Trial Outcomes & Findings for Pazopanib Plus Lapatinib Compared to Lapatinib Alone and Pazopanib Alone In Subjects With Metastatic Cervical Cancer (NCT NCT00430781)

Last Updated: 2015-05-08

Results Overview

PFS is defined as the interval between the date of randomization and the date of disease progression or death due to any cause. The study was designed to test Combination vs. Lapatinib first. The result indicated that Combination would not show improvement over Lapatinib even if followed until the final analysis and the Combination arm was terminated. The monotherapy arms continued to the final analysis. Data shown here are from this interim analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

228 participants

Primary outcome timeframe

From randomization until at least 35 PFS events in pairwise comparison of the three treatment arms (Interim Analysis; up to 52.14 weeks)

Results posted on

2015-05-08

Participant Flow

Participants (par.) continued to be enrolled into all three treatment arms after clinical data cutoff for the interim analysis, but before the results were evaluated. Final total enrollment was 228 participants: 76 in the combination arm, 78 in the lapatinib monotherapy arm, and 74 in the pazopanib monotherapy arm.

Study was initially designed and started as a randomized, three-arm, controlled trial. Participants were randomized to the combination of pazopanib plus lapatinib, pazopanib monotherapy, or lapatinib monotherapy. Based on results from a planned interim analysis, the combination group was terminated, but the monotherapy groups continued as planned.

Participant milestones

Participant milestones
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy 800 mg (2 x 400 mg tablets) of oral pazopanib daily
Interim Analysis; 11 February 2008 STARTED	59	58	60
Interim Analysis; 11 February 2008 Ongoing	23	20	25
Interim Analysis; 11 February 2008 COMPLETED	0	0	0
Interim Analysis; 11 February 2008 NOT COMPLETED	59	58	60
Final Analysis; 31 July 2008 STARTED	0	78	74
Final Analysis; 31 July 2008 Ongoing	0	29	32
Final Analysis; 31 July 2008 COMPLETED	0	39	26
Final Analysis; 31 July 2008 NOT COMPLETED	0	39	48
End-of-Study Analysis; 28 July 2011 STARTED	77	77	74
End-of-Study Analysis; 28 July 2011 COMPLETED	53	59	54
End-of-Study Analysis; 28 July 2011 NOT COMPLETED	24	18	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy 800 mg (2 x 400 mg tablets) of oral pazopanib daily
Interim Analysis; 11 February 2008 Adverse Event	10	3	7
Interim Analysis; 11 February 2008 Lost to Follow-up	1	0	1
Interim Analysis; 11 February 2008 Protocol Violation	0	1	0
Interim Analysis; 11 February 2008 Withdrawal by Subject	4	0	2
Interim Analysis; 11 February 2008 Sponsor Terminated Study	1	0	0
Interim Analysis; 11 February 2008 Disease Progression	16	30	22
Interim Analysis; 11 February 2008 Death	0	1	0
Interim Analysis; 11 February 2008 Par. Withdrew; Followed for Survival	2	0	0
Interim Analysis; 11 February 2008 Physician Decision	2	3	3
Interim Analysis; 11 February 2008 Ongoing	23	20	25
Final Analysis; 31 July 2008 Lost to Follow-up	0	0	3
Final Analysis; 31 July 2008 Protocol Violation	0	1	0
Final Analysis; 31 July 2008 Withdrawal by Subject	0	2	7
Final Analysis; 31 July 2008 Physician Decision	0	6	6
Final Analysis; 31 July 2008 Other	0	1	0
Final Analysis; 31 July 2008 Ongoing	0	29	32
End-of-Study Analysis; 28 July 2011 Lost to Follow-up	5	3	3
End-of-Study Analysis; 28 July 2011 Protocol Violation	0	1	0
End-of-Study Analysis; 28 July 2011 Withdrawal by Subject	7	2	7
End-of-Study Analysis; 28 July 2011 Sponsor Terminated Study	4	5	4
End-of-Study Analysis; 28 July 2011 Physician Decision	4	6	6
End-of-Study Analysis; 28 July 2011 Other	4	1	0

