Sunitinib in Never-Smokers With Lung Adenocarcinoma

Status:	Completed
Conditions:	Lung Cancer, Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	11/2/2018
Start Date:	May 2013
End Date:	January 2018

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.

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).

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

We found this trial at

sites

Dana-Farber Cancer Institute

450 Brookline Ave
Boston, Massachusetts 2215

617-632-3000