Sunitinib in Never-Smokers With Lung Adenocarcinoma

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01829217
• Collaborator: (none)
• Enrollment: 13
• Locations: 4
• Arm: 1
• Duration (Months): 56
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

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
• 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 1, 2013
• Actual Primary Completion Date: Aug 1, 2017
• Actual Study Completion Date: Jan 1, 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) [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02214
2	Beth Isreal Deaconess Medical Center	Boston	Massachusetts	United States	02215
3	Brigham and Women's Hospital	Boston	Massachusetts	United States	02215
4	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)

• Study Protocol and Statistical Analysis Plan - Mar 18, 2015

More Information

Publications

None provided.

• Responsible Party: Geoffrey Oxnard, MD, Prinicipal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01829217
• Other Study ID Numbers: 13-086
• First Posted: Apr 11, 2013
• Last Update Posted: Oct 31, 2018
• Last Verified: Oct 1, 2018

• Additional relevant MeSH terms: Adenocarcinoma; Adenocarcinoma of Lung; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib
Arm/Group Description	42 day cycle, taken orally every day for the first 28 days followed by 14 days off Sunitinib
Period Title: Overall Study
STARTED	13
COMPLETED	13
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Sunitinib
Arm/Group Description	42 day cycle, taken orally every day for the first 28 days followed by 14 days off Sunitinib
Overall Participants	13
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Sex: Female, Male (Count of Participants)
Female	7 53.8%
Male	6 46.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.7%
Not Hispanic or Latino	12 92.3%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	Percentage of patients with evidence of complete or partial response per RECIST1.1 criteria.
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).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sunitinib
Arm/Group Description	42 day cycle, taken orally every day for the first 28 days followed by 14 days off Sunitinib
Measure Participants	13
Number (95% Confidence Interval) [percentage of participants]	7.69 59.2%

