Sunitinib in Never-Smokers With Lung Adenocarcinoma

A Phase II Trial of Sunitinib in Never-smokers With Lung Adenocarcinoma: Identification of Oncogenic Alterations Underlying Sunitinib Sensitivity

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It also means that the FDA has not yet approved sunitinib for your type of cancer.

Sunitinib has been approved by the FDA for treatment of gastrointestinal stromal tumors, advanced renal cell carcinoma and advanced pancreatic neuroendocrine tumors. While most chemotherapies work by interfering with cancer cell replication, sunitinib works by blocking certain protein signals within the cell. Because sunitinib works differently from standard intravenous chemotherapies, we call it a "targeted therapy." This drug has also been used in other research studies and information from those other research studies suggests that this agent may help to slow the growth of some NSCLC tumors.

In this research study, we are looking to see if sunitinib may stop certain NSCLC tumors from growing. The study focuses on a type of NSCLC, adenocarcinoma, which has previously been found to be more sensitive to other kinds of oral targeted therapies. This study will focus specifically on (1) adenocarcinoma tumors that do not carry a mutation in a known cancer gene (EGFR, KRAS, or ALK) and occur in patients that never smoked (less than 100 cigarettes in their lifetime) or (2) adenocarcinoma tumors that have a mutation in the RET gene.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Sunitinib

Detailed Description

Primary Objectives

- To evaluate the objective response rate (ORR) to sunitinib in never-smokers with lung cancers that are wild-type for EGFR, KRAS, and ALK in a single-arm phase II trial

Secondary Objectives

• To identify oncogenic alterations underlying sensitivity to sunitinib through performing nextgeneration sequencing (NGS) of lung cancers treated with sunitinib
• To explore the activity of sunitinib in lung cancers known to harbor a RET rearrangements and other genomic alterations in targets of sunitinib (e.g. cKIT, PDGFRa, PDGFRb).

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02214
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Beth Isreal Deaconess Medical Center

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:

• Histologically or cytologically confirmed advanced (stage IV or recurrent) non-small cell lung cancer
• Adenocarcinoma histology of any variant, including adenosquamous histology
• Wild-type for mutations in EGFR, KRAS and ALK
• Must have < 100 cigarettes smoked lifetime OR known to harbor a RET rearrangement OR another potentially targetable genomic alteration as defined per protocol
• Disease must be measureable per RECIST 1.1
• At least one prior systemic therapy (adjuvant or palliative)
• 18 years or older
• Life expectancy of greater than 4 weeks
• Adequate ECOG performance status 0 or 1
• Adequate organ function as defined in the protocol
• Adequate tumor tissue for the correlative analyses on study, or must undergo a biopsy to obtain adequate tissue

Exclusion Criteria:

• Pregnant or breastfeeding
• Chemotherapy within 4 weeks of entering study, or lack of recover from adverse events to grade 1 or less due to systemic agents administered more than 4 weeks earlier
• Radiation therapy within 2 weeks prior to entering study
• Major surgery within 4 weeks prior to entering the study
• Receiving any other investigational agents
• Known untreated, symptomatic or progressive brain metastases; presence of carcinomatous meningitis; history of intracranial hemorrhage or brain metastases requiring chronic steroids
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib
• Use of certain inhibitors and inducers of CYP3A4
• Grade 3 or 4 hemoptysis or hemorrhage within 4 weeks prior to study entry
• History of significant bleeding disorder unrelated to cancer
• Poorly controlled hypertension
• Severe cardiovascular disease
• Prolongation of corrected QT interval
• History of a different malignancy except: cervical cancer in situ, basal or squamous cell carcinoma of the skin, low risk centralized prostate cancer
• HIV positive on combination antiretroviral therapy

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: Sunitinib; 42 day cycle, taken orally every day for the first 28 days followed by 14 days off	Drug: Sunitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Percentage of patients with evidence of complete or partial response per RECIST1.1 criteria.	ORR was assessed at 6 weeks post-registration and every 6 weeks until date of documented disease progression or death, up to January 23, 2017 (approximately 44 months).

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Geoffrey Oxnard, MD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Wu H, Shih JY, Yang JC. Rapid Response to Sunitinib in a Patient with Lung Adenocarcinoma Harboring KIF5B-RET Fusion Gene. J Thorac Oncol. 2015 Sep;10(9):e95-e96. doi: 10.1097/JTO.0000000000000611. No abstract available.
• Cooper AJ, Kobayashi Y, Kim D, Clifford SE, Kravets S, Dahlberg SE, Chambers ES, Li J, Rangachari D, Nguyen T, Costa DB, Rabin MS, Wagle N, Sholl LM, Janne PA, Oxnard GR. Identification of a RAS-activating TMEM87A-RASGRF1 Fusion in an Exceptional Responder to Sunitinib with Non-Small Cell Lung Cancer. Clin Cancer Res. 2020 Aug 1;26(15):4072-4079. doi: 10.1158/1078-0432.CCR-20-0397. Epub 2020 Apr 20.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: April 9, 2013
• First Submitted That Met QC Criteria: April 9, 2013
• First Posted (Estimate): April 11, 2013

Study Record Updates

• Last Update Posted (Actual): October 31, 2018
• Last Update Submitted That Met QC Criteria: October 3, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: 13-086