Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations
Sponsor
Basilea Pharmaceutica (Industry)
Overall Status
Completed
CT.gov ID
NCT01752920
Collaborator
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.) (Industry)
119
12
4
68.6
9.9
0.1
Study Details
Study Description
Brief Summary
This was an open-label, Phase 1/2, dose escalation and signal finding study of derazantinib administered to patients with advanced solid tumors (Part 1; Dose Escalation/Food-effect Cohorts) or with advanced solid tumors with FGFR genetic aberrations, including iCCA with FGFR2 gene fusion (Part 2; Expanded Cohort, signal finding).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
119 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations, Including Intrahepatic Cholangiocarcinoma With FGFR2 Gene Fusion
Actual Study Start Date
:
Dec 10, 2012
Actual Primary Completion Date
:
Aug 28, 2018
Actual Study Completion Date
:
Aug 28, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Low Dose Group Patients who received derazantinib orally at dose levels from 25 mg every other day (QOD) - 200 mg daily (QD) on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. |
Drug: Derazantinib low dose range
Derazantinib was administered orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule.
|
| Experimental: Middle Dose Group Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. |
Drug: Derazantinib middle dose range
Derazantinib was administered orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule.
|
| Experimental: High Dose Group Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. |
Drug: Derazantinib high dose range
Derazantinib was administered orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule.
|
| Experimental: Expanded Cohort Group Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. |
Drug: Derazantinib at recommended phase 2 dose (RP2D)
Derazantinib was administered orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule.
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Drug-related Treatment-emergent Adverse Events (TEAEs) [Adverse events were collected and reported from the time of receiving first dose of derazantinib to the end of study assessment and follow-up period (30-day post-treatment)]
Adverse events were graded for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. CTCAE is classifying AEs and their associated severity from Grade 1 (Mild AE), Grade 2 (Moderate AE), Grade 3 (Severe or medically significant but not immediately life-threatening), Grade 4 (Life-threatening consequences) to Grade 5 (Death related to AE)
Secondary Outcome Measures
- Proportion of Patients With an Objective Tumor Response Per RECIST 1.1 [Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated.]
The number of patients with an objective tumor response, which included those with either a complete response (CR) or a partial response (PR) based on RECIST v1.1 guidelines which defines criteria for the radiological assessment in tumor response. The objective response rate (ORR) was defined as the proportion of patients with a CR or PR.
- Proportion of Patients With Disease Control Per RECIST 1.1 [Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated.]
The number of patients with tumor disease control, which included those with either a complete or partial tumor response, or a stable disease (SD) based on RECIST v1.1 guidelines which defines criteria for the radiological assessment in tumor response. The disease control rate (DCR) was defined as the proportion of patients with CR, PR or SD.
- Progression-free Survival (PFS) [Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated.]
PFS was calculated as the time from the date of first dose until documented radiographic disease progression or death from any cause, whichever occurred first. Disease progression is measured according to a specified radiologic increase in tumor size.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Signed written informed consent granted
-
Men or women ≥18 years of age
-
Histologically or cytologically confirmed, locally advanced, inoperable, or metastatic solid tumors. Patients eligible for enrollment in the Expanded Cohort must have documented and/or confirmed FGFR genetic aberrations, including iCCA with FGFR2 gene fusion.
-
Failure to respond to standard therapy, or for whom standard therapy does not exist.
-
Evaluable or measurable disease
-
Archival and/or fresh biopsy tissue samples must be available prior to the first dose of the study drug
-
Life expectancy ≥ 12 weeks
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
-
Hemoglobin (Hgb) ≥ 9.0 g/dL
-
Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
-
Platelet count ≥ 100 x 10^9/L
-
Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (≤ 2 x ULN for patients with cholangiocarcinoma)
-
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × ULN (≤ 5 x ULN for patients with liver metastases)
-
Serum creatinine ≤ 1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
-
Albumin ≥ 2.8 g/dL
-
INR 0.8 to ULN or ≤ 3 for patients receiving anticoagulant therapy
-
Men or women of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoid intercourse during the study and for 90 days after the last dose of study drug
-
Women of childbearing potential must have a negative serum pregnancy test during Screening Period and within 48 hours of the first dose of derazantinib.
