Second-Line Therapy Study For Potentially Platinum-Sensitive Relapsed Ovarian Cancer

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00316173
• Collaborator: (none)
• Enrollment: 77
• Locations: 22
• Arm: 1
• Duration (Months): 48
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study was designed to find the most effective and safest doses of both HYCAMTIN and CARBOPLATIN that can be given for the treatment of ovarian cancer. This study may allow researchers to determine the effectiveness of combining HYCAMTIN and CARBOPLATIN.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Neoplasms, Ovarian	Drug: topotecan; Drug: CARBOPLATIN	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Single-Arm, Phase II Study of IV Weekly (Days 1 and 8 Every 21 Days) HYCAMTIN in Combination With Carboplatin (Day 1 Every 21 Days) as Second-Line Therapy in Subjects With Potentially Platinum-Sensitive Relapsed Ovarian Cancer
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single-arm HYCAMTIN at a dose of 2.0 - 2.5mg/m2 on Days 1 and 8 every 21 days followed by carboplatin at AUC 5 on Day 1, every 21 days	Drug: topotecan; HYCAMTIN at a dose of 2.0 mg/m2 on Days 1 and 8 every 21 days followed by carboplatin at AUC 5 on Day 1; Drug: CARBOPLATIN; HYCAMTIN at a dose of 2.0 mg/m2 on Days 1 and 8 every 21 days followed by carboplatin at AUC 5 on Day 1

Outcome Measures

Primary Outcome Measures

1. Number of Participants With the Indicated Response [From start of treatment to evidence of CR or PR (up to 39.3 weeks).]

   Overall response rate, as determined by radiologic evaluation (utilizing the World Health Organization [WHO] criteria and/or physical examination was measured. Complete response (CR: complete disappearance of all lesions), partial response (PR: >50% decrease in the measurements of the largest lesions with no appearance of new lesions), stable disease (SD: no change in tumor size for at least 8 weeks) and progressive disease (PD: >25% increase in measurements of lesions or appearance of new lesions).

Secondary Outcome Measures

1. Time to Response [From start of treatment to evidence of PR or CR (up to 39.3 weeks)]

   Time to response was calculated as the time from start of treatment until first evidence of partial response (PR; >50% decrease in the measurements of the largest lesions with no appearance of new lesions) or complete response (CR; complete disappearance of all lesions).

2. Duration of Response [From time of PR or CR to disease progression/death (up to 56.0 weeks)]

   Duration of response was calculated as the time from first documented PR or CR until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was "censored".

3. Progression-free Survival [From start of treatment to disease progression/death (up to 67.7 weeks)]

   Progression-free survival (PFS) was calculated as the time from the start of treatment until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was "censored". Although "Time to Disease Progression" was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of "PFS". As such, "PFS" was measured, not "Time to Disease Progression".

4. Number of Participants Who Died From the Start of Treatment to Follow-up [From start of treatment to death (up to 110.4 weeks).]

   The number of participants who died from the start of treatment to follow-up was calculated. For participants who did not die, the date of last contact was used. The word used for such participants was "censored".

5. The Number of Participants Classified as Responders in Cancer Antigen 125 (CA-125) [Baseline to end of study (up to 54.7 weeks).]

   CA-125 is a "tumor marker", found in greater concentration in tumor cells than other cells of the body. Participants were classed as responders if their CA-125 level at the end of study was 50% or less of baseline. In addition, a confirmatory sample (taken at least 28 days after the first sample) must have also been 50% or less of baseline.

