E7050 in Combination With Cetuximab Versus Cetuximab Alone in the Treatment of Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck
Sponsor
Eisai Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01332266
Collaborator
PharmaBio Development Inc. (Industry)
95
23
2
71.5
4.1
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether participants with platinum-resistant squamous cell carcinoma of the head and neck (SCCHN) who receive either E7050 administered with cetuximab or cetuximab alone experience greater benefit.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
This open-label, multicenter, randomized study will consist of a Phase 1b: a safety run-in period with 3 ascending doses of E7050 in combination with cetuximab; and a Phase 2 portion: a randomized 2-arm period. Approximately 95 participants with platinum-resistant squamous cell carcinoma of the head and neck will be enrolled in the study (10-15 participants in the Phase 1b portion and 80 participants in the Phase 2 portion). Participants will only participate in either the Phase 1b or the Phase 2 portion of the study.
In the Phase 2 portion, participants will receive study treatment (E7050 plus cetuximab or cetuximab alone) for approximately six 28-day cycles (24 weeks). Beyond 24 weeks, participants who are experiencing clinical benefit may continue E7050 plus cetuximab, cetuximab alone or E7050 alone (Arm 1), or may continue cetuximab alone (Arm 2), depending on the original randomization treatment arm, for as long as clinical benefit is sustained and the treatment is well tolerated.
Study Design
Study Type:
Interventional
Actual Enrollment
:
95 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Multicenter, Randomized, Phase 1b/2 Study of E7050 in Combination With Cetuximab Versus Cetuximab Alone in the Treatment of Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck
Actual Study Start Date
:
Sep 19, 2011
Actual Primary Completion Date
:
Jan 31, 2016
Actual Study Completion Date
:
Sep 4, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Active Comparator; Phase 1b: Cohort 1,2,and 3 Phase 1b: Cohort 1; 200 mg E7050 + 250 mg/m2 cetuximab Cohort 2; 300 mg E7050 + 250 mg/m2 cetuximab Cohort 3; 400mg E7050 + 250mg/m2 cetuximab Phase 2: Arm 1; MTD E7050 + 250 mg cetuximab Arm 2; 250 mg cetuximab Interventions: Drug cetuximab |
Drug: E7050
E7050 given orally at 200, 300, or 400 mg once daily.
Other Names:
Drug: Cetuximab
Cetuximab is given at an initial dose of 400 mg/m2 given as a 2-hour intravenous (IV) infusion on Day 1 of Cycle 1, followed by a dose of 250 mg/m2 given as a 1-hour IV infusion on Day 8, Day 15, and Day 22 of Cycle 1, and Day 1, Day 8, Day 15, and Day 22 of each subsequent cycle.
|
| Active Comparator: Phase 2 Phase 2: Arm 1; MTD E7050 + 250 mg/m2 cetuximab Arm 2; 250 mg/m2 cetuximab |
Drug: E7050
E7050 given orally at 200, 300, or 400 mg once daily.
Other Names:
Drug: Cetuximab
Cetuximab is given at an initial dose of 400 mg/m2 given as a 2-hour intravenous (IV) infusion on Day 1 of Cycle 1, followed by a dose of 250 mg/m2 given as a 1-hour IV infusion on Day 8, Day 15, and Day 22 of Cycle 1, and Day 1, Day 8, Day 15, and Day 22 of each subsequent cycle.
