Study of Erlotinib With or Without Investigational Drug (CS-7017) in Subjects With Advanced Non-small Cell Lung Cancer

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01101334
• Collaborator: (none)
• Enrollment: 90
• Locations: 17
• Arms: 2
• Duration (Months): 37
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 2 and open-label (subject will know the treatment he or she is receiving) study. The subject will receive either Erlotinib alone or Erlotinib + CS-7017 in this study.

The study will determine what effect adding CS-7017 to Erlotinib has on safety and length of survival in subjects with advanced non-small cell lung cancer who failed the first treatment.

Condition or Disease	Intervention/Treatment	Phase
Advanced Non-small Cell Lung Cancer (NSCLC)	Drug: CS-7017; Drug: erlotinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of CS-7017 and Erlotinib in Subjects With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CS-7017 plus erlotinib	Drug: CS-7017; CS-7017, Two 0.25mg Tablets administered twice daily; Drug: erlotinib; Erlotinib; One 150mg tablet administered once daily; Other Names: Tarceva
Active Comparator: erlotinib	Drug: erlotinib; Erlotinib; One 150mg tablet administered once daily; Other Names: Tarceva

Outcome Measures

Primary Outcome Measures

1. Summary of Analysis of Progression-Free Survival Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy [Baseline to disease progression or death, up to approximately 2.5 years]

   Progression-free survival (PFS) was defined as the time from randomization date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first.

Secondary Outcome Measures

1. Analysis of Overall Survival Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy [Baseline to death, up to approximately 2.5 years]

   Overall survival (OS) was defined as the time from randomization until death from any cause.

2. Overall Response Rate Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy [Baseline to disease progression or death, up to approximately 2.5 years]

   The overall response rate (ORR) was defined as the proportion of participants who achieved best overall response of complete response (CR) or partial response (PR); ORR = CR + PR. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

3. Summary of Treatment-Emergent Adverse Events (TEAEs) Occurring in ≥10% of Participants Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy [Baseline to 30 days after last dose, up to approximately 2.5 years]

   A treatment-emergent adverse event (TEAE) was defined as an adverse event that had an onset date on or after the first dose of CS-7017 or erlotinib up to and including 30 days after the last dose of any study drug, or worsened in severity after the first dose of CS-7017 or erlotinib relative to the pre-treatment state.

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 stage IIIB or IV NSCLC.

• Recurrent disease (either no response to treatment or subsequent relapse after an objective response) that has progressed after first line therapy.

• Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 criteria.

• ≥ 18 years of age.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

• Adequate organ and bone marrow function.

• Resolution of any toxic effects of prior therapy (except alopecia) to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0 grade ≤ 1.

• Agreement to use effective contraception while on treatment and for at least 3 months after end of treatment.

Exclusion Criteria:

• Treatment with anticancer therapy within 3 weeks before study treatment.

• Therapeutic or palliative radiation therapy within 2 weeks or major surgery within 4 weeks before study treatment (except for radiotherapy for brain metastases).

• Administration of other thiazolidinediones (TZDs) within 4 weeks before study treatment.

• Current need for concomitant use of other TZDs during the study.

• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection at time of screening.

• History of any of the following conditions within 6 months before initiating study treatment: diabetes mellitus requiring treatment with insulin or TZD agents; myocardial infarction with significant impairment of cardiac function; severe/unstable angina pectoris; coronary/peripheral artery bypass graft; New York Heart Association (NYHA) class III or IV congestive heart failure; malabsorption syndrome, chronic diarrhea (lasting > 4 weeks), inflammatory bowel disease, or partial bowel obstruction.

• Pericardial or pleural effusion (eg, requiring drainage) or pericardial involvement with the tumor. Participants with minimal pleural effusion may be eligible upon request by Investigator and approval by Sponsor.

• Pregnant or breast feeding.

