Safety and Efficacy Clinical Study of SNS-595 in Patients With Advanced Small Cell Lung Cancer

• Sponsor: Sunesis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00298896
• Collaborator: (none)
• Enrollment: 55
• Locations: 17
• Arm: 1
• Duration (Months): 28
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the objective tumor response rate to SNS-595 in patients with small cell lung cancer (SCLC).

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

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 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 Intravenous Administration of SNS-595 in Patients With Advanced Small Cell Lung Cancer (SCLC)
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Aug 1, 2007
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SNS-595 SNS-595; 48 mg/m2 administered IV once every 21 days for up to 6 cycles.	Drug: SNS-595; Other Names: Voreloxin Vosaroxin

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate [up to 6 months]

   Objective tumor response rate based on the RECIST criteria for target lesions as assessed by CT or MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD), at least a 20% increase in the sum of the LD of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Overall Response (OR) = CR + PR

Secondary Outcome Measures

1. Best Overall Response [upto 6 months]

   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), classified as CR, PR, SD or PD per RECIST criteria.

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 refractory SCLC requiring second-line chemotherapy who previously received first-line chemotherapy

• Measurable disease

• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2

• Brain metastasis may be included if the patient is neurologically stable and has been off steroids and anticonvulsants for at least 4 weeks prior to Cycle 1 Day 0

• 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, other than non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostatic intraepithelial neoplasia

• Q-wave myocardial infarction or cerebrovascular accident/transient ischemic attack (TIA) within 6 months before the first SNS-595 dose

• Thromboembolic event (deep vein thrombosis or pulmonary embolus) within 28 days 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, mitomycin C, and therapeutic monoclonal antibodies 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 25% of bone marrow reserve; radiation to the brain is permitted up to 28 days before the first SNS-595 dose, as long as the patient does not require treatment with corticosteroids for symptom control related to brain metastases.

• 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 or compliance with study procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis	Sacramento	California	United States	95817
2	Stanford University Medical Center	Stanford	California	United States	94305
3	Rush University Medical Center	Chicago	Illinois	United States	60612
4	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University	Baltimore	Maryland	United States	21231
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
7	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
8	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
9	Duke University Medical Center	Durham	North Carolina	United States	27705
10	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
11	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
12	The Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
13	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
14	BC Cancer Agency	Vancouver	British Columbia	Canada	V5Z 4E6
15	Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
16	Hopital Charles LeMoyne	Greenfield Park	Quebec	Canada	J4V 2H1
17	Hopital Laval	Sainte-Foy	Quebec	Canada	G1V 4G5

Sponsors and Collaborators

• Sunesis Pharmaceuticals

Investigators

• Study Director: Craig Berman, MD, Sunesis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunesis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00298896
• Other Study ID Numbers: SPO-0006
• First Posted: Mar 3, 2006
• Last Update Posted: Jul 26, 2018
• Last Verified: Oct 1, 2017

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

Study Results

Participant Flow

Arm/Group Title	SNS-595
Arm/Group Description	SNS-595; 48 mg/m2 administered IV once every 21 days for up to 6 cycles.
Period Title: Overall Study
STARTED	55
COMPLETED	5
NOT COMPLETED	50

Baseline Characteristics

Arm/Group Title	SNS-595
Arm/Group Description	SNS-595; 48 mg/m2 administered IV once every 21 days for up to 6 cycles.
Overall Participants	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (9.46)
Sex: Female, Male (Count of Participants)
Female	25 45.5%
Male	30 54.5%
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	1 1.8%
White	54 98.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Canada	14 25.5%
United States	41 74.5%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate
Description	Objective tumor response rate based on the RECIST criteria for target lesions as assessed by CT or MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD), at least a 20% increase in the sum of the LD of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Overall Response (OR) = CR + PR
Time Frame	up to 6 months

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population

Arm/Group Title	SNS-595
Arm/Group Description	SNS-595; 48 mg/m2 administered IV once every 21 days for up to 6 cycles.
Measure Participants	47
Count of Participants [Participants]	3 5.5%

2. Secondary Outcome

Title	Best Overall Response
Description	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), classified as CR, PR, SD or PD per RECIST criteria.
Time Frame	upto 6 months

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set

Arm/Group Title	SNS-595
Arm/Group Description	SNS-595; 48 mg/m2 administered IV once every 21 days for up to 6 cycles.
Measure Participants	47
Complete Response	1 1.8%
Partial Response	2 3.6%
Progressive Disease	31 56.4%
Stable Disease	13 23.6%