Exclusion Criteria:
-
Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks or five times of the drug half life, whichever is longer, of the first dose of derazantinib
-
Major surgery or radiation therapy within four weeks of the first dose of derazantinib
-
Previous treatment with FGFR inhibitors
-
History of allergic reactions attributed to compounds of similar chemical or biological composition as derazantinib
-
Unable or unwilling to swallow the complete daily dose of derazantinib
-
Clinically unstable central nervous system (CNS) metastasis
-
History of myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association classification within 6 months of the first dose of derazantinib (MI occurring >6 months of the first dose of derazantinib will be permitted)
-
Significant GI disorder(s) that could interfere with the absorption, metabolism, or excretion of derazantinib (e.g. Crohn's disease, ulcerative colitis, extensive gastric resection)
-
History and/or current evidence of clinically relevant ectopic mineralization/calcification
-
Previous malignancy within 2 years prior to the first dose of derazantinib, except curatively treated non-melanoma skin cancer, carcinoma in-situ of the breast or cervix, or superficial bladder tumors
-
Known human immunodeficiency virus (HIV) infection
-
Concurrent uncontrolled illness not related to cancer, including but not limited to:
-
Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements.
-
Uncontrolled diabetes mellitus
-
Blood transfusion within 5 days of the blood draw being used to confirm eligibility
-
Pregnant or breastfeeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Scottsdale Healthcare Research Institute | Scottsdale | Arizona | United States | 85258 |
| 2 | Emory University, Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 3 | Karmanos Cancer Institute, Detroit | Detroit | Michigan | United States | 48201 |
| 4 | Comprehensive Cancer Centers of Nevada | Las Vegas | Nevada | United States | 89169 |
| 5 | Montefiore-Einstein Center for Cancer Care | Bronx | New York | United States | 10467 |
| 6 | University of Pennsylvania Hospital | Philadelphia | Pennsylvania | United States | 19104 |
| 7 | START - South Texas Accelerated Research Therapeutics, LLC | San Antonio | Texas | United States | 78229 |
| 8 | University of Washington | Seattle | Washington | United States | 98109 |
| 9 | Istituto Clinico Humanitas | Milan | Italy | 20089 | |
| 10 | Istituto Nazionale Tumori (National Cancer Institute) | Milan | Italy | 20133 | |
| 11 | Instituto Oncologico Veneto, IRCCS | Padova | Italy | 35128 | |
| 12 | Azienda Ospedaliero-Universitaria Pisana - U.O. Oncologia Medica 2 Univ. | Pisa | Italy | 56126 |
Sponsors and Collaborators
- Basilea Pharmaceutica
- ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Investigators
- Study Director: Marc Engelhardt, MD, Basilea Pharmaceutica
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Basilea Pharmaceutica
ClinicalTrials.gov Identifier:
NCT01752920
Other Study ID Numbers:
- ARQ 087-101
First Posted:
Dec 19, 2012
Last Update Posted:
Mar 9, 2022
Last Verified:
Mar 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Keywords provided by Basilea Pharmaceutica
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted in 12 study centers, 8 in the US and 4 in Italy. 119 subjects were recruited between December 2012 and January 2017. |
|---|---|
| Pre-assignment Detail | A fresh core needle biopsy or fine needle aspiration could be collected during the screening period if archival tumor tissue biopsy samples were not available. |
| Arm/Group Title | Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group | Derazantinib 250 mg QOD - 325 mg QD -Middle Dose Group | Derazantinib 400 mg QOD - 425 mg QD - High Dose Group | Derazantinib 300 mg QD - Expanded Cohort Group |
|---|---|---|---|---|
| Arm/Group Description | Subjects who received derazantinib orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Subjects who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Subjects who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Subjects who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. |
| Period Title: Overall Study | ||||
| STARTED | 29 | 13 | 19 | 58 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 29 | 13 | 19 | 58 |
Baseline Characteristics
| Arm/Group Title | Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group | Derazantinib 250 mg QOD - 325 mg QD - Middle Dose Group | Derazantinib 400 mg QOD - 425 mg QD - High Dose Group | Derazantinib 300 mg QD - Expanded Cohort Group | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Patients who received derazantinib orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Total of all reporting groups |
| Overall Participants | 29 | 13 | 19 | 58 | 119 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
19
65.5%
|
4
30.8%
|
8
42.1%
|
35
60.3%
|
66
55.5%
|
| >=65 years |
10
34.5%
|
9
69.2%
|
11
57.9%
|
23
39.7%
|
53
44.5%
|
| Age (years) [Median (Full Range) ] | |||||
| Median (Full Range) [years] |
60
|
67
|
66
|
60.5
|
63
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
17
58.6%