|
Outcome Measures
Primary Outcome Measures
- Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0) [Cycle 1 (Cycle length is equal to [=] 28 days)]
DLT:adverse events graded as NCI CTCAEv4.0 occurring less than or equal to(<=)28 days after treatment.Events as: Non-hematological: 1)Grade greater than or equal to(>=)3 peripheral neuropathy; 2)Grade 3 fatigue or 2 point decline in eastern cooperative oncology group performance status that persisted for greater than(>)7 days; 3)Grade >=3 nausea,vomiting despite optimal antiemetic treatment; 4)Any nonhematologic toxicity of Grade >=3, with exceptions as alopecia,single laboratory values out of normal range,hypersensitivity reaction. Hematological 1)Grade 4 neutropenia lasting >7 days; 2)Febrile neutropenia as fever >=38.5 degree celsius with absolute neutrophil count less than(<)1.0*10^9 per liter(/L); 3)Grade 3 thrombocytopenia with nontraumatic bleeding requiring platelet transfusion; 4)Grade 4 thrombocytopenia with/without nontraumatic bleeding. Other 1)Study drug related death; 2)Toxicity that dose escalation committee believed to be DLT that was not covered by above DLT criteria.
- Phase 1b: Plasma Concentration of Golvatinib When Given in Combination With Cetuximab [Cycle 1: 0-48 hours post-dose (Each cycle=28 days)]
- Phase 2: Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) [Up to 5 years 11 months]
TEAEs are defined as an adverse event that has an onset date, or a worsening in severity from baseline (pre-golvatinib), on or after the first dose of golvatinib. The severity was graded according to CTCAE v4.0. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event.
- Phase 2: Number of Participants With Markedly Abnormal Vital Sign Values [Up to 4 years 4 months]
- Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings [Up to 4 years 4 months]
Physical examination was performed and included evaluation of 1) General appearance, 2) Head; Eyes; Ears; Nose; Throat (HEENT), 3) Neck, 4) Heart, 5) Chest (Including Lungs), 6) Abdomen, 7) Extremities, 8) Skin, 9) Lymph Nodes, and 10) neurological status. Here, number of participants with markedly abnormal physical examinations were reported.
- Phase 2: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values [Up to 4 years 4 months]
Secondary Outcome Measures
- Phase 2: Progression-free Survival (PFS) [From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 4 years 4 months)]
PFS is defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on response evaluation criteria in solid tumor (RECIST) v1.1. PD is defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.
- Phase 2: Percentage of Participants With PFS at Week 12 [At Week 12]
PFS rate at week 12 is defined as the percentage of participants who were still alive without disease progression at 12 weeks from the date of randomization. PFS is defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on RECIST v1.1. PD is defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS rate was estimated and analyzed using Kaplan Meier method.
- Phase 2: Time to Progression (TTP) [From the date of randomization until the date of PD (Up to approximately 4 years 4 months)]
TTP is defined as the time from the date of randomization until the date of PD based on RECIST v1.1. PD is defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. TTP was estimated and analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.
- Phase 2: Overall Survival (OS) [From the date of randomization until the date of death (Up to approximately 4 years 4 months)]
OS is defined as the time from the date of randomization until the date of death. OS was analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.
- Phase 2: Percentage of Participants With Overall Response [From the date of randomization until CR or PR (Up to approximately 4 years 4 months)]
Overall response rate is defined as percentage of participants with complete response (CR) or partial response (PR) based on RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As planned, data for this endpoint was analyzed and collected till primary completion date.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Platinum-resistant (defined as failure to respond to treatment with a platinum agent or recurrence of disease after initial response to platinum within 12 months of completing therapy), locally advanced, recurrent and/or metastatic SCCHN, which is untreatable by surgical resection or radiation therapy
-
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
-
Blood pressure must be well-controlled. Participants must have no history of hypertensive crisis or hypertensive encephalopathy; Adequate end organ function
Exclusion Criteria
-
Nasopharyngeal tumors
-
Previously received E7050, anti-angiogenic therapy, or anti-epidermal growth factor receptor (EGFR) therapy (prior anti-angiogenic/EGFR therapy is permitted in Phase 1b only. Prior cetuximab is permitted if administered in combination with radiation
-
Presence of brain metastases, unless the participant has received adequate treatment at least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids for at least 4 weeks prior to randomization
-
Palliative radiotherapy is not permitted throughout the study period
-
Clinically significant hemoptysis
-
Serious non-healing wound, ulcer, or active bone fracture
-
Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for a major surgical procedure during the course of the study
-
Clinically significant gastrointestinal bleeding within 6 months prior to first dose.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tucson | Arizona | United States | 85715 | |
| 2 | Fort Myers | Florida | United States | 33905 | |
| 3 | Boston | Massachusetts | United States | 02111 | |
| 4 | Saint Louis | Missouri | United States | 63110 | |
| 5 | Toledo | Ohio | United States | 43623 | |
| 6 | Oklahoma City | Oklahoma | United States | 73104 | |
| 7 | Nashville | Tennessee | United States | 37203 | |
| 8 | Goyang-si | Gyeonggi-do | Korea, Republic of | 410-769 | |
| 9 | Hwasun | Jeollanam-do | Korea, Republic of | 519-763 | |
| 10 | Busan | Korea, Republic of | 602-739 | ||
| 11 | Seoul | Korea, Republic of | 110-744 | ||
| 12 | Seoul | Korea, Republic of | 120-752 | ||
| 13 | Seoul | Korea, Republic of | 135-710 | ||
| 14 | Seoul | Korea, Republic of | 138-736 | ||
| 15 | Dnipropetrovsk | Ukraine | 49102 | ||
| 16 | Donetsk | Ukraine | 83003 | ||
| 17 | Donetsk | Ukraine | 83092 | ||
| 18 | Kharkiv | Ukraine | 61024 | ||
| 19 | Kyiv | Ukraine | 3057 | ||
| 20 | Sumy | Ukraine | 40005 | ||
| 21 | London | Greater London | United Kingdom | NW1 2BU | |
| 22 | Manchester | Greater Manchester | United Kingdom | M20 4BX | |
| 23 | Glasgow | Strathclyde | United Kingdom | G12 0YN |
Sponsors and Collaborators
- Eisai Inc.
- PharmaBio Development Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01332266
Other Study ID Numbers:
- E7050-702
- 2011-000773-31
First Posted:
Apr 11, 2011
Last Update Posted:
Jan 3, 2022
Last Verified:
Dec 1, 2017
Studies a U.S. FDA-regulated Drug Product:
Yes
Keywords provided by Eisai Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 28 investigative sites in the Republic of Korea, Ukraine, United Kingdom, and the United States from 19 September 2011 to 04 September 2017. |
|---|---|
| Pre-assignment Detail | This study consists of two phases Phase 1b and Phase 2. Phase 1b: 12 participants were enrolled and received the study treatment; Phase 2: 83 participants were enrolled and received the study treatment. |
| Arm/Group Title | Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with platinum-resistant squamous cell carcinoma of the head and neck (SCCHN) received golvatinib 200 milligram (mg) tablets, orally, once daily (run-in period) and cetuximab 400 milligram per square meter (mg/m^2) intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining maximum tolerated dose (MTD) or Recommended Phase 2 dose (RP2D), until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received golvatinib 300 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received golvatinib 400 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Period Title: Phase 1b | |||||
| STARTED | 4 | 5 | 3 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 4 | 5 | 3 | 0 | 0 |
| Period Title: Phase 1b | |||||
| STARTED | 0 | 0 | 0 | 42 | 41 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 42 | 41 |
Baseline Characteristics
| Arm/Group Title | Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 200 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received golvatinib 300 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received golvatinib 400 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Total of all reporting groups |
| Overall Participants | 4 | 5 | 3 | 42 | 41 | 95 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
70.0
(8.29)
|
58.8
(12.58)
|
59.3
(5.51)
|
58.4
(11.04)
|
53.9
(9.84)
|
57.0
(10.79)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
2
50%
|
0
0%
|
0
0%
|
4
9.5%
|
7
17.1%
|
13
13.7%
|
| Male |
2
50%
|
5
100%
|
3
100%
|
38
90.5%
|
34
82.9%
|
82
86.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
1
25%
|
0
0%
|
0
0%
|
1
2.4%
|
0
0%
|
2
2.1%
|
| Not Hispanic or Latino |
3
75%
|
5
100%
|
3
100%
|
41
97.6%
|
41
100%
|
93
97.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
2
50%
|
3
60%
|
3
100%
|
16
38.1%
|
12
29.3%
|
36
37.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
20%
|
0
0%
|
1
2.4%
|
0
0%
|
2
2.1%
|
| White |
2
50%
|
1
20%
|
0
0%
|
24
57.1%
|
29
70.7%
|
56
58.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
0
0%
|
1
1.1%
|
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) (Count of Participants) | ||||||
| ECOG: 0 (Fully Active) |
1
25%
|
0
0%
|
0
0%
|
10
23.8%
|
10
24.4%
|
21
22.1%
|
| ECOG: 1 (Restricted in Physical Activity; Ambulatory) |
3
75%
|
4
80%
|
3
100%
|
28
66.7%
|
24
58.5%
|
62
65.3%
|
| ECOG: 2 (Ambulatory and Capable of All Self-care) |
0
0%
|
1
20%
|
0
0%
|
1
2.4%
|
3
7.3%
|
5
5.3%
|
| ECOG: 3 (Capable of Only Limited Self-care) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ECOG: 4 (Completely Disabled) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ECOG: 5 (Dead) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Specified |
0
0%
|
0
0%
|
0
0%
|
3
7.1%
|
4
9.8%
|
7
7.4%
|
Outcome Measures
| Title | Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0) |
|---|---|
| Description | DLT:adverse events graded as NCI CTCAEv4.0 occurring less than or equal to(<=)28 days after treatment.Events as: Non-hematological: 1)Grade greater than or equal to(>=)3 peripheral neuropathy; 2)Grade 3 fatigue or 2 point decline in eastern cooperative oncology group performance status that persisted for greater than(>)7 days; 3)Grade >=3 nausea,vomiting despite optimal antiemetic treatment; 4)Any nonhematologic toxicity of Grade >=3, with exceptions as alopecia,single laboratory values out of normal range,hypersensitivity reaction. Hematological 1)Grade 4 neutropenia lasting >7 days; 2)Febrile neutropenia as fever >=38.5 degree celsius with absolute neutrophil count less than(<)1.0*10^9 per liter(/L); 3)Grade 3 thrombocytopenia with nontraumatic bleeding requiring platelet transfusion; 4)Grade 4 thrombocytopenia with/without nontraumatic bleeding. Other 1)Study drug related death; 2)Toxicity that dose escalation committee believed to be DLT that was not covered by above DLT criteria. |
| Time Frame | Cycle 1 (Cycle length is equal to [=] 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment. |
| Arm/Group Title | Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received 200 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received 300 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 4 | 5 | 3 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Phase 1b: Plasma Concentration of Golvatinib When Given in Combination With Cetuximab |
|---|---|
| Description | |
| Time Frame | Cycle 1: 0-48 hours post-dose (Each cycle=28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not collected and analyzed for this outcome measure because no pharmacokinetic analysis was conducted in this study due to incomplete pharmacokinetic sample bioanalysis due to unresolved queries leading to inadequate calculations and limited data interpretability. |
| Arm/Group Title | Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received 200 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received 300 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 0 | 0 | 0 |
| Title | Phase 2: Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) |
|---|---|
| Description | TEAEs are defined as an adverse event that has an onset date, or a worsening in severity from baseline (pre-golvatinib), on or after the first dose of golvatinib. The severity was graded according to CTCAE v4.0. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event. |
| Time Frame | Up to 5 years 11 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment. |
| Arm/Group Title | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 |
|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 42 | 41 |
| Count of Participants [Participants] |
21
525%
|
21
420%
|
| Title | Phase 2: Number of Participants With Markedly Abnormal Vital Sign Values |
|---|---|
| Description | |
| Time Frame | Up to 4 years 4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment. |
| Arm/Group Title | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 |
|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 42 | 41 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings |
|---|---|
| Description | Physical examination was performed and included evaluation of 1) General appearance, 2) Head; Eyes; Ears; Nose; Throat (HEENT), 3) Neck, 4) Heart, 5) Chest (Including Lungs), 6) Abdomen, 7) Extremities, 8) Skin, 9) Lymph Nodes, and 10) neurological status. Here, number of participants with markedly abnormal physical examinations were reported. |
| Time Frame | Up to 4 years 4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment. |
| Arm/Group Title | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 |
|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 42 | 41 |
| General Appearance |
5
125%
|
6
120%
|
| HEENT |
20
500%
|
17
340%
|
| Neck |
24
600%
|
22
440%
|
| Heart |
1
25%
|
0
0%
|
| Chest (Including Lungs) |
4
100%
|
5
100%
|
| Abdomen |
6
150%
|
3
60%
|
| Extremities |
2
50%
|
0
0%
|
| Skin |
4
100%
|
5
100%
|
| Lymph Nodes |
13
325%
|
15
300%
|
| Neurologic |
3
75%
|
5
100%
|
| Title | Phase 2: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values |
|---|---|
| Description | |
| Time Frame | Up to 4 years 4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment. |
| Arm/Group Title | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 |
|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 42 | 41 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Phase 2: Progression-free Survival (PFS) |
|---|---|
| Description | PFS is defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on response evaluation criteria in solid tumor (RECIST) v1.1. PD is defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date. |
| Time Frame | From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 4 years 4 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent-to-Treat (MITT) analysis set included all participants randomized in the applicable study arm who received any comparator or study drug. |
| Arm/Group Title | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 |
|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 42 | 41 |
| Median (95% Confidence Interval) [weeks] |
15.71
|
15.71
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2, Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.89 | |
| Confidence Interval |
(2-Sided) 95% 0.54 to 1.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Phase 2: Percentage of Participants With PFS at Week 12 |
|---|---|
| Description | PFS rate at week 12 is defined as the percentage of participants who were still alive without disease progression at 12 weeks from the date of randomization. PFS is defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on RECIST v1.1. PD is defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS rate was estimated and analyzed using Kaplan Meier method. |
| Time Frame | At Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT analysis set included all participants randomized in the applicable study arm who received any comparator or study drug. |
| Arm/Group Title | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 |
|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 42 | 41 |
| Number (95% Confidence Interval) [percentage of participants] |
68.9
1722.5%
|
59.4
1188%
|
| Title | Phase 2: Time to Progression (TTP) |
|---|---|
| Description | TTP is defined as the time from the date of randomization until the date of PD based on RECIST v1.1. PD is defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. TTP was estimated and analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date. |
| Time Frame | From the date of randomization until the date of PD (Up to approximately 4 years 4 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT analysis set included all participants randomized in the applicable study arm who received any comparator or study drug. |
| Arm/Group Title | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 |
|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 42 | 41 |
| Median (95% Confidence Interval) [weeks] |
15.43
|
16.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2, Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 95% 0.61 to 1.73 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Phase 2: Overall Survival (OS) |
|---|---|
| Description | OS is defined as the time from the date of randomization until the date of death. OS was analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date. |
| Time Frame | From the date of randomization until the date of death (Up to approximately 4 years 4 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT analysis set included all participants randomized in the applicable study arm who received any comparator or study drug. Here "Overall number of participants analyzed" signifies participants with events (death). |
| Arm/Group Title | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 |
|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 33 | 36 |
| Median (95% Confidence Interval) [weeks] |
39.71
|
36.71
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2, Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.85 | |
| Confidence Interval |
(2-Sided) 95% 0.53 to 1.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Phase 2: Percentage of Participants With Overall Response |
|---|---|
| Description | Overall response rate is defined as percentage of participants with complete response (CR) or partial response (PR) based on RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As planned, data for this endpoint was analyzed and collected till primary completion date. |
| Time Frame | From the date of randomization until CR or PR (Up to approximately 4 years 4 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT analysis set included all participants randomized in the applicable study arm who received any comparator or study drug. |
| Arm/Group Title | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 |
|---|---|---|
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant squamous cell carcinoma of the head and neck received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After six cycles, at the discretion of the Investigator, participants experienced clinical benefit have continued for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. |
| Measure Participants | 42 | 41 |
| Number (95% Confidence Interval) [percentage of participants] |
9.5
237.5%
|
4.9
98%
|
Adverse Events
| Time Frame | Up to 5 years 11 months | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 | |||||
| Arm/Group Description | Participants with platinum-resistant SCCHN received golvatinib 200 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received golvatinib 300 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received golvatinib 400 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | Participants with platinum-resistant SCCHN received cetuximab 400 mg/m^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first. | |||||
All Cause Mortality |
||||||||||
| Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/4 (75%) | 3/5 (60%) | 2/3 (66.7%) | 33/42 (78.6%) | 36/41 (87.8%) | |||||
Serious Adverse Events |
||||||||||
| Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/4 (25%) | 4/5 (80%) | 2/3 (66.7%) | 15/42 (35.7%) | 15/41 (36.6%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 3/41 (7.3%) | 3 |
| Cardiac disorders | ||||||||||
| Pericardial Effusion | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Gastrointestinal disorders | ||||||||||
| Abdominal Pain | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Nausea | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| Vomiting | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Dysphagia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 2/42 (4.8%) | 2 | 1/41 (2.4%) | 1 |
| Haematemesis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Mechanical Ileus | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| Oral Cavity Fistula | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Rectal Haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| General disorders | ||||||||||
| Adverse Drug Reaction | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Infections and infestations | ||||||||||
| Cellulitis | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Pneumonia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 3/42 (7.1%) | 3 | 1/41 (2.4%) | 1 |
| Pyelonephritis Acute | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Staphylococcal Infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| Tuberculosis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| Upper Respiratory Tract Infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||
| Alcohol Poisoning | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| Post Procedural Haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Fistula | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Neck Pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| Pain In Jaw | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| Back Pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Tumour Haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 2/41 (4.9%) | 3 |
| Nervous system disorders | ||||||||||
| Depressed Level Of Consciousness | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Presyncope | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Dyspnoea | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 1/41 (2.4%) | 1 |
| Pneumonia Aspiration | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 2/42 (4.8%) | 2 | 0/41 (0%) | 0 |
| Upper Airway Obstruction | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Asphyxia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Aspiration | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| Oropharyngeal Pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 1/41 (2.4%) | 1 |
| Pulmonary Embolism | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 0/41 (0%) | 0 |
| Stridor | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 1/41 (2.4%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Haemorrhage Subcutaneous | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Vascular disorders | ||||||||||
| Deep Vein Thrombosis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Haemorrhage | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
| Hypotension | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 1/41 (2.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2 | Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2 | Phase 2: Arm 2: Cetuximab 400 mg/m^2 | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 5/5 (100%) | 3/3 (100%) | 42/42 (100%) | 38/41 (92.7%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 2/4 (50%) | 4 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 4/42 (9.5%) | 5 | 5/41 (12.2%) | 6 |
| Ear and labyrinth disorders | ||||||||||
| Otorrhoea | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Eye disorders | ||||||||||
| Blepharitis | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Eyelid oedema | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Ocular hyperaemia | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Pinguecula | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Abdominal Pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 4/42 (9.5%) | 8 | 1/41 (2.4%) | 1 |
| Abdominal Pain Upper | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 3/42 (7.1%) | 3 | 1/41 (2.4%) | 1 |
| Nausea | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 1/3 (33.3%) | 2 | 19/42 (45.2%) | 35 | 3/41 (7.3%) | 3 |
| Constipation | 1/4 (25%) | 2 | 1/5 (20%) | 1 | 2/3 (66.7%) | 2 | 10/42 (23.8%) | 13 | 3/41 (7.3%) | 3 |
| Diarrhoea | 2/4 (50%) | 2 | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 10/42 (23.8%) | 22 | 4/41 (9.8%) | 4 |
| Dyspepsia | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Dysphagia | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 5/42 (11.9%) | 6 | 2/41 (4.9%) | 2 |
| Haemorrhoids | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Oral Pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 4 | 0/41 (0%) | 0 |
| Stomatitis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 3 | 2/41 (4.9%) | 3 |
| Vomiting | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 14/42 (33.3%) | 19 | 2/41 (4.9%) | 2 |
| Anal pruritus | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Oesophageal ulcer | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| General disorders | ||||||||||
| Asthenia | 1/4 (25%) | 1 | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 5/42 (11.9%) | 5 | 1/41 (2.4%) | 1 |
| Chest Pain | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 3 | 1/41 (2.4%) | 1 |
| Face Oedema | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Fatigue | 1/4 (25%) | 2 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 5/42 (11.9%) | 5 | 5/41 (12.2%) | 5 |
| Localised Oedema | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Oedema Peripheral | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Pyrexia | 1/4 (25%) | 2 | 2/5 (40%) | 2 | 1/3 (33.3%) | 1 | 3/42 (7.1%) | 3 | 1/41 (2.4%) | 2 |
| Mucosal Inflammation | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 4/42 (9.5%) | 6 | 1/41 (2.4%) | 1 |
| Infections and infestations | ||||||||||
| Paronychia | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 4/42 (9.5%) | 10 | 0/41 (0%) | 0 |
| Upper Respiratory Tract Infection | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Lower Respiratory Tract Infection | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 3 | 1/41 (2.4%) | 1 |
| Candida infection | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Hip fracture | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Investigations | ||||||||||
| Alanine Aminotransferase Increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 2/3 (66.7%) | 9 | 10/42 (23.8%) | 12 | 3/41 (7.3%) | 3 |
| Blood Alkaline Phosphatase Increased | 0/4 (0%) | 0 | 3/5 (60%) | 4 | 0/3 (0%) | 0 | 3/42 (7.1%) | 4 | 0/41 (0%) | 0 |
| Blood Lactate Dehydrogenase Increased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 3 | 0/41 (0%) | 0 |
| Aspartate Aminotransferase Increased | 0/4 (0%) | 0 | 1/5 (20%) | 3 | 2/3 (66.7%) | 2 | 10/42 (23.8%) | 10 | 2/41 (4.9%) | 3 |
| Neutrophil Count Decreased | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 1/3 (33.3%) | 3 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Weight Decreased | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 6/42 (14.3%) | 6 | 3/41 (7.3%) | 3 |
| Eastern Cooperative Oncology Group Performance Status Worsened | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 3/41 (7.3%) | 3 |
| Metabolism and nutrition disorders | ||||||||||
| Decreased Appetite | 2/4 (50%) | 2 | 2/5 (40%) | 2 | 1/3 (33.3%) | 1 | 10/42 (23.8%) | 12 | 3/41 (7.3%) | 3 |
| Hypercalcaemia | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Hyperglycaemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Hypoalbuminaemia | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Hypocalcaemia | 2/4 (50%) | 2 | 2/5 (40%) | 2 | 1/3 (33.3%) | 2 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Hypokalaemia | 1/4 (25%) | 1 | 2/5 (40%) | 2 | 0/3 (0%) | 0 | 3/42 (7.1%) | 4 | 2/41 (4.9%) | 2 |
| Hypomagnesaemia | 2/4 (50%) | 3 | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 2/42 (4.8%) | 3 | 3/41 (7.3%) | 5 |
| Hyponatraemia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Hypophosphataemia | 2/4 (50%) | 2 | 0/5 (0%) | 0 | 2/3 (66.7%) | 6 | 3/42 (7.1%) | 3 | 1/41 (2.4%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Muscle Spasms | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Muscular Weakness | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Musculoskeletal Chest Pain | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Pain in Extremity | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 4 | 1/41 (2.4%) | 1 |
| Neck Pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 3/42 (7.1%) | 3 | 2/41 (4.9%) | 2 |
| Back Pain | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Periarthritis | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Arthralgia | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Tumour Pain | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 4 | 2/41 (4.9%) | 2 |
| Nervous system disorders | ||||||||||
| Dizziness | 1/4 (25%) | 1 | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Dysgeusia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 3/42 (7.1%) | 3 | 0/41 (0%) | 0 |
| Lethargy | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 4 | 1/41 (2.4%) | 2 |
| Peripheral sensory neuropathy | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Psychiatric disorders | ||||||||||
| Insomnia | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/42 (2.4%) | 1 | 3/41 (7.3%) | 3 |
| Depression | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 3 | 1/41 (2.4%) | 1 |
| Substance-induced psychotic disorder | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Renal and urinary disorders | ||||||||||
| Dysuria | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Haematuria | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 3/42 (7.1%) | 4 | 1/41 (2.4%) | 1 |
| Pollakiuria | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Proteinuria | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 6/42 (14.3%) | 7 | 2/41 (4.9%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 3/42 (7.1%) | 3 | 2/41 (4.9%) | 2 |
| Dyspnoea | 3/4 (75%) | 4 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 3/41 (7.3%) | 3 |
| Epistaxis | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 3 | 0/41 (0%) | 0 |
| Haemoptysis | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 2/42 (4.8%) | 2 | 3/41 (7.3%) | 3 |
| Nasal Ulcer | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Oropharyngeal Pain | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 2/3 (66.7%) | 3 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Productive Cough | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Dermatitis Acneiform | 3/4 (75%) | 6 | 0/5 (0%) | 0 | 2/3 (66.7%) | 3 | 10/42 (23.8%) | 17 | 7/41 (17.1%) | 9 |
| Erythema | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Pruritus | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Rash | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 2/3 (66.7%) | 3 | 19/42 (45.2%) | 22 | 8/41 (19.5%) | 9 |
| Skin Fissures | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 4/42 (9.5%) | 5 | 0/41 (0%) | 0 |
| Skin Ulcer | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Dry Skin | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 5/42 (11.9%) | 7 | 1/41 (2.4%) | 1 |
| Rash Maculo-Papular | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 4/42 (9.5%) | 5 | 5/41 (12.2%) | 12 |
| Palmar-Plantar Erythrodysaesthesia Syndrome | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 3/42 (7.1%) | 4 | 2/41 (4.9%) | 2 |
| Onychomadesis | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/42 (2.4%) | 1 | 3/41 (7.3%) | 3 |
| Vascular disorders | ||||||||||
| Flushing | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
| Hypertension | 1/4 (25%) | 3 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/42 (0%) | 0 | 0/41 (0%) | 0 |
Limitations/Caveats
No pharmacokinetic analysis was conducted in this study due to incomplete pharmacokinetic sample bioanalysis due to unresolved queries leading to inadequate calculations and limited data interpretability.
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.
Results Point of Contact
| Name/Title | Eisai Medical Information |
|---|---|
| Organization | Eisai Inc. |
| Phone | +1-888-274-2378 |
| esi_oncmedinfo@eisai.com |
Responsible Party:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01332266
Other Study ID Numbers:
- E7050-702
- 2011-000773-31
First Posted:
Apr 11, 2011
Last Update Posted:
Jan 3, 2022
Last Verified:
Dec 1, 2017