Baseline Characteristics

Pazopanib Plus Lapatinib Compared to Lapatinib Alone and Pazopanib Alone In Subjects With Metastatic Cervical Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg n=59 Participants Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy n=58 Participants 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy n=60 Participants 800 mg (2 x 400 mg tablets) of oral pazopanib daily	Total n=177 Participants Total of all reporting groups
Age, Continuous	NA years STANDARD_DEVIATION NA • n=93 Participants	49.2 years STANDARD_DEVIATION 11.27 • n=4 Participants	50.8 years STANDARD_DEVIATION 10.93 • n=27 Participants	50 years STANDARD_DEVIATION 11.1 • n=483 Participants
Sex: Female, Male Female	59 Participants n=93 Participants	58 Participants n=4 Participants	60 Participants n=27 Participants	177 Participants n=483 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Gender Female	NA participants n=93 Participants	78 participants n=4 Participants	74 participants n=27 Participants	152 participants n=483 Participants
Gender Male	NA participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants
Race/Ethnicity, Customized African American	NA participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants
Race/Ethnicity, Customized American Indian	NA participants n=93 Participants	10 participants n=4 Participants	13 participants n=27 Participants	23 participants n=483 Participants
Race/Ethnicity, Customized Asian-South East	NA participants n=93 Participants	13 participants n=4 Participants	9 participants n=27 Participants	22 participants n=483 Participants
Race/Ethnicity, Customized White	NA participants n=93 Participants	52 participants n=4 Participants	52 participants n=27 Participants	104 participants n=483 Participants
Race/Ethnicity, Customized Asian-Central , South	NA participants n=93 Participants	2 participants n=4 Participants	0 participants n=27 Participants	2 participants n=483 Participants
Histology at diagnosis: Interim Analysis Adenocarcinoma	15 participants n=93 Participants	8 participants n=4 Participants	8 participants n=27 Participants	31 participants n=483 Participants
Histology at diagnosis: Interim Analysis Adenosquamous carcinoma	0 participants n=93 Participants	4 participants n=4 Participants	3 participants n=27 Participants	7 participants n=483 Participants
Histology at diagnosis: Interim Analysis Squamous cell carcinoma	32 participants n=93 Participants	38 participants n=4 Participants	43 participants n=27 Participants	113 participants n=483 Participants
Histology at diagnosis: Interim Analysis Other	10 participants n=93 Participants	8 participants n=4 Participants	5 participants n=27 Participants	23 participants n=483 Participants
Histology at diagnosis: Interim Analysis Missing	2 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	3 participants n=483 Participants
Histology at diagnosis: Final Anaysis Adenocarcinoma	NA participants n=93 Participants	11 participants n=4 Participants	12 participants n=27 Participants	23 participants n=483 Participants
Histology at diagnosis: Final Anaysis Adenosquamous carcinoma	NA participants n=93 Participants	4 participants n=4 Participants	3 participants n=27 Participants	7 participants n=483 Participants
Histology at diagnosis: Final Anaysis Squamous cell carcinoma	NA participants n=93 Participants	55 participants n=4 Participants	53 participants n=27 Participants	108 participants n=483 Participants
Histology at diagnosis: Final Anaysis Other	NA participants n=93 Participants	8 participants n=4 Participants	6 participants n=27 Participants	14 participants n=483 Participants

PRIMARY outcome

Timeframe: From randomization until at least 35 PFS events in pairwise comparison of the three treatment arms (Interim Analysis; up to 52.14 weeks)

Population: Intent to Treat (ITT) Population: all randomized participants

Outcome measures

Outcome measures
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg n=59 Participants Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy n=58 Participants 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy n=60 Participants 800 mg (2 x 400 mg tablets) of oral pazopanib daily
Progression-free Survival (PFS) in Interim Analysis	12.6 Weeks Interval 11.7 to 14.1	12.6 Weeks Interval 11.6 to 18.3	17.9 Weeks Interval 12.1 to 23.9

PRIMARY outcome

Timeframe: From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)

Population: ITT Population

PFS is defined as the interval between the date of randomization and the date of disease progression or death due to any cause. This study began as a 3-arm study. The combination arm was terminated at the interim analysis. The monotherapy arms continued to final analysis. Data shown here are from the final analysis.

Outcome measures

Outcome measures
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg n=78 Participants Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy n=74 Participants 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy 800 mg (2 x 400 mg tablets) of oral pazopanib daily
Progression-free Survival (PFS) in Final Analysis	17.1 Weeks Interval 12.1 to 18.1	18.1 Weeks Interval 15.1 to 24.6	—

SECONDARY outcome

Timeframe: From Randomization (11 December 2006) until approximately 78% overall survival events at the time of the second overall survival update (3 March 2010) (up to 168.29 weeks)

Population: ITT Population

Overall survival is defined as the time from randomization until death due to any cause.