|
9
69.2%
|
11
57.9%
|
32
55.2%
|
69
58%
|
| Male |
12
41.4%
|
4
30.8%
|
8
42.1%
|
26
44.8%
|
50
42%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
3
10.3%
|
1
7.7%
|
3
15.8%
|
2
3.4%
|
9
7.6%
|
| Not Hispanic or Latino |
26
89.7%
|
12
92.3%
|
16
84.2%
|
56
96.6%
|
110
92.4%
|
| Unknown or Not Reported |
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%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
10.3%
|
1
7.7%
|
2
10.5%
|
3
5.2%
|
9
7.6%
|
| White |
24
82.8%
|
11
84.6%
|
16
84.2%
|
54
93.1%
|
105
88.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
2
6.9%
|
1
7.7%
|
1
5.3%
|
1
1.7%
|
5
4.2%
|
Outcome Measures
| Title | Number of Patients With Drug-related Treatment-emergent Adverse Events (TEAEs) |
|---|---|
| Description | Adverse events were graded for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. CTCAE is classifying AEs and their associated severity from Grade 1 (Mild AE), Grade 2 (Moderate AE), Grade 3 (Severe or medically significant but not immediately life-threatening), Grade 4 (Life-threatening consequences) to Grade 5 (Death related to AE) |
| Time Frame | Adverse events were collected and reported from the time of receiving first dose of derazantinib to the end of study assessment and follow-up period (30-day post-treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all subjects who received at least one dose of derazantinib. |
| Arm/Group Title | Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group | Derazantinib 250 mg QOD - 325 mg QD - Middle Dose Group | Derazantinib 400 mg QOD - 425 mg QD - High Dose Group | Derazantinib 300 mg QD - Expanded Cohort Group |
|---|---|---|---|---|
| Arm/Group Description | Patients who received derazantinib orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. |
| Measure Participants | 29 | 13 | 19 | 58 |
| TEAE Grade 1 |
3
10.3%
|
1
7.7%
|
1
5.3%
|
11
19%
|
| TEAE Grade 2 |
14
48.3%
|
5
38.5%
|
3
15.8%
|
14
24.1%
|
| TEAE Grade 3 |
9
31%
|
6
46.2%
|
13
68.4%
|
24
41.4%
|
| TEAE Grade 4 |
0
0%
|
1
7.7%
|
0
0%
|
4
6.9%
|
| TEAE Grade 5 |
2
6.9%
|
0
0%
|
2
10.5%
|
5
8.6%
|
| no TEAE |
1
3.4%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Proportion of Patients With an Objective Tumor Response Per RECIST 1.1 |
|---|---|
| Description | The number of patients with an objective tumor response, which included those with either a complete response (CR) or a partial response (PR) based on RECIST v1.1 guidelines which defines criteria for the radiological assessment in tumor response. The objective response rate (ORR) was defined as the proportion of patients with a CR or PR. |
| Time Frame | Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable Population: patients who received at least one cycle of study treatment and had at least one postbaseline tumor evaluation. |
| Arm/Group Title | Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group | Derazantinib 250 mg QOD - 325 mg QD -Middle Dose Group | Derazantinib 400 mg QOD - 425 mg QD - High Dose Group | Derazantinib 300 mg QD - Expanded Cohort Group |
|---|---|---|---|---|
| Arm/Group Description | Patients who received derazantinib orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. |
| Measure Participants | 29 | 13 | 19 | 58 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
1
5.3%
|
5
8.6%
|
| Title | Proportion of Patients With Disease Control Per RECIST 1.1 |
|---|---|
| Description | The number of patients with tumor disease control, which included those with either a complete or partial tumor response, or a stable disease (SD) based on RECIST v1.1 guidelines which defines criteria for the radiological assessment in tumor response. The disease control rate (DCR) was defined as the proportion of patients with CR, PR or SD. |
| Time Frame | Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group | Derazantinib 250 mg QOD - 325 mg QD - Middle Dose Group | Derazantinib 400 mg QOD - 425 mg QD - High Dose Group | Derazantinib 300 mg QD - Expanded Cohort Group |
|---|---|---|---|---|
| Arm/Group Description | Patients who received derazantinib orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria . |
| Measure Participants | 29 | 13 | 19 | 58 |
| Count of Participants [Participants] |
8
27.6%
|
4
30.8%
|
7
36.8%
|
32
55.2%
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | PFS was calculated as the time from the date of first dose until documented radiographic disease progression or death from any cause, whichever occurred first. Disease progression is measured according to a specified radiologic increase in tumor size. |
| Time Frame | Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group | Derazantinib 250 mg QOD - 325 mg QD -Middle Dose Group | Derazantinib 400 mg QOD - 425 mg QD - High Dose Group | Derazantinib 300 mg QD - Expanded Cohort Group |
|---|---|---|---|---|
| Arm/Group Description | Patients who received derazantinib orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. |
| Measure Participants | 29 | 13 | 19 | 58 |
| Median (95% Confidence Interval) [weeks] |
8.3
|
15.3
|
8.1
|
17.4
|
Adverse Events