6. Time to Disease Progression [From start of treatment to disease progression/death]

   Although "Time to Disease Progression" was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of "Progression-free Survival". As such, "Progression-free Survival" was measured, not "Time to Disease Progression". See the outcome measure entitled "Progression-free Survival" for data pertaining to time to disease progression.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Subject must have baseline laboratory values as follows:

• Hemoglobin 9.0 g/dL

• Neutrophils 1,500/mm3

• Platelets 100,000/mm3

• Creatinine 1.5 mg/dL ( 133 mol/l) or creatinine clearance 60 mL/min

• Serum bilirubin < 2.0 mg/dL (< 35 umol/L)

• SGOT/AST, SGPT/ALT and alkaline phosphatase < 2 times ULN if liver metastases are absent by abdominal CT or MRI or < 5 times ULN if liver metastases are present

• Subject is allowed to have received, but is not required to have received, one additional prior non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition: Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction

• Subject is female 18 years of age with an ECOG Performance Status of 0, 1 or 2

• Subject has recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer which was histologically confirmed at the time of the primary diagnosis

• Subject has received one prior platinum-based chemotherapeutic regimen (containing either carboplatin or cisplatin) for the treatment of primary disease. Consolidation chemotherapy is not permitted

• Subject's disease is considered potentially platinum-sensitive (i.e., have had a platinum-free interval following complete response to carboplatin or cisplatin of greater than 6 months)

• Subject must have at least one measurable lesion as determined by diagnostic studies including CT or MRI or physical exam. Measurable disease must be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be 20 mm in their longest dimension when measured by conventional techniques, including palpation, plain X-ray, CT and MRI, or 10 mm when measured by spiral CT. Palpable tumor masses that cannot be evaluated radiologically must have 2 diameters 20 mm. An attempt to document lesion size by ultrasound should be undertaken for palpable lesions not visualized on CT (or MRI).

• The same diagnostic imaging method used to evaluate disease must be used throughout the study to evaluate lesions consistently

• Stable blood, liver and renal functions.

• Subjects of child-bearing potential must be practicing adequate contraception (e.g. oral contraceptives, diaphragm plus spermicide, or IUD) for at least 3 months prior to study start. The same contraceptive method should be used throughout the study and continue for at least 4 weeks after the end of the study

Exclusion criteria:

• Pregnant or lactating.

• Subject has received more than 1 prior chemotherapy regimen or a history of consolidation cytotoxic chemotherapy

• Subject has concomitant or history of previous malignancies, with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for 5 years

• Subject has brain metastases as documented by CT or MRI. Note: Asymptomatic subjects do not require CT or MRI to rule out brain metastases

• Received previous treatment with HYCAMTIN.

• Subject has received an investigational agent within 30 days or 5 half-lives (whichever is longer) prior to study entry

• Received prior radiation therapy for ovarian cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Los Angeles	California	United States	90033
2	GSK Investigational Site	Orange	California	United States	92868
3	GSK Investigational Site	Poway	California	United States	92064
4	GSK Investigational Site	Stanford	California	United States	94305
5	GSK Investigational Site	New Haven	Connecticut	United States	06520
6	GSK Investigational Site	Savannah	Georgia	United States	21404
7	GSK Investigational Site	South Bend	Indiana	United States	46617
8	GSK Investigational Site	Las Vegas	Nevada	United States	89109
9	GSK Investigational Site	Albany	New York	United States	12208
10	GSK Investigational Site	Brightwaters	New York	United States	11718
11	GSK Investigational Site	Chapel Hill	North Carolina	United States	27599-7570
12	GSK Investigational Site	Charlotte	North Carolina	United States	28203
13	GSK Investigational Site	Cleveland	Ohio	United States	44109-1998
14	GSK Investigational Site	Mayfield Heights	Ohio	United States	44124
15	GSK Investigational Site	Greenville	South Carolina	United States	29605
16	GSK Investigational Site	Salt Lake City	Utah	United States	84112-5550
17	GSK Investigational Site	Seattle	Washington	United States	98101
18	GSK Investigational Site	Milwaukee	Wisconsin	United States	53215
19	GSK Investigational Site	Calgary	Alberta	Canada	T2N 4N2
20	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4M1
21	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1H 5N4
22	GSK Investigational Site	Quebec		Canada	G1R 2J6

