Cabozantinib in High Grade Neuroendocrine Neoplasms

NCT04412629 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202007173
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

High grade neuroendocrine neoplasm patients are treated with platinum doublets such as carboplatin and etoposide mimicking the current guidelines for small cell lung cancer (SCLC). Unfortunately, recurrences are common and most patients with metastatic disease succumb to it within a year. There is no extensive literature or consensus on second- or third-line options (which include FOLFOX, FOLFIRI, capecitabine and temozolomide, taxanes or immunotherapy) and there is urgent need for better regimens.

Conditions

High Grade Neuroendocrine Neoplasms

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  * ORR is defined as number of patients with complete response or partial response * Complete response - Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. * Partial response - At least a 30% decrease in the sum of the diameters of the longest diameter of the target lesions taking as reference the baseline sum longest diameter

  Through the end of treatment (estimated to be 4 months)

Secondary Outcomes (3)

• Overall survival (OS)

  Through completion of follow-up (estimated to be 1 year)

• Progression-free survival (PFS)

  Through completion of follow-up (estimated to be 1 year)

• Safety of regimen as measured by incidence of adverse events

  From start of treatment through 30 days after last dose of study treatment (estimated to be 5 months)

Study Arms (1)

Cabozantinib

EXPERIMENTAL

-Cabozantinib 60 mg by mouth daily on days 1-21

Drug: Cabozantinib; Procedure: Blood for plasma biomarkers; Procedure: Tissue biopsy

Interventions

Cabozantinib DRUG

Cabozantinib should be taken on an empty stomach (at least 1 hour before or 2 hours after eating) at the same time every day.

Also known as: Cabometyx

Cabozantinib

Blood for plasma biomarkers PROCEDURE

Baseline, cycle 1 day 8, cycle 1 day 15, and day 1 of every cycle thereafter

Cabozantinib

Tissue biopsy PROCEDURE

Baseline, before start of cycle 2, and time of progression

Cabozantinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed high-grade neuroendocrine tumor that has progressed after at least one line of therapy, excluding small cell lung cancer (SCLC). High grade includes any neuroendocrine neoplasm with a Ki-67 of \>=20% or with mitotic count of more than 20 mitoses per high power field or any poorly differentiated neoplasm or any neoplasm lacking these that is deemed high grade by pathology consensus, based on other markers (necrosis or IHC demonstrating p53 or RB mutation). This includes:
• High grade well differentiated neuroendocrine neoplasms
• Transformed NENs from a lower to a higher grade (patient may have some low grade and some high grade NENs)
• High grade neoplasms with significant expression of neuroendocrine markers such as synaptophysin, chromogranin or INSM-1 or unknown origin neoplasms with gene expression signatures consistent with neuroendocrine lineage (as per validated tissue of origin testing, such as CancerType ID, after pathology consensus).
• Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNEN), including MiNEN per WHO and mixed neoplasms not fulfilling criteria of MiNEN. The neuroendocrine component would need to be a high-grade neuroendocrine tumor as documented by pathology review.
• Note: Up to two prostate NEC patients (primary diagnosis, not transformed adenocarcinoma) will be enrolled in the first phase. For the second phase, non gastroenteropancreatic or lung histologies will be approved by PI.
• Note: For ambiguous cases, will consult with a designated expert pathologist.
• Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
• Concurrent or prior somatostatin analogue therapy is allowed (for well differentiated high grade neoplasms). Prior use of investigational agents is allowed.
• At least 18 years of age.
• ECOG performance status ≤ 1 (Karnofsky ≥ 80%)
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500/mm3 without granulocyte colony-stimulating factor support
• White blood cell count ≥ 2,500/mm3
• Platelets ≥ 100,000/mm3 without transfusion

You may not qualify if:

• A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease. Allowed are superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy at any point in the prior year.
• Currently receiving any other investigational agents. Prior use of investigational agents is allowed.
• Prior treatment with cabozantinib.
• Receipt of any small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before the first dose of study treatment.
• Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before the first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Patients with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment.
• Inability to swallow tablets.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib or other agents used in the study.
• Concomitant anticoagulation with coumarin agents (e.g. warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g. clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH)
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Exelixis: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Abstracts Presented at the 13th Annual Multidisciplinary Neuroendocrine Tumor Medical Virtual Symposium of the North American Neuroendocrine Tumor Society, October 2-3, 2020. Pancreas. 2021 Mar 1;50(3):441-467. doi: 10.1097/MPA.0000000000001763. No abstract available.

  PMID: 33835977 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Interventions

cabozantinib; Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Nikolaos Trikalinos, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

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 28, 2020
• First Posted: June 2, 2020
• Study Start: November 24, 2020
• Primary Completion: March 31, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)