• Prior treatment with epidermal growth factor receptor (EGFR) inhibitors.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	DHHA	Denver	Colorado	United States	80204
2	Gabrail Cancer Center	Canton	Ohio	United States	44718
3	Providence Regional Medical Center Everett	Everett	Washington	United States	98201
4	Zentrum fur Pneumologie und Thoraxchirurgie	Gauting		Germany	D-82131
5	King George Hospital	Visakhapatnam	Andhra Pradesh	India	530002
6	Vedanta Institute of Medical Sciences	Ahmedabad	Gujarat	India	380009
7	Kodlikeri Memorial Hospital	Aurangabad	Maharashtra	India	431001
8	Tata Memorial Hospital	Mumbai	Maharashtra	India	400012
9	Noble Hospital	Pune	Maharastra	India	411 013
10	Apollo Speciality Hospital	Chennai	Tamil Nadu	India	600 035
11	Meenakshi Mission Hospital	Madurai	Tamil Nadu	India	625107
12	Orchid Nursing Home	Kolkata	West Bengal	India	700 054
13	St. Vincent's Hospital	Gyeonggi-Do		Korea, Republic of	442-723
14	Hwasun Hospital	Jeonnam		Korea, Republic of	519-763
15	Severance Hospital	Seoul		Korea, Republic of	120-752
16	Samsung Medical Center	Seoul		Korea, Republic of	135-710
17	Asan Medical Center	Seoul		Korea, Republic of	138-736

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

• Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT01101334
• Other Study ID Numbers: CS7017-A-U204
• First Posted: Apr 9, 2010
• Last Update Posted: Jun 16, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Daiichi Sankyo, Inc.: NSCLC
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride; Efatutazone

Study Results

Participant Flow

Recruitment Details	A total of 90 participants who met all inclusion and no exclusion criteria were randomized to treatment; 89 participants received treatment.

Arm/Group Title	CS-7017 Plus Erlotinib	Erlotinib
Arm/Group Description	Participants who received two 0.25 mg CS-7017 tablets administered twice daily and one 150 mg erlotinib tablet administered once daily.	Participants who received one 150 mg erlotinib tablet administered once daily.
Period Title: Overall Study
STARTED	45	45
Received Study Treatment	44	45
COMPLETED	0	0
NOT COMPLETED	45	45

Baseline Characteristics

Arm/Group Title	CS-7017 Plus Erlotinib	Erlotinib	Total
Arm/Group Description	Participants who received two 0.25 mg CS-7017 tablets administered twice daily and one 150 mg erlotinib tablet administered once daily.	Participants who received one 150 mg erlotinib tablet administered once daily.	Total of all reporting groups
Overall Participants	44	45	89
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	33 75%	31 68.9%	64 71.9%
>=65 years	11 25%	14 31.1%	25 28.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.6 (10.36)	61.4 (11.34)	60.5 (10.85)
Sex: Female, Male (Count of Participants)
Female	11 25%	20 44.4%	31 34.8%
Male	33 75%	25 55.6%	58 65.2%

Outcome Measures

1. Primary Outcome

Title	Summary of Analysis of Progression-Free Survival Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy
Description	Progression-free survival (PFS) was defined as the time from randomization date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first.
Time Frame	Baseline to disease progression or death, up to approximately 2.5 years

Outcome Measure Data

Analysis Population Description

PFS was assessed in the Full Analysis Set.

Arm/Group Title	CS-7017 Plus Erlotinib	Erlotinib
Arm/Group Description	Participants who received two 0.25 mg CS-7017 tablets administered twice daily and one 150 mg erlotinib tablet administered once daily.	Participants who received one 150 mg erlotinib tablet administered once daily.
Measure Participants	44	45
Median (95% Confidence Interval) [months]	4.1	3.0

2. Secondary Outcome

Title	Analysis of Overall Survival Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy
Description	Overall survival (OS) was defined as the time from randomization until death from any cause.
Time Frame	Baseline to death, up to approximately 2.5 years

Outcome Measure Data

Analysis Population Description

OS was assessed in the Full Analysis Set.

Arm/Group Title	CS-7017 Plus Erlotinib	Erlotinib
Arm/Group Description	Participants who received two 0.25 mg CS-7017 tablets administered twice daily and one 150 mg erlotinib tablet administered once daily.	Participants who received one 150 mg erlotinib tablet administered once daily.
Measure Participants	44	45
Median (95% Confidence Interval) [months]	7.6	11.4

3. Secondary Outcome

Title	Overall Response Rate Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy
Description	The overall response rate (ORR) was defined as the proportion of participants who achieved best overall response of complete response (CR) or partial response (PR); ORR = CR + PR. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
Time Frame	Baseline to disease progression or death, up to approximately 2.5 years

Outcome Measure Data

Analysis Population Description

ORR was assessed in the Full Analysis Set.