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

• Rose PG, Monk BJ, Provencher D, Hartney J, Legenne P, Lane S. An open-label, single-arm Phase II study of intravenous weekly (Days 1 and 8) topotecan in combination with carboplatin (Day 1) every 21 days as second-line therapy in patients with platinum-sensitive relapsed ovarian cancer. Gynecol Oncol. 2011 Jan;120(1):38-42. doi: 10.1016/j.ygyno.2010.10.011. Epub 2010 Nov 5.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00316173
• Other Study ID Numbers: 104864/902
• First Posted: Apr 20, 2006
• Last Update Posted: Nov 27, 2012
• Last Verified: Nov 1, 2012

• Keywords provided by GlaxoSmithKline: HYCAMTIN; ovarian cancer; recurrent; relapsed; carboplatin; topotecan; potentially platinum-sensitive
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Hypersensitivity; Carboplatin; Topotecan

Study Results

Participant Flow

Pre-assignment Detail	The run-in phase was conducted to find a safe dose of drug, before the treatment phase of the study began. Different doses were given to 22 participants (enrolled a few at a time) to find the safest dose. Once the safe dose was found, 55 new participants were enrolled in the treatment phase, and all were to start their treatment at this safe dose.

Arm/Group Title	Dose-finding Phase	Activity Assessment Phase
Arm/Group Description	Starting dose of 2.0 milligrams (mg)/square meter (m2) topotecan (Days 1 and 8, every 21 days) and area under the curve (AUC) 5 carboplatin (Day 1 every 21 days)	Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Period Title: Run-in Phase
STARTED	22	0
COMPLETED	15	0
NOT COMPLETED	7	0
Period Title: Run-in Phase
STARTED	0	55
COMPLETED	0	13
NOT COMPLETED	0	42

Baseline Characteristics

Arm/Group Title	Dose-finding Phase	Activity Assessment Phase	Total
Arm/Group Description	Starting dose of 2.0 milligrams (mg)/square meter (m2) topotecan (Days 1 and 8, every 21 days) and area under the curve (AUC) 5 carboplatin (Day 1 every 21 days)	Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.	Total of all reporting groups
Overall Participants	22	55	77
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.8 (10.94)	62.2 (11.13)	62.6 (11.03)
Sex: Female, Male (Count of Participants)
Female	22 100%	55 100%	77 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage	2 9.1%	2 3.6%	4 5.2%
American Indian or Alaska Native	0 0%	1 1.8%	1 1.3%
Asian	1 4.5%	3 5.5%	4 5.2%
White	19 86.4%	48 87.3%	67 87%
Missing	0 0%	1 1.8%	1 1.3%
Number of participants with the indicated ECOG Performance Status (participants) [Number]
Grade 0	15 68.2%	42 76.4%	57 74%
Grade 1	7 31.8%	9 16.4%	16 20.8%
Grade 2	0 0%	4 7.3%	4 5.2%

Outcome Measures

1. Secondary Outcome

Title	Time to Response
Description	Time to response was calculated as the time from start of treatment until first evidence of partial response (PR; >50% decrease in the measurements of the largest lesions with no appearance of new lesions) or complete response (CR; complete disappearance of all lesions).
Time Frame	From start of treatment to evidence of PR or CR (up to 39.3 weeks)

Outcome Measure Data

Analysis Population Description

All participants who showed a tumor response (CR or PR).

Arm/Group Title	Activity Assessment Phase
Arm/Group Description	Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Measure Participants	17
Median (95% Confidence Interval) [weeks]	6.57

2. Secondary Outcome

Title	Duration of Response
Description	Duration of response was calculated as the time from first documented PR or CR until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was "censored".
Time Frame	From time of PR or CR to disease progression/death (up to 56.0 weeks)

Outcome Measure Data

Analysis Population Description

All participants who showed a tumor response (CR or PR).

Arm/Group Title	Activity Assessment Phase
Arm/Group Description	Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Measure Participants	17
Median (95% Confidence Interval) [weeks]	42.64

3. Primary Outcome

Title	Number of Participants With the Indicated Response
Description	Overall response rate, as determined by radiologic evaluation (utilizing the World Health Organization [WHO] criteria and/or physical examination was measured. Complete response (CR: complete disappearance of all lesions), partial response (PR: >50% decrease in the measurements of the largest lesions with no appearance of new lesions), stable disease (SD: no change in tumor size for at least 8 weeks) and progressive disease (PD: >25% increase in measurements of lesions or appearance of new lesions).
Time Frame	From start of treatment to evidence of CR or PR (up to 39.3 weeks).