Adverse Events

Time Frame	From time of first dosing of study treatment (up to 6 cycles of 21 days each) to 28 days post last treatment, i.e., approximately 5.1 months.
Adverse Event Reporting Description	One enrolled patient removed from assessment due to error in admission to study (prior to study drug administration) and is therefore not included in the "Participants at Risk" data (54 of 55 participants).
Arm/Group Title	SNS-595
Arm/Group Description	SNS-595; 48 mg/m2 administered IV once every 21 days for up to 6 cycles. SNS-595
All Cause Mortality
	SNS-595
	Affected / at Risk (%)	# Events
Total	15/54 (27.8%)
Serious Adverse Events
	SNS-595
	Affected / at Risk (%)	# Events
Total	9/54 (16.7%)
Blood and lymphatic system disorders
Anaemia	1/54 (1.9%)
Febrile neutropenia	4/54 (7.4%)
Leukopenia	1/54 (1.9%)
Cardiac disorders
Atrial fibrillation	1/54 (1.9%)
General disorders
Sudden death	1/54 (1.9%)
Infections and infestations
Pneumonia	3/54 (5.6%)
Metabolism and nutrition disorders
Hyponatraemia	1/54 (1.9%)
Nervous system disorders
Leukoencephalopathy	1/54 (1.9%)
Skin and subcutaneous tissue disorders
Photosensitivity reaction	1/54 (1.9%)
Other (Not Including Serious) Adverse Events
	SNS-595
	Affected / at Risk (%)	# Events
Total	52/54 (96.3%)
Blood and lymphatic system disorders
Anaemia	9/54 (16.7%)
Iron deficiency anaemia	1/54 (1.9%)
Leukopenia	2/54 (3.7%)
Lymphadenopathy	1/54 (1.9%)
Neutropenia	21/54 (38.9%)
Thrombocytopenia	4/54 (7.4%)
WBC abnormal	1/54 (1.9%)
Cardiac disorders
Palpitations	1/54 (1.9%)
Supraventricular tachycardia	1/54 (1.9%)
Tachycardia	2/54 (3.7%)
Ear and labyrinth disorders
Hearing impaired	1/54 (1.9%)
Vertigo	1/54 (1.9%)
Eye disorders
Blindness transient	1/54 (1.9%)
Dry eye	1/54 (1.9%)
Vision blurred	2/54 (3.7%)
Gastrointestinal disorders
Abdominal pain	3/54 (5.6%)
Abdominal pain upper	2/54 (3.7%)
Breath odour	1/54 (1.9%)
Constipation	16/54 (29.6%)
Diarrhoea	10/54 (18.5%)
Dry mouth	2/54 (3.7%)
Dyspepsia	7/54 (13%)
Dysphagia	4/54 (7.4%)
Gastrooesophageal reflux disease	2/54 (3.7%)
Haemorrhoids	1/54 (1.9%)
Mouth ulceration	1/54 (1.9%)
Nausea	28/54 (51.9%)
Odynophagia	1/54 (1.9%)
Oral discomfort	1/54 (1.9%)
Stomatitis	2/54 (3.7%)
Vomiting	13/54 (24.1%)
General disorders
Asthenia	9/54 (16.7%)
Chest discomfort	1/54 (1.9%)
Chills	4/54 (7.4%)
Disease progression	6/54 (11.1%)
Fatigue	39/54 (72.2%)
Gait disturbances	1/54 (1.9%)
General physical health deterioration	1/54 (1.9%)
Hyperhidrosis	2/54 (3.7%)
Influenza like illness	1/54 (1.9%)
Lethargy	1/54 (1.9%)
Mucosal inflammation	4/54 (7.4%)
Nodule	1/54 (1.9%)
Non-cardiac chest pain	8/54 (14.8%)
Oedema peripheral	3/54 (5.6%)
Pain	4/54 (7.4%)
Pitting oedema	1/54 (1.9%)
Pyrexia	2/54 (3.7%)
Hepatobiliary disorders
Hepatomegaly	1/54 (1.9%)
Hyperbilirubinaemia	1/54 (1.9%)
Liver disorder	1/54 (1.9%)
Immune system disorders
Seasonal allergy	1/54 (1.9%)
Infections and infestations
Bronchitis	1/54 (1.9%)
Herpes simplex	1/54 (1.9%)
Laryngitis	1/54 (1.9%)
Localised infection	1/54 (1.9%)
Nasopharyngitis	2/54 (3.7%)
Oral candidiasis	2/54 (3.7%)
Otitis media	1/54 (1.9%)
