that C-MET receptor mutation have been found in occasional patients with malignant pheochromocytomas and paragangliomas.”

Cabozantinib is an anti-angiogenic tyrosine kinase inhibitor, which also targets RET, MET, and AXL. It is approved for metastatic medullary thyroid cancer and was more recently approved for first-line treatment of advanced renal cell carcinoma.

“MET pathway is also involved in the development of bone metastases. In fact, cabozantinib is a very effective medications for patients who have bone metastases in the context of cancer of different origins,” Jimenez said.

In order to be eligible for the trial, patients with confirmed pheochromocytoma or paraganglioma had to be ineligible for curative surgery, have ≥3 months life expectancy, no risk for perforation or fistula, and adequate organ functioning. Prior to cabozantinib initiation, patients could not receive chemotherapy or biologic agents within 6 weeks, radiation within 4 weeks, or MIBG within 6 months.

Following histological confirmation of disease progression >1 year according to RECIST 1.1, the trial included 14 patients with measurable disease and eight patients with predominant/exclusive bone metastases. Fifteen patients subsequently enrolled into the trial, six of whom had germline mutations of the SDHB gene.

All participants were all started at an initial daily dose of 60 mg of cabozantinib, which was subsequently reduced down to between 40 to 20 mg due to toxicity in 13 patients based on tolerance.

The majority of these patients with measurable disease experienced some level of disease response. Six patients reported a partial response, defined as over a 30% reduction, while three patients achieved moderate response, marked by a 15%-30% reduction. Five of the patients with predominant bone metastases reported disease stabilization, according to results of an FDG-PET scan. One patient experienced disease progression while on treatment.

Overall, cabozantinib was generally well-tolerated without any grade 4 or 5 treatment-related adverse events reported. Some of the most common adverse events reported included grade mild dysgeusia, hand and foot syndrome, mucositis, fatigue, weight loss, and hypertension, according to the authors.

  • Primary Source – American Association of Clinical Endocrinologists meeting – AACE 2018; Abstract 142. attended my Medscape writers

What about Neuroendocrine Carcinoma? 

High-grade NENs are typically treated with platinum doublet chemotherapy; however, recurrences are inevitable and survival outcomes for patients with metastatic disease are dismal, underscoring the need for effective salvage treatment options. An ongoing hypothesis-generating phase 2 study (NCT04412629) is evaluating the efficacy and safety of the multitarget tyrosine kinase inhibitor cabozantinib in patients with high-grade NENs; the study design of this trial was presented at the 2020 North American Neuroendocrine Tumor Society Annual Symposium.  This trial is based in Washington University School of Medicine Missouiri. 

The eligibility criteria of the trial include patients with histologically confirmed high-grade, poorly differentiated NENs, excluding small-cell lung cancer, whose disease has progressed on first-line therapy; Eastern Cooperative Oncology Group performance status of 0 to 1; and Ki67 of ≥20% or mitotic count of >20 mitoses/high power field. Patients with transformed NENs, NENs of unknown origin, and mixed NENs were also eligible if a high-grade component is established. Eligible patients will receive oral cabozantinib at 60 mg daily on days 1 to 21 of a 21-day cycle.

The primary study end point is overall response rate; the secondary end points are safety, overall survival, and progression-free survival. Correlative studies for genetic and proteomic analysis will be performed using biopsy tissue acquired prior to cycle 2, as well as circulating tumor DNA from peripheral blood samples on day 1 of each cycle and on day 15 of cycle 1. Genetic analysis includes assessment of standard tumor markers, such as chromogranin, serotonin, urine 5-hydroxyindoleacetic acid, and specific hormones, dependent on the patient and investigator discretion. Whole-exome sequencing with copy number variant estimates of the initial biopsy (or optional start of treatment biopsy) will be performed.

See clinical trial document by clicking here. A small trial due to complete 31st July 2025.

Cabozantinib in High Grade Neuroendocrine Neoplasms – Full Text View –

Combo Trials

There is also another interesting trial involving Cabozantinib as a combo with Atezolizumab (Tecentriq).  Atezolizumab is an immunotherapy or more specifically a monoclonal antibody and a type of immune checkpoint inhibitor.  This trial is based in Spain and is due to complete Mar 2024.
The trial entitled: Exploratory Basket Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. CABATEN Study includes:

1. Well-differentiated neuroendocrine tumours of the lung and thymus (WHO grade 1 and 2, typical and atypical Lung NETs) after progression to somatostatin analogs, targeted agents, PRRT, and/or chemotherapy.

2. Pheochromocytoma and paraganglioma after progression to peptide receptor radionuclide therapy (PRRT) if indicated. Prior chemotherapy and biological therapy, such as somatostatin analogs, are allowed.

3. Well-differentiated neuroendocrine tumours of digestive system (WHO grade 1 and 2) after progression to somatostatin analogs, targeted agents, PRRT, and/or chemotherapy.

4. 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.

The clinical trial document can be found by clicking below:

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

Misc Clinical Trials involving Cabozantinib for Neuroendocrine Neoplasms

Other trials listed in Clinical Trials dot Gov with Cabozantinib for various types of Neuroendocrine Neoplasm include (and apologies for the out-of-date term ‘carcinoid’ and the sometimes-inadequate search engine of the clinical trials database):

Click here but please note the Clinical Trials database is notoriously out of date (behind in changing things) and the filtering (tailored search) is notoriously inefficient”


I generated this blog article to add value rather than just post the outputs for your own perusal.  I hope you find it useful.

General Clinical Trials Disclaimer

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact.  If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net

The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan. 



I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. 

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.   

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

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One thought on “Phase 3 CABINET Clinical Trial – Cabozantinib for Advanced Neuroendocrine Tumours

  • Diane mazejka

    Thank you Ronny for sharing this. Dr Chan is my sons oncologist (wonderful) in Boston, but I was not aware of this trial. He is currently back on CAPTEM after 30 months of stability, but we are always looking ahead for the next new drug/treatment coming up. Thanks again for your wonderful blog!

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