Neoplasms

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Thyroid Neoplasms

Thyroid Diseases

Neuroendocrine Tumors

Pheochromocytoma

Paraganglioma

Endocrine Gland Neoplasms

Thyroid Carcinoma, Anaplastic

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Paragangliomas 1

Anaplastic Thyroid Cancer

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

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

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).

Cabozantinib 40 mg

Jaume Capdevila, M.D, Ph.D

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.

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.

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

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

To assess the efficacy of cabozantinib plus atezolizumab combination by means of radiological objective response rate (ORR) in advanced endocrine tumors. Includes patients with confirmed partial (PR) and complete response (CR) as best response according to RECIST v 1.1.

Number of serious adverse events classified by severity as assessed by CTCAE v4.0

Number of serious adverse events related to the investigational drug classified by severity as assessed by CTCAE v4.0

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).

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.

Median Overall Survival (mOS) is calculated as the time from date of inclusion to date of death due to any cause.

Ipsen

Roche Pharma AG

Grupo Espanol de Tumores Neuroendocrinos

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Cabozantinib will be administered orally at a (starting) dose of 60 mg once daily. The drug is taken continuously over a period of 28 days (4 weeks), which constitutes one treatment cycle. In all subjects, dose reductions and delays to manage toxicity. Cabozantinib should be taken in fasting condition with no food for at least 2 hours before and 1 hour after taking the tablets. A high fat meal significantly increased the median tmax to 6 hours from 4 hours (fasted). The treatment will be continued until disease progression, intolerable toxicity, patient refusal or Investigator's decision or any criterion for withdrawal from the trial or trial drug is fulfilled.

Cabozantinib will be administered orally at a (starting) dose of 60 mg once daily. The drug is taken continuously over a period of 28 days (4 weeks), which constitutes one treatment cycle. In all subjects, dose reductions (40mg 20mg) and delays to manage toxicity.

Cabozantinib 20 MG

Cabozantinib 40 MG

Cabozantinib 60 MG

Andrea Ardizzoni, MD

Giada Grilli, MD

Andrea Ardizzoni, DM

Francesco Gelsomino, DM

Karim Rihawi, DM

Hector Soto Parra, DM

Carlo Genova, DN

Carlo Genova, DM

Marina Chiara Garassino, DM

Linda Pallavicini

Marina Chiara Ganassino, DM

Danilo Rocco, DM

Giulia Pasello, DM

Raffaella Verrienti

Marcello Tiseo, DM

Roberta Camisa

Fausto Roila, DM

Antonio Chella, DM

Sabrina Vari, DM

Sonia Borrelli

Ciro Rossetto, dm

Ciro Rossetto, DM

This study is aimed to explore the antitumor activity, safety and efficacy profile of cabozantinib in pretreated, advanced RET-rearranged non-small cell lung cancer patients

Phase II Study With Cabozantinib in Patients With RET Positive NSCLC

"Phase II Study to Evaluate the Activity and Safety of Cabozantinib in Pretreated, Advanced RET-rearranged Non-small Cell Lung Cancer Patients: CRETA Trial"

Detection of RET aberration on DNA extracted from circulating tumor cells (CTCs) isolated in blood at baseline (optional)

Archival tumor tissue (FFPE tumor block or 7-10 unstained slides) will be assessed for determination of RET-rearrangment on tumor cells by using A FISH evaluation of the translocation will be performed using a break-apart probe for the 10p11 locus.

Exact binomial method will be used to estimate the response rate (CR+PR) and its 95% confidence interval.Proportion of patients presenting Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) based on the Investigator's assessment according to standard RECIST criteria v1.1. Patients with no tumor assessment after baseline will be classified as non-responders.

the assessment of safety will be based mainly on the frequency of adverse events; toxicity will be measured according to NCI Common Toxicity Criteria Adverse Event (CTCAE), version 4.03.

PFS will be calculated from the first treatment intake to the date of progressive disease, or death.

OS will be calculated from the first treatment intake to death from any cause.

DOR will be calculated from the first treatment intake to the date of disease progression or death.

DCR will be measured as the sum of complete and partial responses + stable disease.

AOU S.Orsola Malpighi-Unit of Oncologic Molecular and Transplantations Pathology

Bioikos Ambiente Srl

Mipharm SpA

University of Bologna

Professor/MD

Symptoms and General Pathology

Digestive System Diseases

Neoplasm Metastasis

Carcinoma, Squamous Cell

Esophageal Neoplasms

Recurrence

Esophageal Squamous Cell Carcinoma

Neoplasms, Squamous Cell

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

cabozantinib 40mg PO QD atezolizumab 1200mg IVD 30-60mins Q3W

atezolizumab (Tecentriq) 1200mg IVF 30-60mins Q3W

Atezolizumab Injection

Hung-Yang Kuo, M.D.

Min-Yi Cheng

Daniel Fu-Chang Tsai, M.D.,Ph.D.

Chih-Hung Hsu, M.D.,Ph.D.