Arm/Group Title	CS-7017 Plus Erlotinib	Erlotinib
Arm/Group Description	Participants who received two 0.25 mg CS-7017 tablets administered twice daily and one 150 mg erlotinib tablet administered once daily.	Participants who received one 150 mg erlotinib tablet administered once daily.
Measure Participants	44	45
Count of Participants [Participants]	9 20.5%	9 20%

4. Secondary Outcome

Title	Summary of Treatment-Emergent Adverse Events (TEAEs) Occurring in ≥10% of Participants Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy
Description	A treatment-emergent adverse event (TEAE) was defined as an adverse event that had an onset date on or after the first dose of CS-7017 or erlotinib up to and including 30 days after the last dose of any study drug, or worsened in severity after the first dose of CS-7017 or erlotinib relative to the pre-treatment state.
Time Frame	Baseline to 30 days after last dose, up to approximately 2.5 years

Outcome Measure Data

Analysis Population Description

TEAEs were assessed in the Safety Analysis Set.

Arm/Group Title	CS-7017 Plus Erlotinib	Erlotinib
Arm/Group Description	Participants who received two 0.25 mg CS-7017 tablets administered twice daily and one 150 mg erlotinib tablet administered once daily.	Participants who received one 150 mg erlotinib tablet administered once daily.
Measure Participants	44	45
Any TEAE	44 100%	43 95.6%
Blood and Lymphatic System Disorders	18 40.9%	4 8.9%
Anaemia	16 36.4%	3 6.7%
Cardiac Disorders	7 15.9%	2 4.4%
Eye Disorders	8 18.2%	3 6.7%
Gastrointestinal Disorders	27 61.4%	25 55.6%
Constipation	10 22.7%	3 6.7%
Diarrhea	18 40.9%	19 42.2%
Nausea	5 11.4%	7 15.6%
Stomatitis	6 13.6%	6 13.3%
General Disorders & Administration Site Conditions	41 93.2%	19 42.2%
Asthenia	9 20.5%	8 17.8%
Disease progression	8 18.2%	5 11.1%
Face edema	10 22.7%	0 0%
Fatigue	9 20.5%	5 11.1%
Noncardiac chest pain	5 11.4%	2 4.4%
Edema peripheral	17 38.6%	1 2.2%
Pyrexia	9 20.5%	3 6.7%
Infections and Infestations	13 29.5%	16 35.6%
Investigations	15 34.1%	12 26.7%
Weight increased	7 15.9%	1 2.2%
Metabolism and Nutrition Disorders	27 61.4%	15 33.3%
Decreased appetite	18 40.9%	10 22.2%
Hypokalemia	7 15.9%	1 2.2%
Musculoskeletal and Connective Tissue Disorders	15 34.1%	10 22.2%
Pain in extremity	7 15.9%	0 0%
Nervous System Disorders	15 34.1%	6 13.3%
Dizziness	5 11.4%	2 4.4%
Headache	5 11.4%	1 2.2%
Psychiatric Disorders	6 13.6%	5 11.1%
Respiratory, Thoracic, and Mediastinal Disoders	25 56.8%	17 37.8%
Cough	5 11.4%	3 6.7%
Dyspnea	9 20.5%	7 15.6%
Pleural effusion	10 22.7%	0 0%
Skin and Subcutaneous Tissue Disorders	33 75%	30 66.7%
Alopecia	5 11.4%	0 0%
Dermatitis acneiform	15 34.1%	9 20%
Dry skin	5 11.4%	7 15.6%
Pruritus	9 20.5%	11 24.4%
Rash	11 25%	15 33.3%
Swelling face	5 11.4%	1 2.2%
Vascular Disorders	1 2.3%	5 11.1%