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug

Arm/Group Title	Activity Assessment Phase
Arm/Group Description	Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Measure Participants	55
Complete response	6 27.3%
Partial response	11 50%
Stable disease	20 90.9%
Progressive disease	7 31.8%
Not evaluable	11 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Activity Assessment Phase
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants with CR+PR
	Estimated Value	30.9
	Confidence Interval	() 95%; 18.7 to 43.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) was calculated as the time from the start of treatment until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was "censored". Although "Time to Disease Progression" was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of "PFS". As such, "PFS" was measured, not "Time to Disease Progression".
Time Frame	From start of treatment to disease progression/death (up to 67.7 weeks)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug

Arm/Group Title	Activity Assessment Phase
Arm/Group Description	Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Measure Participants	55
Median (95% Confidence Interval) [weeks]	44.29

5. Secondary Outcome

Title	Number of Participants Who Died From the Start of Treatment to Follow-up
Description	The number of participants who died from the start of treatment to follow-up was calculated. For participants who did not die, the date of last contact was used. The word used for such participants was "censored".
Time Frame	From start of treatment to death (up to 110.4 weeks).

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug

Arm/Group Title	Activity Assessment Phase
Arm/Group Description	Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Measure Participants	55
Died	8 36.4%
Censored	47 213.6%

6. Secondary Outcome

Title	The Number of Participants Classified as Responders in Cancer Antigen 125 (CA-125)
Description	CA-125 is a "tumor marker", found in greater concentration in tumor cells than other cells of the body. Participants were classed as responders if their CA-125 level at the end of study was 50% or less of baseline. In addition, a confirmatory sample (taken at least 28 days after the first sample) must have also been 50% or less of baseline.
Time Frame	Baseline to end of study (up to 54.7 weeks).

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug

Arm/Group Title	Activity Assessment Phase
Arm/Group Description	Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Measure Participants	55
Number [participants]	23 104.5%

7. Secondary Outcome

Title	Time to Disease Progression
Description	Although "Time to Disease Progression" was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of "Progression-free Survival". As such, "Progression-free Survival" was measured, not "Time to Disease Progression". See the outcome measure entitled "Progression-free Survival" for data pertaining to time to disease progression.
Time Frame	From start of treatment to disease progression/death

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who received at least one dose of study drug

