The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.

Whether 18F-ALF-NOTA-PRGD2 PET/CT Scan Can Predict the Efficacy and Adverse Events of Apatinib in Patients With Malignancies.

This is an open-label, single arm study to explore whether 18F-ALF-NOTA-PRGD2 PET/CT scan can predict the efficacy and adverse events of apatinib in patients with malignancies.

Integrin αvβ3 has been shown to play an important role in angiogenesis and up-regulated obviously in various types of tumor cells and activated endothelial cells. The arginine-glycine-aspartic acid (RGD) tripeptide sequence can bind to integrin αvβ3 with high affinity and specificity. The 18F-ALF-NOTA-PRGD2 will highly combine with αvβ3, and thus will monitor the antiangiogenic status.In the current study, investigators propose to evaluate the feasibility of 18F-RGD PET/CT in monitoring efficacy and adverse events of apatinib in malignancies.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Stomach Cancer; Breast Cancer; Esophageal Cancer; Non-small Cell Lung Cancer; Ovary Cancer; Malignancies
• Intervention / Treatment: Drug: Apatinib

Detailed Description

This is an open-label, single arm study to explore whether 18F-ALF-NOTA-PRGD2 positron emission tomography/computed tomography (18F-RGD PET/CT) scan can predict the efficacy and adverse events of apatinib in patients with malignancies.

Angiogenesis, the formation of new blood vessels, is the process of generating neovascularization from preexisting vessels. It can promote tumor growth and metastasis by providing nutrients and oxygen. Integrin αvβ3 has been shown to play an important role in angiogenesis and up-regulated obviously in various types of tumor cells and activated endothelial cells. Since the arginine-glycine-aspartic acid (RGD) tripeptide sequence can bind to integrin αvβ3 with high affinity and specificity, RGD PET/CT may be helpful to evaluate the biological and metabolic activity status during angiogenesis. However, 18F-ALF-NOTA-PRGD2 PET/CT as response biomarker for antiangiogenic therapy has not been fully proved and is still without universal understanding according to current publications. Apatinib (YN968D1) is the first orally antiangiogenic drug targeting VEGFR-2 tyrosine kinase.In the current study, investigators propose to evaluate the feasibility of 18F-RGD PET/CT in monitoring efficacy and adverse events of apatinib in malignancies. Patients confirmed malignancies histopathologically will be prospectively enrolled in the study. All patients provided written informed consent prior to enrollment. Patients will receive apatinib therapy, and undergo 18F-RGD PET/CT scans berore and after first cycle of therapy.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of malignancies
• Scheduled for second- or third-line apatinib therapy
• Karnofsky performance status (KPS) ≥70
• Measurable primary tumors according to Response Evaluation Criteria in Solid Tumors (RECIST)

Exclusion Criteria:

• Active infection, myocardial infarction within 6 months, symptoms of heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmias, immunosuppressive therapy
• The claustrophobic patients and patients with implanted metal objects
• The pregnancy
• Inability to complete the required examinations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Apatinib & RGD PET/CT; All of the patients will receive apatinib at oral dose of 250 mg twice daily (500 mg/day) at least 30 days.One treatment cycle is defined as 4 weeks.18F-ALF-NOTA-PRGD2 PET/CT scan will be performed berore and after one cycle of therapy. Treatment interruptions or dose reductions to 250 mg/day will be allowed for the management of adverse events. The maximum allowable period of treatment interruption is 1 week during each treatment cycle, and the dose should be re-escalated to 500 mg/day after adverse events mitigation. Treatment will not stop until disease progression, intolerable toxicity, or patients' request for withdrawal from the study.

Drug: Apatinib; Patients will accept apatinib therapy and undergo baseline 18F-ALF-NOTA-PRGD2 PET/CT scans of the whole body after having met all eligibility criterias.; Other Names: YN968D1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response defined by RECIST criteria	Tumor response will be evaluated as complete response or partial response or stable disease or PD according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.	At 1 month of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days from the start of therapy to disease progression or death due to any cause	Progression free survival (evaluated by RECIST criteria), defined as the interval from start of therapy to investigator-assessed progression or death due to any cause, whichever occurs first or lost of follow-up.	At 6 months of the study
Days from the start of therapy to death due to any cause	Overall survival is the time interval from the start of therapy to death due to any reason or lost of follow-up.	Up to 12 months
Treatment-Related Adverse Events as Assessed by CTCAE	Common Terminology Criteria for Adverse Events （CTCAE）	Through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute
• Investigators: Principal Investigator: Shuanghu Yuan, MD;PhD, Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2016
• Primary Completion (Actual): January 28, 2018
• Study Completion (Actual): January 28, 2018

Study Registration Dates

• First Submitted: September 1, 2017
• First Submitted That Met QC Criteria: December 26, 2017
• First Posted (Actual): December 27, 2017

Study Record Updates

• Last Update Posted (Actual): February 20, 2018
• Last Update Submitted That Met QC Criteria: February 19, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Apatinib; RGD PET-CT
• Additional Relevant MeSH Terms: Digestive System Diseases; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Neoplasms; Stomach Neoplasms; Ovarian Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: CRTOG1701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No