Safety and Efficacy Clinical Study of SNS-595 for Second-Line Therapy in Patients With Advanced NSCLC

• Sponsor: Sunesis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00252382
• Collaborator: (none)
• Enrollment: 31
• Locations: 4
• Arm: 1
• Actual Duration (Months): 23.1
• Patients Per Site: 7.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the objective tumor response rate (based on the RECIST criteria) to SNS-595 as a second-line therapy in patients with advanced NSCLC.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: SNS-595 Injection	Phase 2

Detailed Description

Other objectives of this study are to assess the safety, tumor response, time to disease progression, survival rate and to explore several potential biomarkers to see how these levels change after administration of SNS-595.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Open-Label, Multicenter Clinical Study of the Safety and Efficacy of the Intravenous Administration of SNS-595 as Second-Line Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
• Actual Study Start Date: Dec 27, 2005
• Actual Primary Completion Date: Mar 5, 2007
• Actual Study Completion Date: Nov 29, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment with 48 mg/m2 of SNS-595 Patients are treated with 48 mg/m2 of the drug SNS-595 injection once every 21 days for up to 6 cycles as a second -line therapy to patients with advanced non-small cell lung cancer (NSCLC)	Drug: SNS-595 Injection; Vosaroxin (formerly voreloxin or SNS-595) is a first in class anticancer quinolone derivative, non anthracycline topoisomerase II inhibitor. It induces replication dependent DNA damage by intercalating DNA and inhibiting topoisomerase II, leading to apoptosis.; Other Names: Voreloxin Vosaroxin

Outcome Measures

Primary Outcome Measures

1. Objective Tumor Response Rate [168 days]

   ORR is based on RECIST criteria to SNS-595 as a second-line therapy in patients with advanced NSCLC. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Best Overall Response [168 days]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions; >=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions (PD); Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (SD). The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Able to understand and willing to sign a written informed consent document

• Patients who have recurrent or metastatic NSCLC, who have failed initial therapy with a platinum-containing regimen and have not received any second-line therapy (adjuvant therapy is acceptable if it was completed greater than or equal to 12 months before the cancer recurrence)

• Measurable disease

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

• Laboratory Values within the normal or reasonable reference range as specified by the protocol

Exclusion Criteria:

• Prior exposure to SNS-595

• Pregnant or breastfeeding

• Women of childbearing potential or male partners of women of childbearing potential unwilling to use an approved, effective means of contraception according to the institution's standards

• Other active malignancies or other malignancies within the past 12 months except non-melanoma skin cancer, cervical intraepithelial neoplasia or prostatic intraepithelial neoplasia

• Brain metastases, if present, without radiologic evidence of progressive disease for at least 3 months after completion of therapy

• Myocardial infarction, cerebrovascular accident/transient ischemic attack (TIA) or thromboembolic event (deep vein thrombosis or pulmonary embolus) within 6 months before the first SNS-595 dose

• Requires kidney dialysis (hemodialysis or peritoneal)

• Prior chemotherapy, investigational agents, or radiation therapy within 28 days before Cycle 1 Day 0; however, nitrosoureas and mitomycin are not permitted for at least 42 days before Cycle 1 Day 0

• In patients with toxicities caused by prior cancer therapy, those toxicities must have returned to less than or equal to Grade 1, with the exception of alopecia

• Prior pelvic radiation therapy or radiation to greater than or equal to 25% of bone marrow reserve (prior palliative radiation is permitted as long as it does not exceed 25% of bone marrow reserve)

• Any other medical, psychological, or social condition that, in the opinion of the Principal Investigator, would contraindicate the patient's participation in the clinical trial due to safety concerns or compliance with study procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Premiere Oncology of Arizona	Scottsdale	Arizona	United States	85260
2	Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
3	Duke Comprehensive Cancer Center, Duke University	Durham	North Carolina	United States	27705
4	Sarah Cannon Research Institute, LLC	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• Sunesis Pharmaceuticals