Sinusitis	1/54 (1.9%)
Upper respiratory tract infection	2/54 (3.7%)
Urinary tract infection	2/54 (3.7%)
Injury, poisoning and procedural complications
Arthropod bite	1/54 (1.9%)
Blister	1/54 (1.9%)
Road traffic accident	1/54 (1.9%)
Investigations
Breath sounds abnormal	1/54 (1.9%)
Weight decreased	2/54 (3.7%)
Metabolism and nutrition disorders
Anorexia	10/54 (18.5%)
Decreased appetite	1/54 (1.9%)
Dehydration	5/54 (9.3%)
Diabetes mellitus	1/54 (1.9%)
Hypercalcaemia of malignancy	1/54 (1.9%)
Hyperglycaemia	2/54 (3.7%)
Hypokalaemia	4/54 (7.4%)
Hypomagnesaemia	2/54 (3.7%)
Hyponatraemia	5/54 (9.3%)
Polydipsia	1/54 (1.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/54 (13%)
Back pain	12/54 (22.2%)
Bone pain	1/54 (1.9%)
Bursitis	1/54 (1.9%)
Chest wall pain	1/54 (1.9%)
Flank pain	2/54 (3.7%)
Groin pain	1/54 (1.9%)
Muscle spasms	1/54 (1.9%)
Musculoskeletal chest pain	1/54 (1.9%)
Myalgia	2/54 (3.7%)
Neck pain	2/54 (3.7%)
Pain in extremity	2/54 (3.7%)
Shoulder pain	2/54 (3.7%)
Nervous system disorders
Akathisia	1/54 (1.9%)
Balance disorder	1/54 (1.9%)
Cognitive disorder	1/54 (1.9%)
Dizziness	6/54 (11.1%)
Dysgeusia	7/54 (13%)
Headache	8/54 (14.8%)
Memory impairment	1/54 (1.9%)
Neuropathy	2/54 (3.7%)
Neuropathy peripheral	1/54 (1.9%)
Paraesthesia	2/54 (3.7%)
Peripheral sensory neuropathy	1/54 (1.9%)
Somnolence	1/54 (1.9%)
Tremor	1/54 (1.9%)
Psychiatric disorders
Agitation	1/54 (1.9%)
Anxiety	2/54 (3.7%)
Confusional state	2/54 (3.7%)
Depression	3/54 (5.6%)
Insomnia	5/54 (9.3%)
Restlessness	1/54 (1.9%)
Renal and urinary disorders
Bladder distension	1/54 (1.9%)
Chromaturia	1/54 (1.9%)
Pollakiuria	2/54 (3.7%)
Proteinuria	1/54 (1.9%)
Pyuria	1/54 (1.9%)
Renal failure	2/54 (3.7%)
Urinary retention	2/54 (3.7%)
Urine abnormality	1/54 (1.9%)
Reproductive system and breast disorders
Vaginal discharge	1/54 (1.9%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/54 (1.9%)
Chronic respiratory failure	1/54 (1.9%)
Cough	11/54 (20.4%)
Dysphonia	3/54 (5.6%)
Dyspnoea	14/54 (25.9%)
Epistaxis	3/54 (5.6%)
Haemoptysis	2/54 (3.7%)
Hiccups	2/54 (3.7%)
Nasal congestion	2/54 (3.7%)
Pharyngolaryngeal pain	4/54 (7.4%)
Plerual effusion	1/54 (1.9%)
Pleuritic pain	1/54 (1.9%)
Postnasal drip	1/54 (1.9%)
Productive cough	2/54 (3.7%)
Rhinorrhoea	1/54 (1.9%)
Wheezing	1/54 (1.9%)
Skin and subcutaneous tissue disorders
Alopecia	5/54 (9.3%)
Dry skin	3/54 (5.6%)
Erythema	1/54 (1.9%)
Hair disorder	1/54 (1.9%)
Hyperhidrosis	2/54 (3.7%)
Periorbital oedema	1/54 (1.9%)
Photosensitivity reaction	1/54 (1.9%)
Pruritus	1/54 (1.9%)
Purpura	1/54 (1.9%)
Rash	6/54 (11.1%)
Rash erythematous	1/54 (1.9%)
Skin hyperpigmentation	1/54 (1.9%)
Skin odour abnormal	1/54 (1.9%)
Vascular disorders
Hypertension	1/54 (1.9%)
Hypotension	2/54 (3.7%)
Orthostatic hypotension	1/54 (1.9%)
Thrombophlebitis	1/54 (1.9%)

Limitations/Caveats

Further study is needed to confirm the results due to limited sampling size. Statistical fields are not included here because no statistical testings were performed to compare any of the treatment groups. 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.