Sunitinib in Never-Smokers With Lung Adenocarcinoma

• ClinicalTrials.gov Identifier: NCT01829217
• Recruitment Status: Completed
• First Posted: April 11, 2013
• Results First Posted: September 4, 2018
• Last Update Posted: October 31, 2018
• Sponsor: Dana-Farber Cancer Institute
• Information provided by (Responsible Party): Geoffrey Oxnard, MD, Dana-Farber Cancer Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer	Drug: Sunitinib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Sunitinib in Never-smokers With Lung Adenocarcinoma: Identification of Oncogenic Alterations Underlying Sunitinib Sensitivity
• Study Start Date: May 2013
• Actual Primary Completion Date: August 2017
• Actual Study Completion Date: January 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: 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). ]
   Percentage of patients with evidence of complete or partial response per RECIST1.1 criteria.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02214

Beth Isreal Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02215

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Dana-Farber Cancer Institute

Investigators

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

  Study Documents (Full-Text)

Documents provided by Geoffrey Oxnard, MD, Dana-Farber Cancer Institute:

Study Protocol and Statistical Analysis Plan  [PDF] March 18, 2015

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Geoffrey Oxnard, MD, Prinicipal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01829217
• Other Study ID Numbers: 13-086
• First Posted: April 11, 2013
• Results First Posted: September 4, 2018
• Last Update Posted: October 31, 2018
• Last Verified: October 2018

Additional relevant MeSH terms:

Adenocarcinoma; Adenocarcinoma of Lung; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Sunitinib; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action