Ta-Chen Huang, M.D.

Jhe-Cyuan Guo, M.D.

Chia-Chi Lin, M.D.,Ph.D.

Kun-Huei Yeh, M.D.,Ph.D.

Jang-Ming Lee, M.D.,Ph.D.

Pei-Ming Huang, M.D.,Ph.D.

To demonstrate that combination of cabozantinib and atezolizumab is safe and efficacious in patients with recurrent/metastatic esophageal squamous cell carcinoma.

Patients with histologically proven squamous cell carcinoma of esophagus and had progression from first-line platinum-based chemotherapy for recurrent or metastatic ESCC, or progression within 6 months after neoadjuvant, definitive, or adjuvant chemo(radio) -therapy for loco-regional ESCC would be eligible for this trial. Eligible patients will receive daily 40mg cabozantinib plus i.v. atezolizumab 1200mg Q3W for treatment response evaluation. Primary endpoint is the objective response rate, and secondary endpoints include progression-free survival, overall survival, and safety profiles.

Second-line Cabozantinib and Atezolizumab in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

A Single-arm Phase II Study of Cabozantinib and Atezolizumab in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma Who Failed a Platinum-based Chemotherapy

Overall response rate (ORR) is the proportion of patients whose tumor is significantly reduced.

Progression-free survival (PFS) is the time from enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) and will be conducted in the whole study population. It is designed to include progression events as determined by the investigators per RECIST 1.1 or death.

Overall survival (OS) is the time from enrollment to death of any cause or the last follow-up (censored).

The incidence and severity of toxicity will be summarized according to the NCI Common Toxicity Criteria Version 4.0.

National Taiwan University Hospital

Pembrolizumab

All subjects will receive carbozantinib 40mg PO once daily Days 1-21 Q3W and pembrolizumab 200mg IV infusion Q3W or 400mg IV infusion Q6W per the treating physician's discretion as maintenance therapy following 4 cycles of induction therapy with disease control

Note: Cabozantinib should be stopped at least 3 weeks prior to elective surgery. Do not administer cabozantinib for at least 2 weeks after major surgery and until complete wound healing.

Pembrolizumab 200mg

Pembrolizumab 400mg

Ryan Nguyen, DO

Arielle Guzman, MPH

This is a phase II study to assess the efficacy, safety, and Health Related Quality of Life (HRQoL) of combination cabozantinib and pembrolizumab as maintenance therapy for patients with metastatic squamous Non Small Cell Lung Cancer(sqNSCLC) who have received 4 cycles of induction therapy with pembrolizumab, carboplatin, and nab-paclitaxel or paclitaxel

This is a phase II study to assess the efficacy, safety, and Health Related Quality of Life (HRQoL) of combination cabozantinib and pembrolizumab as maintenance therapy for patients with metastatic sqNSCLC who have received 4 cycles of induction therapy with pembrolizumab, carboplatin, and nab-paclitaxel or paclitaxel and achieved disease control following induction therapy defined as complete response, partial response, or stable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 criteria. Subjects with disease control would proceed to maintenance therapy with pembrolizumab and cabozantinib.

A Pilot Phase II Study of Maintenance Cabozantinib Plus Pembrolizumab for Patients With Metastatic Squamous Non-Small Cell Lung Cancer (sqNSCLC)

LUNG-IST-127: A Pilot Phase II Study of Maintenance Cabozantinib Plus Pembrolizumab (CP) for Patients With Metastatic sqNSCLC With Disease Control Following Induction Therapy

PFS is defined as the time from initiation of induction treatment until the criteria for disease progression is met as defined by irRECIST1.1 or death as a result of any cause for patients with disease control (defined as complete response (CR), partial response (PR), or stable disease) following induction therapy who proceed to maintenance therapy with cabozantinib in combination with pembrolizumab

Number of subjects achieving ORR using RECIST v1.1 with disease control following standard first-line induction therapy who received cabozantinib in combination with pembrolizumab as maintenance thherapy

Number of subjects having a high score, which means a poorer quality of life

Number of subjects having a low score, which means a better quality of life

University of Illinois at Chicago

Principal Investigator

Amino Acids

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Erlotinib 100Mg Tab

Bert H. O'Neil, MD

This is an open-label, single arm, phase II trial. Safety will be monitored on an ongoing basis. Laboratory testing (chemistry, hematology tests) will be performed every 2 weeks for the first 8 weeks followed by assessments every 4 weeks. Other safety evaluations including EKGs, urinalysis, coagulation and thyroid function studies will be performed at regular intervals.

Adverse event seriousness, severity grade, and relationship to study treatment will be assessed by the investigator. Severity grade will be defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Tumors will be assessed by contrast enhanced CT or MRI every 8 weeks. Pre-treatment tissue will be obtained via CT-guided FNA biopsy or collected during resection. However, archival tissue will also be requested, when available and if adequate for testing. Post-treatment tissue will be obtained on Day 15 (i.e., Week 3/Day 1) via CT-guided FNA biopsy. All tumor tissue from eligible patients will be utilized for the correlative studies which are outlined in this trial.