Investigators

• Study Director: Glenn Michelson, MD, Sunesis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunesis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00252382
• Other Study ID Numbers: SPO-0005
• First Posted: Nov 11, 2005
• Last Update Posted: Sep 24, 2018
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by Sunesis Pharmaceuticals: Lung; Squamous Cell; Large Cell; Adenocarcinoma; Carcinoma; Cancer
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung

Study Results

Participant Flow

Arm/Group Title	Treatment With 48 mg/m2 of SNS-595
Arm/Group Description	Patients are treated with 48 mg/m2 of the drug SNS-595 injection once every 21 days for up to 6 cycles as a second -line therapy to patients with advanced non-small cell lung cancer (NSCLC) SNS-595 Injection: Vosaroxin (formerly voreloxin or SNS-595) is a first in class anticancer quinolone derivative, non anthracycline topoisomerase II inhibitor. It induces replication dependent DNA damage by intercalating DNA and inhibiting topoisomerase II, leading to apoptosis.
Period Title: Overall Study
STARTED	31
COMPLETED	5
NOT COMPLETED	26

Baseline Characteristics

Arm/Group Title	Total
Arm/Group Description	Open label administration of SNS-595 48 mg/m2 treatment on day one of 21 day cycles, up to 6 cycles.
Overall Participants	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.4 (9.74)
Sex: Female, Male (Count of Participants)
Female	11 35.5%
Male	20 64.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 9.7%
White	28 90.3%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Objective Tumor Response Rate
Description	ORR is based on RECIST criteria to SNS-595 as a second-line therapy in patients with advanced NSCLC. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	168 days

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population

Arm/Group Title	Total
Arm/Group Description	SNS-595 48 mg/m2
Measure Participants	26
Count of Participants [Participants]	1 3.2%

2. Secondary Outcome

Title	Best Overall Response
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions; >=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions (PD); Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (SD). The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started).
Time Frame	168 days

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population

Arm/Group Title	Total
Arm/Group Description	SNS-595 48 mg/m2
Measure Participants	26
Partial Response	1 3.2%
Progressive Disease	17 54.8%
Stable Disease	8 25.8%

