Randomized, Double-Blinded Phase III Study of CABozantinib Versus Placebo IN Patients With Advanced NEuroendocrine Tumors After Progression on Prior Therapy (CABINET)

Plain English Summary

Testing Cabozantinib in Patients With Advanced Pancreatic Neuroendocrine and Carcinoid Tumors is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Functioning Pancreatic Neuroendocrine Tumor, Intermediate Grade Lung Neuroendocrine Neoplasm, Locally Advanced Digestive System Neuroendocrine Neoplasm, Locally Advanced Digestive System Neuroendocrine Tumor G1, Locally Advanced Lung Neuroendocrine Neoplasm, Locally Advanced Pancreatic Neuroendocrine Tumor, Locally Advanced Unresectable Digestive System Neuroendocrine Neoplasm, Low Grade Lung Neuroendocrine Neoplasm, Lung Neuroendocrine Tumor, Lung Neuroendocrine Tumor G2. Tests cabozantinib, a targeted chemotherapy drug, to see if it works better than a placebo in treating advanced neuroendocrine or carcinoid tumors. For patients with advanced neuroendocrine or carcinoid tumors who have already tried other treatments. Participation involves taking cabozantinib or a placebo, regular check-ups, and imaging tests. Alternative treatments include other chemotherapy drugs, immunotherapy, and somatostatin analogs. The trial aims to enroll 298 participants.

Official Summary

This phase III trial studies cabozantinib to see how well it works compared with placebo in treating patients with neuroendocrine or carcinoid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Cabozantinib is a chemotherapy drug known as a tyrosine kinase inhibitor, and it targets specific tyrosine kinase receptors, that when blocked, may slow tumor growth.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if you have a well- or moderately-differentiated neuroendocrine tumor of pancreatic or non-pancreatic origin, with locally advanced or metastatic disease. Not eligible if you have poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, or specific types of neuroendocrine tumors. Age: 18+ years. Health: No significant heart or lung issues, no uncontrolled hypertension. This trial is studying Functioning Pancreatic Neuroendocrine Tumor, Intermediate Grade Lung Neuroendocrine Neoplasm, Locally Advanced Digestive System Neuroendocrine Neoplasm, Locally Advanced Digestive System Neuroendocrine Tumor G1, Locally Advanced Lung Neuroendocrine Neoplasm, Locally Advanced Pancreatic Neuroendocrine Tumor, Locally Advanced Unresectable Digestive System Neuroendocrine Neoplasm, Low Grade Lung Neuroendocrine Neoplasm, Lung Neuroendocrine Tumor, Lung Neuroendocrine Tumor G2, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the time until the tumor progresses, which is important for patients as it can help extend their quality of life. The specific primary outcome measures are: Progression-free Survival (PFS) (36 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial fills a gap by testing a new treatment for advanced neuroendocrine tumors that have progressed despite previous therapies. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Functioning Pancreatic Neuroendocrine Tumor, Intermediate Grade Lung Neuroendocrine Neoplasm, Locally Advanced Digestive System Neuroendocrine Neoplasm, Locally Advanced Digestive System Neuroendocrine Tumor G1, Locally Advanced Lung Neuroendocrine Neoplasm, Locally Advanced Pancreatic Neuroendocrine Tumor, Locally Advanced Unresectable Digestive System Neuroendocrine Neoplasm, Low Grade Lung Neuroendocrine Neoplasm, Lung Neuroendocrine Tumor, Lung Neuroendocrine Tumor G2, where improved treatment options are needed.

Investor Insight

The market size for neuroendocrine tumors is growing, with limited approved treatments, making this trial significant for investors. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have a neuroendocrine tumor that has progressed after previous treatments. Participation involves regular check-ups, blood tests, and imaging scans. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 298 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo blood and urine sample collection
• DRUG: Cabozantinib S-malate — Given PO
• PROCEDURE: Computed Tomography — Undergo CT
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI
• OTHER: Placebo Administration — Given PO

Primary Outcomes

• Progression-free Survival (PFS) (36 months)

Secondary Outcomes

• Overall Survival (OS) (60 months)
• Number of Patients Experiencing Grade 3+ Adverse Events (AEs) Graded According to the Common Terminology Criteria for Adverse Events (CTCAE) and Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) (60 months)
• Radiographic Response Rate (36 months)

Full Eligibility Criteria

Inclusion Criteria:

* Documentation of Disease:

  * Histologic Documentation: Well- or moderately-differentiated neuroendocrine tumors of pancreatic and non-pancreatic (i.e. carcinoid) origin by local pathology