Arm/Group Title	Activity Assessment Phase
Arm/Group Description	Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	Adverse events that were rounded up to 5% in the CSR (e.g. 1/22; 4.54%) are also included here.
Arm/Group Title	Dose-finding Phase		Activity Assessment Phase
Arm/Group Description	Starting dose of 2.0 milligrams (mg)/square meter (m2) topotecan (Days 1 and 8, every 21 days) and area under the curve (AUC) 5 carboplatin (Day 1 every 21 days)		Topotecan 2.5 mg/m2 (starting dose determined from the dose-finding phase) administered as a 30 minute intravenous (IV) infusion on Days 1 and 8, every 21 days. Carboplatin AUC 5 administered as a 30 minute IV infusion on Day 1, every 21 days.
All Cause Mortality
	Dose-finding Phase		Activity Assessment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dose-finding Phase		Activity Assessment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/22 (27.3%)		12/55 (21.8%)
Blood and lymphatic system disorders
Anemia	1/22 (4.5%)		2/55 (3.6%)
Neutropenia	1/22 (4.5%)		1/55 (1.8%)
Thrombocytopenia	0/22 (0%)		2/55 (3.6%)
Cardiac disorders
Angina pectoris	0/22 (0%)		1/55 (1.8%)
Gastrointestinal disorders
Enterovesical fistula	1/22 (4.5%)		0/55 (0%)
Abdominal pain	0/22 (0%)		2/55 (3.6%)
Small intestinal obstruction	0/22 (0%)		1/55 (1.8%)
General disorders
Pyrexia	1/22 (4.5%)		1/55 (1.8%)
Immune system disorders
Hypersensitivity	1/22 (4.5%)		0/55 (0%)
Drug hypersensitivity	0/22 (0%)		1/55 (1.8%)
Infections and infestations
Diverticulitis	1/22 (4.5%)		0/55 (0%)
Urinary tract infection	1/22 (4.5%)		0/55 (0%)
Metabolism and nutrition disorders
Hypomagnesemia	0/22 (0%)		1/55 (1.8%)
Musculoskeletal and connective tissue disorders
Back pain	0/22 (0%)		1/55 (1.8%)
Gouty arthritis	0/22 (0%)		1/55 (1.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone	0/22 (0%)		1/55 (1.8%)
Metastases to soft tissue	0/22 (0%)		1/55 (1.8%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/22 (4.5%)		0/55 (0%)
Dyspnea	0/22 (0%)		1/55 (1.8%)
Vascular disorders
Thrombosis	1/22 (4.5%)		0/55 (0%)
Vena cava thrombosis	1/22 (4.5%)		0/55 (0%)
Peripheral embolism	0/22 (0%)		1/55 (1.8%)
Other (Not Including Serious) Adverse Events
	Dose-finding Phase		Activity Assessment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/22 (90.9%)		54/55 (98.2%)
Blood and lymphatic system disorders
Anemia	1/22 (4.5%)		0/55 (0%)
Febrile neutropenia	1/22 (4.5%)		0/55 (0%)
Neutropenia	1/22 (4.5%)		5/55 (9.1%)
Cardiac disorders
Palpitations	2/22 (9.1%)		5/55 (9.1%)
Atrial fibrillation	1/22 (4.5%)		0/55 (0%)
Ear and labyrinth disorders
Ear pain	1/22 (4.5%)		0/55 (0%)
Ear pruritis	1/22 (4.5%)		0/55 (0%)
Eye disorders
Vision blurred	1/22 (4.5%)		2/55 (3.6%)
Gastrointestinal disorders
Constipation	12/22 (54.5%)		21/55 (38.2%)
Nausea	10/22 (45.5%)		40/55 (72.7%)
Diarrhea	6/22 (27.3%)		13/55 (23.6%)
Abdominal pain	4/22 (18.2%)		9/55 (16.4%)
Dyspepsia	3/22 (13.6%)		6/55 (10.9%)
Vomiting	3/22 (13.6%)		16/55 (29.1%)
Abdominal pain upper	1/22 (4.5%)		1/55 (1.8%)
Abdominal discomfort	1/22 (4.5%)		0/55 (0%)
Abdominal distension	1/22 (4.5%)		1/55 (1.8%)
Dry mouth	1/22 (4.5%)		4/55 (7.3%)
Frequent bowel movements	1/22 (4.5%)		0/55 (0%)
Stomatitis	1/22 (4.5%)		5/55 (9.1%)