Adverse Events

Time Frame	Adverse events should be reported from start of study intervention through 30 days after the last dose of study treatment. AEs were assessed through January 23, 2017, approximately 44 months.
Adverse Event Reporting Description	Because this drug is commercially available, only grade 3 adverse events are reported here.
Arm/Group Title	Sunitinib
Arm/Group Description	42 day cycle, taken orally every day for the first 28 days followed by 14 days off Sunitinib
All Cause Mortality
	Sunitinib
	Affected / at Risk (%)	# Events
Total	7/13 (53.8%)
Serious Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Other (Not Including Serious) Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	9/13 (69.2%)
Blood and lymphatic system disorders
Anemia	2/13 (15.4%)	6
Febrile neutropenia	1/13 (7.7%)	1
Thrombotic thrombocytopenic purpura	3/13 (23.1%)	4
Cardiac disorders
Palpitations	1/13 (7.7%)	1
Endocrine disorders
Endocrine disorders - Other, specify	1/13 (7.7%)	3
Hyperthyroidism	3/13 (23.1%)	3
Hypothyroidism	1/13 (7.7%)	1
Eye disorders
Dry eye	2/13 (15.4%)	3
Eye pain	1/13 (7.7%)	1
Gastrointestinal disorders
Abdominal pain	1/13 (7.7%)	1
Constipation	6/13 (46.2%)	8
Diarrhea	5/13 (38.5%)	10
Dry mouth	2/13 (15.4%)	2
Dyspepsia	3/13 (23.1%)	3
Dysphagia	1/13 (7.7%)	1
Flatulence	1/13 (7.7%)	1
Gastritis	1/13 (7.7%)	1
Gastroesophageal reflux disease	2/13 (15.4%)	2
Gastrointestinal disorders - Other, specify	2/13 (15.4%)	4
Hemorrhoids	1/13 (7.7%)	1
Mucositis oral	6/13 (46.2%)	11
Nausea	6/13 (46.2%)	9
Oral dysesthesia	1/13 (7.7%)	1
Oral pain	1/13 (7.7%)	1
Rectal hemorrhage	1/13 (7.7%)	2
Vomiting	4/13 (30.8%)	7
General disorders
Edema limbs	3/13 (23.1%)	3
Flu like symptoms	1/13 (7.7%)	1
Localized edema	1/13 (7.7%)	1
Malaise	1/13 (7.7%)	1
Non-cardiac chest pain	2/13 (15.4%)	2
Pain	2/13 (15.4%)	3
Fatigue	9/13 (69.2%)	20
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify	1/13 (7.7%)	1
Infections and infestations
Infections and infestations - Other, specify	1/13 (7.7%)	3
Mucosal infection	1/13 (7.7%)	1
Stoma site infection	1/13 (7.7%)	4
Upper respiratory infection	1/13 (7.7%)	1
Urinary tract infection	1/13 (7.7%)	1
Injury, poisoning and procedural complications
Bruising	3/13 (23.1%)	3
Investigations
Alanine aminotransferase increased	1/13 (7.7%)	3
Alkaline phosphatase increased	1/13 (7.7%)	1
Aspartate aminotransferase increased	4/13 (30.8%)	5
Blood bilirubin increased	1/13 (7.7%)	1
Creatinine increased	1/13 (7.7%)	1
Lymphocyte count decreased	1/13 (7.7%)	1
Neutrophil count decreased	5/13 (38.5%)	11
Platelet count decreased	3/13 (23.1%)	8
Weight loss	2/13 (15.4%)	4
White blood cell decreased	5/13 (38.5%)	11
Metabolism and nutrition disorders
Anorexia	6/13 (46.2%)	9
Dehydration	2/13 (15.4%)	3
Glucose intolerance	1/13 (7.7%)	1
Hyperglycemia	3/13 (23.1%)	6
Hypoalbuminemia	1/13 (7.7%)	3
Hypocalcemia	1/13 (7.7%)	1
Hypokalemia	3/13 (23.1%)	4
Hypomagnesemia	2/13 (15.4%)	2
Hyponatremia	2/13 (15.4%)	2
Hypophosphatemia	3/13 (23.1%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	1/13 (7.7%)	2
Arthritis	1/13 (7.7%)	1
Back pain	2/13 (15.4%)	2
Bone pain	3/13 (23.1%)	3
Chest wall pain	1/13 (7.7%)	1
Muscle weakness upper limb	1/13 (7.7%)	1
Musculoskeletal and connective tissue disorder - Other, specify	1/13 (7.7%)	1
Myalgia	1/13 (7.7%)	1
Neck pain	1/13 (7.7%)	1
Pain in extremity	2/13 (15.4%)	8
Nervous system disorders
Ataxia	1/13 (7.7%)	1
Dizziness	2/13 (15.4%)	2
Dysgeusia	5/13 (38.5%)	6
Headache	2/13 (15.4%)	2
Nervous system disorders - Other, specify	1/13 (7.7%)	1
Peripheral motor neuropathy	1/13 (7.7%)	1
Psychiatric disorders
Anxiety	1/13 (7.7%)	1
Insomnia	2/13 (15.4%)	2
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/13 (7.7%)	1
Bronchopulmonary hemorrhage	1/13 (7.7%)	1
Cough	6/13 (46.2%)	8
Dyspnea	7/13 (53.8%)	7
Epistaxis	4/13 (30.8%)	4
Hoarseness	1/13 (7.7%)	1
Nasal congestion	1/13 (7.7%)	1
Respiratory, thoracic and mediastinal disorders	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Dry skin	3/13 (23.1%)	4
Palmar-plantar erythrodysesthesia syndrome	6/13 (46.2%)	11
Pruritus	1/13 (7.7%)	2
Rash acneiform	3/13 (23.1%)	3
Skin and subcutaneous tissue disorders - Other, specify	1/13 (7.7%)	1
Skin/subcutaneous tissue disorders; Other, specify	3/13 (23.1%)	3
Vascular disorders
Hypertension	3/13 (23.1%)	5

Limitations/Caveats

This study was closed to accrual due to slow enrollment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.