Each subject's course will consist of three periods:

* A Pre-Treatment Period in which subjects are consented and undergo screening assessments to be qualified for the study;
* A Treatment Period in which subjects receive study treatment and undergo study assessments. Patients who meet the eligibility criteria will be treated with cabozantinib orally at 40 mg daily and erlotinib orally at 100 mg daily without breaks;
* A Post-Treatment Period in which subjects no longer receive study treatment but undergo follow-up study assessments and contacts.

Primary Objective The primary objective of this trial is to demonstrate a radiographic response rate of 15% or greater for the combination in a selected population.

Secondary Objectives

The secondary objectives of this trial are:

* To estimate progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), overall survival (OS); and
* To assess safety and tolerability of this combination in the target patient population.

Correlative Objectives

The following tests will be performed on blood and tumor tissue samples collected during this trial to correlate with PFS and OS:

* c-Met and EGFR mRNA by RT-qPCR
* plasma HGF and soluble Met receptor
* c-Met and EGFR phosphoprotein levels by IHC
* KRAS mutation status

Cabozantinib and Erlotinib for Patients With EGFR and c-Met Co-expressing Metastatic Pancreatic Adenocarcinoma

A Phase II Trial of Cabozantinib and Erlotinib for Patients With EGFR and c-Met Co-expressing Metastatic Pancreatic Adenocarcinoma

Percent of patients with Objective response and the Binomial Exact 95% confidence interval. Objective response is defined as having a best response of Complete Response (defined as disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10mm) or Partial Response (defined as at least a 30% decrease in the sum of diameters of target lesions from the baseline sum diameters) by RECIST v1.1 criteria.

Percent of patients achieving disease control and the Binomial Exact 95% confidence interval. Disease control is defined as having a best response of Complete Response (defined as disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10mm) or Partial Response (defined as at least a 30% decrease in the sum of diameters of target lesions from the baseline sum diameters) or Stable Disease for at least 4 months (defined by neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression) by RECIST v1.1 criteria.

Duration of time from the start of treatment to time of documented progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients who do not progress or die will be censored on their last evaluation date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.

Duration of time from the start of treatment to time of death due to any causes. Patients who do not die will be censored on their last known alive date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.

Number of unique patients who had a treatment related (possible, probable or definite) adverse events with grade \>= 3.

Exelixis

Patrick Joseph Loehrer Sr.

Associate Dean for Cancer Research Director, Indiana University Melvin and Bren Simon Cancer Center

Cabozantinib 40 MG: To be taken orally once daily

Erlotinib 100Mg Tab: To be taken orally once daily

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. The CABATEN Study	NCT04400474	Neuroendocrine ... Anaplastic Thyr... Adenocarcinoma Pheochromocytom... Paraganglioma	Cabozantinib 40...	18 Years -	Grupo Espanol de Tumores Neuroendocrinos
Phase II Study With Cabozantinib in Patients With RET Positive NSCLC	NCT04131543	Non Small Cell ...	Cabozantinib 20... Cabozantinib 40... Cabozantinib 60...	18 Years -	University of Bologna
Second-line Cabozantinib and Atezolizumab in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma	NCT05007613	Esophageal Canc... Metastatic Canc... Squamous Cell C...	Cabozantinib 40... Atezolizumab In...	20 Years -	National Taiwan University Hospital
A Pilot Phase II Study of Maintenance Cabozantinib Plus Pembrolizumab for Patients With Metastatic Squamous Non-Small Cell Lung Cancer (sqNSCLC)	NCT05613413	Metastatic Squa...	Cabozantinib 40... Pembrolizumab 2... Pembrolizumab 4...	18 Years -	University of Illinois at Chicago
Phase II Study With Cabozantinib in Patients With RET Positive NSCLC	NCT04131543	Non Small Cell ...	Cabozantinib 20... Cabozantinib 40... Cabozantinib 60...	18 Years -	University of Bologna
Second-line Cabozantinib and Atezolizumab in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma	NCT05007613	Esophageal Canc... Metastatic Canc... Squamous Cell C...	Cabozantinib 40... Atezolizumab In...	20 Years -	National Taiwan University Hospital
Cabozantinib and Erlotinib for Patients With EGFR and c-Met Co-expressing Metastatic Pancreatic Adenocarcinoma	NCT03213626	Pancreatic Aden...	Cabozantinib 40... Erlotinib 100Mg...	18 Years -	Indiana University
A Pilot Phase II Study of Maintenance Cabozantinib Plus Pembrolizumab for Patients With Metastatic Squamous Non-Small Cell Lung Cancer (sqNSCLC)	NCT05613413	Metastatic Squa...	Cabozantinib 40... Pembrolizumab 2... Pembrolizumab 4...	18 Years -	University of Illinois at Chicago

Spots Global Cancer Trial Database for cabozantinib 40 mg