    * The pathology report must state ONE of the following: 1) well- or moderately-differentiated neuroendocrine tumor, 2) low- or intermediate-grade neuroendocrine tumor, or 3) carcinoid tumor or atypical carcinoid tumor; documentation of histology from a primary or metastatic site is allowed
    * Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma without specification of differentiation status, adenocarcinoid tumor, or goblet cell carcinoid tumor are not eligible. Patients with well-differentiated grade 3 neuroendocrine tumor are eligible
  * Stage: Locally advanced/unresectable or metastatic disease
  * Tumor Site: Histological documentation of neuroendocrine tumor of pancreatic, gastrointestinal (GI), lung, thymus, other, or unknown primary site; GI, lung, thymus, other, and unknown primary NETs will enroll in the carcinoid tumor cohort of the study

    * Functional (i.e., associated with symptoms or clinical syndrome related to hormone secretion by tumor) or nonfunctional tumors are allowed
  * Radiologic Evaluation: Target lesions must have shown evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria in the 12 months prior to registration; the radiologic images, imaging reports, and clinic notes indicating growth of existing lesions, development of new lesions, or treatment changes must be submitted
* Measurable Disease

  * Patients must have measurable disease per RECIST 1.1 by computer tomography (CT) scan or magnetic resonance imaging (MRI)
  * Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 1 cm with CT or MRI (or \>= 1.5 cm for lymph nodes); non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung
* Prior Treatment

  * Patient must have experienced disease progression after receiving or intolerance leading to treatment discontinuation of at least one Food and Drug Administration (FDA)-approved line of therapy (except somatostatin analogs); prior lines of therapy must include one of the following: everolimus, sunitinib, or lutetium Lu 177 dotatate in patients with pancreatic NET; everolimus in patients with lung NET; everolimus or lutetium Lu 177 dotatate in patients with gastrointestinal NET
  * Prior treatment (except somatostatin analogs) with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, and/or radiation must be completed at least 28 days prior to registration
  * Prior treatment with somatostatin analogs is allowed, and continuation of treatment with somatostatin analogs while on cabozantinib/placebo is allowed provided that the patient has been on a stable dose for at least two months
  * Prior systemic treatment with radionuclide therapy must be completed at least 6 weeks prior to registration
  * Prior treatment with hepatic artery embolization (including bland embolization, chemoembolization, and selective internal radiation therapy) or ablative therapies is allowed if measurable disease remains outside of the treated area or if there is documented disease progression in a treated site; prior liver-directed or other ablative treatment must be completed at least 28 days prior to registration
  * Prior treatment with cabozantinib is not allowed
  * Patients should have resolution of any toxic effects of prior therapy (except alopecia and fatigue) to National Cancer Institute (NCI) CTCAE, version 5.0, grade 1 or less
  * Patients must have completed any major surgery at least 12 weeks prior to registration and any minor surgery (including uncomplicated tooth extractions) at least 28 days prior to registration; complete wound healing from major surgery must have occurred at least 28 days prior to registration, and complete wound healing from minor surgery must have occurred at least 10 days prior to registration
* Patient History

  * No class III or IV congestive heart failure (CHF) within 6 months of registration
  * No clinically significant cardiac arrhythmia within 6 months of registration
  * No unstable angina or myocardial infarction (MI) within 6 months of registration
  * No thromboembolic events within 6 months of registration (including \[incl.\] stroke, transient ischemic attack \[TIA\], deep vein thrombosis \[DVT\], \& pulmonary embolism \[PE\])
  * No known history of congenital long QT syndrome
  * No uncontrolled hypertension within 14 days of registration (defined as systolic blood pressure \[SBP\] \>= 150 mmHg and/or diastolic blood pressure \[DBP\] \>= 90 mmHg despite optimal medical managemen

Trial Locations

• Katmai Oncology Group, Anchorage, Alaska, United States
• Kingman Regional Medical Center, Kingman, Arizona, United States
• Mayo Clinic Hospital in Arizona, Phoenix, Arizona, United States
• Banner University Medical Center - Tucson, Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus, Tucson, Arizona, United States
• University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
• Kaiser Permanente-Deer Valley Medical Center, Antioch, California, United States
• PCR Oncology, Arroyo Grande, California, United States
• Sutter Auburn Faith Hospital, Auburn, California, United States
• Alta Bates Summit Medical Center-Herrick Campus, Berkeley, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Functioning Pancreatic Neuroendocrine Tumor
• Intermediate Grade Lung Neuroendocrine Neoplasm
• Locally Advanced Digestive System Neuroendocrine Neoplasm
• Locally Advanced Pancreatic Neuroendocrine Tumor
• Low Grade Lung Neuroendocrine Neoplasm
• Lung Neuroendocrine Tumor

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