Study of Apatinib in RET Fusion Positive Advanced Non-small Cell Lung Cancer

A Phase II Clinical Trial to Investigate Efficacy and Safety of Apatinib as a Single Agent in RET-fusion Gene Positive Non-small Cell Lung Cancer Who Failed to Previous Treatment.

RET fusions are present in 1% to 2% of unselected population of non-small cell lung cancer (NSCLC). Existing US Food and Drug Administration-approved inhibitors of RET tyrosine kinase show promising therapeutic effects in a non-small cell lung cancer patients. Apatinib is an oral multi-kinase inhibitors including RET fusions. This study is designed to evaluate the safety and tolerability of Apatinib in patients with RET fusion positive advanced NSCLC.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Apatinib single agent arm

Detailed Description

To observe objective response rate (ORR) of apatinib in RET fusion positive pre-treated advanced NSCLC.

To observe Progression free survival （PFS）. To assess the overall survival (OS). To assess safety and tolerability. To evaluate quality of life. To explore the relationship between biomarkers and the toxicity/efficacy of apatinib.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200433
    • Recruiting
    • Department of Oncology, Shanghai pulmonary hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged ≥18 and ≤80 years.
• ECOG performance status of 0 to 1.
• Life expectancy of more than 12 weeks.
• At least one measurable lesion exists.(RECIST 1.1)
• Histologically or cytologic confirmed RET fusion positive advanced Non-small cell lung cancer who failed to prior therapies.
• Required laboratory values including following parameters: ANC: ≥ 1.5 x 10^9/L, Platelet count: ≥ 80 x 10^9/L, Hemoglobin: ≥ 90 g/L, Total bilirubin: ≤ 1.5 x upper limit of normal, ULN, ALT and AST: ≤ 1.5 x ULN, BUN and creatine clearance rate: ≥ 50 mL/min LVEF: ≥ 50% QTcF: < 470 ms
• Signed informed consent
• Females of child-bearing potential must have negative serum pregnancy test. Sexually active male and those having childbearing potential must practice contraception during the study.

Exclusion Criteria:

• Squamous carcinoma (including adeno-squamous carcinoma), small cell lung cancer
• Subjects with third space fluid that can not be controled by drainage or other methods.
• Obvious cavity or necrosis formed in the tumor
• Uncontrolled hypertension
• Hymoptysis, more than 2.5ml daily
• Thrombosis in 12 months, including pulmonary thrombosis, stroke, or deep venous thrombosis
• Received big surgery, had bone fracture or ulcer in 4 weeks
• Urine protein >++, or urine protein in 24 hours> 1.0g
• pregnant or lactating woman
• Receiving any other antitumor therapy.
• Known history of hypersensitivity to apatinib or any of it components.

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 single agent arm; Apatinib, single agent, 750mg once daily p.o until disease progression	Drug: Apatinib single agent arm; For RET-fusion positive advanced NSCLC patients who failed to previous treatment,treat with apatinib, single agent, 750mg once daily, p.o until disease progression; Other Names: YN968D1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	To evaluate ORR every 6-8 weeks after initiation of apatinib	change from baseline in tumor size every 6-8 weeks after the initiation of apatinib, up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is evaluated in 24 months since the treatment began	24 months
overall survival (OS)	evaluated in the 24th month since the treatment began	24 months
Safety and Tolerability as measured by adverse events	Number of Participants with treatment related Adverse Events as Assessed by CTCAE v4.0	24 months
quality of life (QOL, measured by questionnaire)	Change from baseline in Pain on the 11 point short pain scale (SPS-11)	24 months

Collaborators and Investigators

• Sponsor: Tongji University

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: August 29, 2015
• First Submitted That Met QC Criteria: September 3, 2015
• First Posted (Estimate): September 4, 2015

Study Record Updates

• Last Update Posted (Estimate): September 4, 2015
• Last Update Submitted That Met QC Criteria: September 3, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Apatinib; Non-small Cell Lung Cancer; RET; gene fusion
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: FK-1407