General disorders
Fatigue	14/22 (63.6%)		42/55 (76.4%)
Adverse drug reaction	2/22 (9.1%)		1/55 (1.8%)
Pyrexia	1/22 (4.5%)		3/55 (5.5%)
Asthenia	1/22 (4.5%)		1/55 (1.8%)
Catheter site related reaction	1/22 (4.5%)		1/55 (1.8%)
Chest discomfort	1/22 (4.5%)		0/55 (0%)
Malaise	1/22 (4.5%)		0/55 (0%)
Pain	1/22 (4.5%)		0/55 (0%)
Chest pain	0/22 (0%)		4/55 (7.3%)
Mucosal inflammation	0/22 (0%)		3/55 (5.5%)
Hepatobiliary disorders
Cholelithiasis	1/22 (4.5%)		0/55 (0%)
Immune system disorders
Drug hypersensitivity	2/22 (9.1%)		12/55 (21.8%)
Infections and infestations
Urinary tract infection	2/22 (9.1%)		7/55 (12.7%)
Nasopharyngitis	2/22 (9.1%)		4/55 (7.3%)
Upper respiratory tract infection	2/22 (9.1%)		2/55 (3.6%)
Cellulitis	1/22 (4.5%)		1/55 (1.8%)
Eye infection staphylococcal	1/22 (4.5%)		0/55 (0%)
Fungal skin infection	1/22 (4.5%)		0/55 (0%)
Peridiverticular abscess	1/22 (4.5%)		0/55 (0%)
Rhinitis	1/22 (4.5%)		1/55 (1.8%)
Injury, poisoning and procedural complications
Foot fracture	1/22 (4.5%)		0/55 (0%)
Ligament rupture	1/22 (4.5%)		0/55 (0%)
Contusion	0/22 (0%)		3/55 (5.5%)
Metabolism and nutrition disorders
Anorexia	5/22 (22.7%)		11/55 (20%)
Hypomagnesemia	3/22 (13.6%)		10/55 (18.2%)
Hypokalemia	0/22 (0%)		5/55 (9.1%)
Decreased appetite	0/22 (0%)		4/55 (7.3%)
Dehydration	0/22 (0%)		3/55 (5.5%)
Musculoskeletal and connective tissue disorders
Muscle spasms	2/22 (9.1%)		2/55 (3.6%)
Arthralgia	1/22 (4.5%)		3/55 (5.5%)
Bursitis	1/22 (4.5%)		0/55 (0%)
Musculoskeletal pain	1/22 (4.5%)		3/55 (5.5%)
Myalgia	1/22 (4.5%)		2/55 (3.6%)
Pain in extremity	1/22 (4.5%)		5/55 (9.1%)
Back pain	0/22 (0%)		5/55 (9.1%)
Muscular weakness	0/22 (0%)		5/55 (9.1%)
Nervous system disorders
Headache	4/22 (18.2%)		15/55 (27.3%)
Dizziness	4/22 (18.2%)		9/55 (16.4%)
Dysgeusia	3/22 (13.6%)		6/55 (10.9%)
Neuropathy peripheral	2/22 (9.1%)		9/55 (16.4%)
Memory impairment	1/22 (4.5%)		0/55 (0%)
Paresthesia	1/22 (4.5%)		3/55 (5.5%)
Peripheral sensory neuropathy	1/22 (4.5%)		2/55 (3.6%)
Psychiatric disorders
Insomnia	3/22 (13.6%)		9/55 (16.4%)
Anxiety	1/22 (4.5%)		2/55 (3.6%)
Libido decreased	1/22 (4.5%)		0/55 (0%)
Renal and urinary disorders
Dysuria	1/22 (4.5%)		2/55 (3.6%)
Urine abnormality	1/22 (4.5%)		0/55 (0%)
Pollakiuria	0/22 (0%)		3/55 (5.5%)
Reproductive system and breast disorders
Vulvovaginal dryness	1/22 (4.5%)		0/55 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/22 (13.6%)		13/55 (23.6%)
Epistaxis	2/22 (9.1%)		4/55 (7.3%)
Cough	1/22 (4.5%)		5/55 (9.1%)
Dyspnea exertional	1/22 (4.5%)		1/55 (1.8%)
Painful respiration	1/22 (4.5%)		1/55 (1.8%)
Sneezing	0/22 (0%)		3/55 (5.5%)
Skin and subcutaneous tissue disorders
Alopecia	3/22 (13.6%)		9/55 (16.4%)
Pruritis	3/22 (13.6%)		2/55 (3.6%)
Rash	3/22 (13.6%)		4/55 (7.3%)
Erythema	1/22 (4.5%)		1/55 (1.8%)
Rash generalised	1/22 (4.5%)		0/55 (0%)
Vascular disorders
Flushing	2/22 (9.1%)		4/55 (7.3%)
Hypertension	1/22 (4.5%)		2/55 (3.6%)

Limitations/Caveats

As only 17 of 55 participants had CR/PR, the treatment was not effective. The follow up of participants for survival was thus stopped early (original plan: every 3 months for 2 years; then every 6 months for 3-5 years; then annually/until death).

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.