Outcome measures

Outcome measures
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg n=78 Participants Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy n=74 Participants 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy 800 mg (2 x 400 mg tablets) of oral pazopanib daily
Overall Survival	44.1 Weeks Interval 35.6 to 48.9	49.7 Weeks Interval 42.0 to 55.9	—

SECONDARY outcome

Timeframe: From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)

Population: ITT Population

Clinical benefit response is defined as the number of participants with evidence of complete (CR) or partial (PR) tumor response or stable disease (SD) for at least 6 months (183 days). Per Response Evaluation Criteria In Solid Tumors (RECIST): CR, all detectable tumor has disappeared; PR, a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum; Stable Disease, small changes that do not meet previously given criteria. Confirmation requires at least 2 assessments of CR/PR with at least 4 weeks between assessments.

Outcome measures

Outcome measures
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg n=78 Participants Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy n=74 Participants 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy 800 mg (2 x 400 mg tablets) of oral pazopanib daily
Clinical Benefit Response	7 participants	15 participants	—

SECONDARY outcome

Timeframe: From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)

Population: ITT Population

Response is defined as the number of participants achieving either a complete or partial tumor response per RECIST criteria. CR, all detectable tumor has disappeared; PR, a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum.

Outcome measures

Outcome measures
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg n=78 Participants Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy n=74 Participants 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy 800 mg (2 x 400 mg tablets) of oral pazopanib daily
Response	4 participants	7 participants	—

SECONDARY outcome

Timeframe: From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)

Population: ITT Population

For the subset of participants who showed a confirmed CR or PR, time to response was defined as the time from randomization until the first documented evidence of CR or PR (whichever status was recorded first). CR, all detectable tumor has disappeared; PR, a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum.

Outcome measures

Outcome measures
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg n=4 Participants Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy n=7 Participants 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy 800 mg (2 x 400 mg tablets) of oral pazopanib daily
Time to Response	18.2 weeks Interval 6.0 to 24.1	6.9 weeks Interval 5.6 to 11.9	—

SECONDARY outcome

Timeframe: From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)

Population: ITT Population. The median for lapatinib was not reached at the time of data cut-off. No formal analysis of this endpoint was conducted for this group due to a very small number of responding participants.

For participants who had a CR or PR, the duration of response was defined as the time from first documented evidence of PR or CR until the first documented sign of disease progression or death. CR, all detectable tumor has disappeared; PR, a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum.

Outcome measures

Outcome measures
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy n=7 Participants 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy 800 mg (2 x 400 mg tablets) of oral pazopanib daily
Duration of Response	—	48.1 weeks Interval 12.0 to 48.1	—

SECONDARY outcome

Timeframe: From Randomization (11 December 2006) until last participant had last visit (28 July 2011) in combined population of two monotherapy arms (up to 241.43 weeks)

Population: Safety Population: all participants who received at least one dose of study drug

Safety was assessed as the number of participants experiencing a serious adverse event (SAE) or an adverse event (AE). See the adverse event module for safety data.

Outcome measures

Outcome measures
Measure	Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg n=76 Participants Lapatinib 1500 mg (6 x 250 mg tablets) and pazopanib 800 mg (2 x 400 mg tablets) daily	Lapatinib Monotherapy n=74 Participants 1500 mg (6 x 250 mg tablets) of oral lapatinib daily	Pazopanib Monotherapy n=76 Participants 800 mg (2 x 400 mg tablets) of oral pazopanib daily
Safety and Tolerability of Pazopanib, Lapatinib and the Combination of Pazopanib and Lapatinib Serious adverse events	22 participants	28 participants	32 participants
Safety and Tolerability of Pazopanib, Lapatinib and the Combination of Pazopanib and Lapatinib Other adverse events with >5% occurrence	66 participants	69 participants	71 participants

Adverse Events

Combination Therapy: Lapatinib 1500 mg and Pazopanib 800 mg

Serious events: 32 serious events

Other events: 71 other events

Deaths: 0 deaths

Lapatinib Monotherapy

Serious events: 22 serious events

Other events: 66 other events

Deaths: 0 deaths

Pazopanib Monotherapy

Serious events: 28 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER