Axitinib For The Treatment Of Advanced Hepatocellular Carcinoma - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Participant, Investigator; Primary Purpose: Treatment
Condition:	Hepatocellular Carcinoma
Interventions:	Drug: Axitinib (AG-013736) Other: Best Supportive Care Drug: Placebo

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Total 224 participants were enrolled in the study. Randomized portion enrolled 202 participants in 2 arms (134 in axitinib, 68 in placebo) in 70 centers (13 countries). Non-randomized portion enrolled 22 participants in 2 cohorts (15 in Child-Pugh class A, 7 in Child-Pugh Class B score 7) according to Child-Pugh score in 13 centers (4 countries).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with Child-Pugh Class A (score 5 or 6) could have been enrolled into either non-randomized or to randomized portion. Participants with Child-Pugh Class B (score 7) were initially enrolled into non-randomized portion but following determination of recommended axitinib starting dose they could have been enrolled in randomized portion.

Reporting Groups

	Description
Child-Pugh Class A	Participants with Child-Pugh Class A disease (score 5 or 6) were enrolled into the non-randomized portion at selected sites only at a starting axitinib dose of 5 mg twice daily (BID).
Child-Pugh Class B	Participants with Child-Pugh Class B disease (score 7) at selected sites were initially enrolled only into the non-randomized portion of this study to determine the recommended starting dose of axitinib for this population. The initial starting dose for this group was 2 mg BID.
Axitinib	Participants in this group received axitinib + best supportive care. Participants with Child-Pugh Class A disease (score 5 or 6) were enrolled into the randomized portion at a starting axitinib dose of 5 mg BID orally. Participants with Child-Pugh Class B disease (score 7) were to begin enrollment into the randomized portion of the study following determination of the recommended axitinib starting dose in the non-randomized portion. Study treatment was administered in cycles of 4 weeks in duration.
Placebo	Participants in this group received placebo + best supportive care. Treatment was administered in cycles of 4 weeks in duration. The starting dose of placebo for participants with Child Pugh Class A disease (score 5 or 6) was chosen as 5 mg BID. Participants with Child-Pugh Class B, score 7 received placebo that was determined from the non-randomized portion of the study until the recommended starting dose was determined, participants with Child-Pugh Class B, score 7, were not permitted to enter the randomized portion of the study.

Participant Flow: Overall Study

	Child-Pugh Class A	Child-Pugh Class B	Axitinib	Placebo
STARTED	15	7	134	68
COMPLETED	0	0	0	0
NOT COMPLETED	15	7	134	68
Participant Refused Further Follow-Up	1	0	11	2
Death	14	6	101	52
Ongoing in Follow-up	0	1	14	13
Ongoing on Treatment	0	0	7	1
Lost to Follow-up	0	0	1	0

Baseline Characteristics

Hide Baseline Characteristics

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Child-Pugh Class A	Participants with Child-Pugh Class A disease (score 5 or 6) were enrolled into the non-randomized portion at selected sites only at a starting axitinib dose of 5 mg BID.
Child-Pugh Class B	Participants with Child-Pugh Class B disease (score 7) at selected sites were initially enrolled only into the non-randomized portion of this study to determine the recommended starting dose of axitinib for this population. The initial starting dose for this group was 2 mg BID.
Axitinib	Participants in this group received axitinib + best supportive care. Participants with Child-Pugh Class A disease (score 5 or 6) were enrolled into the randomized portion at a starting axitinib dose of 5 mg BID orally. Participants with Child-Pugh Class B disease (score 7) were to begin enrollment into the randomized portion of the study following determination of the recommended axitinib starting dose in the non randomized portion. Study treatment was administered in cycles of 4 weeks in duration.
Placebo	Participants in this group received placebo + best supportive care. Treatment was administered in cycles of 4 weeks in duration. The starting dose of placebo for participants with Child Pugh Class A disease (score 5 or 6) was chosen as 5 mg BID. Participants with Child-Pugh Class B, score 7 received placebo that was determined from the non-randomized portion of the study until the recommended starting dose was determined, participants with Child Pugh Class B, score 7, were not permitted to enter the randomized portion of the study.
Total	Total of all reporting groups

Baseline Measures

	Child-Pugh Class A	Child-Pugh Class B	Axitinib	Placebo	Total
Overall Participants Analyzed [Units: Participants]	15	7	134	68	224

Age, Customized [Units: Participants]
<18 years	0	0	0	0	0
18-44 years	4	0	7	4	15
45-64 years	5	5	74	32	116
>=65 years	6	2	53	32	93

Sex: Female, Male [Units: Participants] Count of Participants
Female	3 20.0%	2 28.6%	24 17.9%	12 17.6%	41 18.3%
Male	12 80.0%	5 71.4%	110 82.1%	56 82.4%	183 81.7%

Outcome Measures

Show All Outcome Measures

1. Primary:

Overall Survival (OS) - Stratified Analysis, Randomized Portion [ Time Frame: From randomization until at least two years after the last participant has been randomized ]

Show Outcome Measure 1

2. Secondary:

Progression-Free Survival (PFS) - Stratified Analysis, Randomized Portion [ Time Frame: Every 8 weeks until disease progression/death or start of new treatment or until at least two years after the last participant has been randomized, whatever occurs first ]

Show Outcome Measure 2

3. Secondary:

Objective Response Rate (ORR) - Percentage of Participants With Objective Response by Stratified Analysis, Randomized Portion. [ Time Frame: Every 8 weeks until at least two years after the last participant has been randomized ]

Show Outcome Measure 3

4. Secondary:

Time to Tumor Progression (TTP) - Stratified Analysis, Randomized Portion [ Time Frame: Every 8 weeks until disease progression/death or start of new treatment or until at least two years after the last participant has been randomized, whatever occurs first ]

Show Outcome Measure 4

5. Secondary:

Duration of Response (DR) by Unstratified Analysis, Randomized Portion [ Time Frame: From objective response to date of progression or death ]

Show Outcome Measure 5

6. Secondary:

Percentage of Participants With Overall Clinical Benefit Response (CBR) - Stratified Analysis, Randomized Portion [ Time Frame: From Baseline up to end of treatment ]

Show Outcome Measure 6

7. Secondary:

Axitinib Steady-state Pharmacokinetic (PK) Parameter - Maximum Observed Plasma Concentration (Cmax), Non-randomized Portion [ Time Frame: Cycle 1 Day 15 ]

Show Outcome Measure 7

8. Secondary:

Axitinib Steady-state PK Parameter - Area Under the Plasma Concentration Versus Time Curve From 0 to 24 hr (AUC0-24), Non-randomized Portion [ Time Frame: Cycle 1 Day 15 ]

Show Outcome Measure 8

9. Secondary:

Axitinib Steady-state Pharmacokinetic Parameter - Time to First Occurrence of Cmax (Tmax), Non-randomized Portion [ Time Frame: Cycle 1 Day 15 ]

Show Outcome Measure 9

10. Secondary:

Axitinib Steady-state Pharmacokinetic Parameter - Apparent Oral Clearance (CL/F), Non-randomized Portion [ Time Frame: Cycle 1 Day 15 ]

Show Outcome Measure 10

11. Secondary:

Axitinib Steady-state Pharmacokinetic Parameter - Terminal Plasma Elimination Half-life (t1/2), Non-randomized Portion [ Time Frame: Cycle 1 Day 15 ]

Show Outcome Measure 11

12. Secondary:

Axitinib Steady-state Pharmacokinetic Parameter - Apparent Oral Volume of Distribution of the Drug During the Elimination Phase (Vz/F), Non-randomized Portion [ Time Frame: Cycle 1 Day 15 ]

Show Outcome Measure 12

13. Secondary:

Concentration of Soluble Proteins at Baseline in Randomized Portion [ Time Frame: Baseline ]

Show Outcome Measure 13

14. Secondary:

Percentage of Participants With Specific miRNA Transcript Present in Circulation in Randomized Portion [ Time Frame: Baseline ]

Show Outcome Measure 14

15. Secondary:

Functional Assessment of Cancer Therapy – Hepatobiliary Questionnaire (FACT-Hep) in Randomized Portion: Overall Between-treatment Comparison Based on the Repeated Measures Mixed Effects Model [ Time Frame: Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date ]

Show Outcome Measure 15

16. Secondary:

Functional Assessment of Cancer Therapy - General (FACT-G) in Randomized Portion: Overall Between-treatment Comparison Based on the Repeated Measures Mixed Effects Model [ Time Frame: Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date ]

Show Outcome Measure 16

17. Secondary:

FHSI-8 in Randomized Portion: Overall Between-treatment Comparison Based on the Repeated Measures Mixed Effects Model [ Time Frame: Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date ]

Show Outcome Measure 17

18. Secondary:

FACT-G Subscales in Randomized Portion: Overall Between-treatment Comparison Based on the Repeated Measures Mixed Effects Model [ Time Frame: Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date ]

Show Outcome Measure 18

19. Secondary:

Functional Assessment of Cancer Therapy - Hepatobiliary Cancer Subscale (FACT Hep-CS18) Questionnaire in Randomized Portion: Overall Between-treatment Comparison Based on the Repeated Measures Mixed Effects Model [ Time Frame: Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date ]

Show Outcome Measure 19

20. Secondary:

Functional Assessment of Cancer Therapy - Hepatobiliary Cancer Trial Outcome Index (FACT Hep-TOI) Questionnaire in Randomized Portion: Overall Between-treatment Comparison Based on the Repeated Measures Mixed Effects Model [ Time Frame: Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date ]

Show Outcome Measure 20

21. Secondary:

Time to Deterioration (TTD) Based on the Composite Endpoint in Randomized Portion: Overall Between-treatment Comparison Based on the Repeated Measures Mixed Effects Model [ Time Frame: From randomization to death or tumor progression or FHSI-8 mean score decrease >=3 points, whichever comes first ]

Show Outcome Measure 21

22. Secondary:

EuroQoL (EQ-5D)- Health State Profile Utility Score in Randomized Portion: Overall Between-treatment Comparison Based on the Repeated Measures Mixed Effects Model [ Time Frame: Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date ]

Show Outcome Measure 22

23. Secondary:

EQ-VAS in Randomized Portion: Overall Between-treatment Comparison Based on the Repeated Measures Mixed Effects Model [ Time Frame: Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date ]

Show Outcome Measure 23

24. Secondary:

Number of Participants With Dose-limiting Toxicities (DLTs) in Non-randomized Portion [ Time Frame: Cycle 1 (4 weeks) ]

Show Outcome Measure 24

25. Secondary:

Number of Participants With Treatment-emergent AEs in Non-randomized Portion [ Time Frame: Up to 28 days after last dose of study drug, for up to 3 years ]

Show Outcome Measure 25

26. Secondary:

Number of Participants With Treatment-related AEs in Non-randomized Portion [ Time Frame: Up to 28 days after last dose of study drug, for up to 3 years ]

Show Outcome Measure 26

27. Secondary:

Number of Participants With Treatment-emergent Adverse Events (AEs) in Randomized Portion [ Time Frame: Up to 28 days after last dose of study drug, for up to 3 years ]

Show Outcome Measure 27

28. Secondary:

Number of Participants With Treatment-related AEs in Randomized Portion [ Time Frame: Up to 28 days after last dose of study drug, for up to 3 years ]

Show Outcome Measure 28

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

Limitations and Caveats

Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

More Information

Hide More Information

Certain Agreements:

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

There IS 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.

The agreement is:

	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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact:

Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kang YK, Yau T, Park JW, Lim HY, Lee TY, Obi S, Chan SL, Qin S, Kim RD, Casey M, Chen C, Bhattacharyya H, Williams JA, Valota O, Chakrabarti D, Kudo M. Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma. Ann Oncol. 2015 Dec;26(12):2457-63. doi: 10.1093/annonc/mdv388. Epub 2015 Sep 18.

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01210495 History of Changes
Other Study ID Numbers:	A4061058 2010-021590-37 ( EudraCT Number )
Study First Received:	September 22, 2010
Results First Received:	March 3, 2015
Last Updated:	February 8, 2017