Adverse Events

Time Frame	196 days
Arm/Group Title	Total
Arm/Group Description	SNS-595 48 mg/m2
All Cause Mortality
	Total
	Affected / at Risk (%)	# Events
Total	14/31 (45.2%)
Serious Adverse Events
	Total
	Affected / at Risk (%)	# Events
Total	6/31 (19.4%)
Blood and lymphatic system disorders
Febrile neutropenia	1/31 (3.2%)
Leukopenia	1/31 (3.2%)
Gastrointestinal disorders
Abdominal pain	1/31 (3.2%)
Vomiting	1/31 (3.2%)
Infections and infestations
Pneumonia	2/31 (6.5%)
Pneumonia pneumococcal	1/31 (3.2%)
Psychiatric disorders
Depression	1/31 (3.2%)
Renal and urinary disorders
Renal failure	1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/31 (3.2%)
Other (Not Including Serious) Adverse Events
	Total
	Affected / at Risk (%)	# Events
Total	30/31 (96.8%)
Blood and lymphatic system disorders
Anaemia	11/31 (35.5%)
Febrile neutropenia	3/31 (9.7%)
Leukopenia	2/31 (6.5%)
Neutropenia	5/31 (16.1%)
Thrombocytopenia	2/31 (6.5%)
Cardiac disorders
Tachycardia	2/31 (6.5%)
Ear and labyrinth disorders
Vertigo	1/31 (3.2%)
Eye disorders
Dry eye	1/31 (3.2%)
Vision blurred	2/31 (6.5%)
Gastrointestinal disorders
Abdominal discomfort	1/31 (3.2%)
Abdominal pain	6/31 (19.4%)
Abdominal tenderness	1/31 (3.2%)
Constipation	8/31 (25.8%)
Diarrhoea	1/31 (3.2%)
Dysphagia	1/31 (3.2%)
Gastrooesophageal reflux disease	2/31 (6.5%)
Hiatus hernia	1/31 (3.2%)
Hypoaesthesia oral	1/31 (3.2%)
Intestinal obstruction	1/31 (3.2%)
Lip disorder	1/31 (3.2%)
Nausea	17/31 (54.8%)
Oesophagitis	1/31 (3.2%)
Proctalgia	1/31 (3.2%)
Rectal spasm	1/31 (3.2%)
Stomatitis	1/31 (3.2%)
Vomiting	6/31 (19.4%)
General disorders
Asthenia	4/31 (12.9%)
Chest discomfort	1/31 (3.2%)
Chills	1/31 (3.2%)
Disease progression	1/31 (3.2%)
Fatigue	21/31 (67.7%)
Non-cardiac chest pain	4/31 (12.9%)
Oedema peripheral	5/31 (16.1%)
Pain	1/31 (3.2%)
Pyrexia	1/31 (3.2%)
Infections and infestations
Fungal infection	1/31 (3.2%)
Nasopharyngitis	1/31 (3.2%)
Oral candidiasis	6/31 (19.4%)
Sinusitis	2/31 (6.5%)
Upper respiratory tract infection	1/31 (3.2%)
Urinary tract infection	1/31 (3.2%)
Investigations
Breath sounds abnormal	1/31 (3.2%)
Metabolism and nutrition disorders
Anorexia	6/31 (19.4%)
Decreased appetite	1/31 (3.2%)
Dehydration	4/31 (12.9%)
Failure to thrive	1/31 (3.2%)
Hypercalcaemia	1/31 (3.2%)
Hyperglycaemia	1/31 (3.2%)
Hypokalaemia	1/31 (3.2%)
Hypomagnesaemia	1/31 (3.2%)
Hyponatraemia	1/31 (3.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/31 (19.4%)
Back pain	4/31 (12.9%)
Bone pain	1/31 (3.2%)
Chest wall pain	2/31 (6.5%)
Flank pain	1/31 (3.2%)
Metastases to bone	1/31 (3.2%)
Muscle spasms	2/31 (6.5%)
Muscular weakness	1/31 (3.2%)
Myalgia	2/31 (6.5%)
Neck pain	1/31 (3.2%)
Osteoporosis	1/31 (3.2%)
Pain in extremity	2/31 (6.5%)
Shoulder pain	2/31 (6.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system	2/31 (6.5%)
Nervous system disorders
Coordination abnormal	1/31 (3.2%)
Dizziness	2/31 (6.5%)
Headache	1/31 (3.2%)
Metabolic Encephalopathy	1/31 (3.2%)
Migraine	1/31 (3.2%)
Sensory loss	1/31 (3.2%)
Sinus headache	1/31 (3.2%)
Somnolence	1/31 (3.2%)
Psychiatric disorders
Anxiety	1/31 (3.2%)
Confusional state	2/31 (6.5%)
Depression	4/31 (12.9%)
Insomnia	3/31 (9.7%)
Mental status changes	1/31 (3.2%)
Renal and urinary disorders
Dysuria	2/31 (6.5%)
Haematuria	1/31 (3.2%)
Micturition disorder	1/31 (3.2%)
Reproductive system and breast disorders
Erectile dysfunction	1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Cough	4/31 (12.9%)
Dyspnoea	3/31 (9.7%)
Epistaxis	2/31 (6.5%)
Pleurisy	1/31 (3.2%)
Productive cough	4/31 (12.9%)
Pulmonary embolism	1/31 (3.2%)
Sinus congestion	1/31 (3.2%)
Skin and subcutaneous tissue disorders
Alopecia	5/31 (16.1%)
Night sweats	2/31 (6.5%)
Rash	1/31 (3.2%)
Skin burning sensation	1/31 (3.2%)
Skin exfoliation	1/31 (3.2%)
Surgical and medical procedures
Nasal sinus drainage	1/31 (3.2%)
Vascular disorders
Deep vein thrombosis	1/31 (3.2%)

Limitations/Caveats

Statistical fields are not included here because no statistical testings were performed to compare any treatment group. No p-values or odds ratios were reported.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.