Adverse Events

Time Frame	Treatment-emergent adverse event (TEAE) data were collected from time of signing the informed consent form to the end of study assessment and follow-up period (30 days after last dose of study drug), up to approximately 2.5 years.
Adverse Event Reporting Description	A TEAE was defined as an adverse event that had an onset date on or after the first dose of CS-7017 or erlotinib up to and including 30 days after the last dose of any study drug, or worsened in severity after the first dose of CS-7017 or erlotinib relative to the pre-treatment state. All-cause mortality includes all deaths caused by TEAEs.
Arm/Group Title	CS-7017 Plus Erlotinib		Erlotinib
Arm/Group Description	Participants who received two 0.25 mg CS-7017 tablets administered twice daily and one 150 mg erlotinib tablet administered once daily.		Participants who received one 150 mg erlotinib tablet administered once daily.
All Cause Mortality
	CS-7017 Plus Erlotinib		Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/44 (34.1%)		7/45 (15.6%)
Serious Adverse Events
	CS-7017 Plus Erlotinib		Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/44 (54.5%)		16/45 (35.6%)
Blood and lymphatic system disorders
Anaemia	5/44 (11.4%)		0/45 (0%)
Cardiac disorders
Acute myocardial infarction	1/44 (2.3%)		0/45 (0%)
Angina pectoris	1/44 (2.3%)		0/45 (0%)
Myocardial infarction	1/44 (2.3%)		0/45 (0%)
Pericardial effusion	2/44 (4.5%)		0/45 (0%)
Pericarditis	0/44 (0%)		1/45 (2.2%)
Gastrointestinal disorders
Diarrhea	1/44 (2.3%)		4/45 (8.9%)
Hematochezia	0/44 (0%)		1/45 (2.2%)
General disorders
Asthenia	1/44 (2.3%)		2/45 (4.4%)
Death	4/44 (9.1%)		1/45 (2.2%)
Disease progression	8/44 (18.2%)		5/45 (11.1%)
Multi-organ failure	1/44 (2.3%)		0/45 (0%)
Edema peripheral	2/44 (4.5%)		0/45 (0%)
Pain	0/44 (0%)		1/45 (2.2%)
Infections and infestations
Pneumonia	1/44 (2.3%)		2/45 (4.4%)
Respiratory tract infection	1/44 (2.3%)		0/45 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic pain	1/44 (2.3%)		0/45 (0%)
Non-small cell lung cancer	1/44 (2.3%)		0/45 (0%)
Paraneoplastic syndrome	1/44 (2.3%)		0/45 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/44 (2.3%)		1/45 (2.2%)
Pleural effusion	2/44 (4.5%)		0/45 (0%)
Pulmonary embolism	1/44 (2.3%)		0/45 (0%)
Vascular disorders
Femoral arterial stenosis	0/44 (0%)		1/45 (2.2%)
Macroangiopathy	0/44 (0%)		1/45 (2.2%)
Pelvic venous thrombosis	0/44 (0%)		1/45 (2.2%)
Vascular stenosis	0/44 (0%)		1/45 (2.2%)
Other (Not Including Serious) Adverse Events
	CS-7017 Plus Erlotinib		Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/44 (100%)		43/45 (95.6%)
Blood and lymphatic system disorders
Anaemia	16/44 (36.4%)		3/45 (6.7%)
Any Blood and Lymphatic System Disorders	18/44 (40.9%)		4/45 (8.9%)
Cardiac disorders
Any Cardiac Disorders	7/44 (15.9%)		2/45 (4.4%)
General disorders
Death	4/44 (9.1%)		1/45 (2.2%)
Disease progression	8/44 (18.2%)		5/45 (11.1%)
Fatigue	9/44 (20.5%)		5/45 (11.1%)
Any General Disorders & Administration Site Conditions	41/44 (93.2%)		19/45 (42.2%)
Investigations
Neutrophil count decreased	3/44 (6.8%)		0/45 (0%)
Any Investigations	15/44 (34.1%)		12/45 (26.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Any Neoplasms Benign, Malignant, and Unspecified (Including Cysts and Polyps)	4/44 (9.1%)		2/45 (4.4%)
Respiratory, thoracic and mediastinal disorders
Any Respiratory, Thoracic, and Mediastinal Disorders	25/44 (56.8%)		17/45 (37.8%)
Skin and subcutaneous tissue disorders
Any Skin and Subcutaneous Tissue Conditions	33/44 (75%)		30/45 (66.7%)

Limitations/Caveats

[Not Specified]

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.