| Time Frame | Adverse events were recorded from the first administration of study drug up to 30 days after the last study drug administration. The average period of time for AE data collection was 28 weeks. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | |||||||
| Arm/Group Title | Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group | Derazantinib 250 mg QOD - 325 mg QD -Middle Dose Group | Derazantinib 400 mg QOD - 425 mg QD - High Dose Group | Derazantinib 300 mg QD - Expanded Cohort Group | ||||
| Arm/Group Description | Patients who received derazantinib orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria. | ||||
All Cause Mortality |
||||||||
| Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group | Derazantinib 250 mg QOD - 325 mg QD -Middle Dose Group | Derazantinib 400 mg QOD - 425 mg QD - High Dose Group | Derazantinib 300 mg QD - Expanded Cohort Group | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/29 (6.9%) | 0/13 (0%) | 2/19 (10.5%) | 5/58 (8.6%) | ||||
Serious Adverse Events |
||||||||
| Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group | Derazantinib 250 mg QOD - 325 mg QD -Middle Dose Group | Derazantinib 400 mg QOD - 425 mg QD - High Dose Group | Derazantinib 300 mg QD - Expanded Cohort Group | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/29 (31%) | 2/13 (15.4%) | 6/19 (31.6%) | 16/58 (27.6%) | ||||
| Cardiac disorders | ||||||||
| Cardiomyopathy | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Enterocutaneous fistula | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Nausea | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 2 | 1/58 (1.7%) | 1 |
| Odynophagia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Rectal haemorrhage | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Small intestinal obstruction | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Stomatitis | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Upper gastrointestinal haemorrhage | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Vomiting | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 1/58 (1.7%) | 1 |
| General disorders | ||||||||
| Chest pain | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Disease progression | 2/29 (6.9%) | 2 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 3/58 (5.2%) | 3 |
| General physical health deterioration | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 3/58 (5.2%) | 3 |
| Pyrexia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 2/58 (3.4%) | 3 |
| Hepatobiliary disorders | ||||||||
| Cholangitis | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Cholangitis acute | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Infections and infestations | ||||||||
| Abdominal wall abscess | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Appendicitis | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Pneumonia | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 3/58 (5.2%) | 3 |
| Pyelonephritis | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Sepsis | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Urinary tract infection | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Investigations | ||||||||
| Electrocardiogram QT prolonged | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Electrocardiogram abnormal | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 2/58 (3.4%) | 2 |
| Hypokalaemia | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Breast cancer metastatic | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Malignant pleural effusion | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Nervous system disorders | ||||||||
| Dizziness | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Encephalopathy | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Spinal cord injury cervical | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Syncope | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Female genital tract fistula | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Hypoxia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 2/19 (10.5%) | 2 | 0/58 (0%) | 0 |
| Pneumothorax | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Vascular disorders | ||||||||
| Hypertension | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||
| Derazantinib 25 mg QOD - 200 mg QD - Low Dose Group | Derazantinib 250 mg QOD - 325 mg QD -Middle Dose Group | Derazantinib 400 mg QOD - 425 mg QD - High Dose Group | Derazantinib 300 mg QD - Expanded Cohort Group | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 28/29 (96.6%) | 13/13 (100%) | 19/19 (100%) | 58/58 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 7/29 (24.1%) | 12 | 3/13 (23.1%) | 4 | 0/19 (0%) | 0 | 10/58 (17.2%) | 18 |
| Leukopenia | 1/29 (3.4%) | 2 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 2/58 (3.4%) | 2 |
| Lymphopenia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 1/58 (1.7%) | 1 |
| Thrombocytopenia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 3/19 (15.8%) | 3 | 3/58 (5.2%) | 4 |
| Cardiac disorders | ||||||||
| Cardiomegaly | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Pericardial effusion | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Tachycardia | 2/29 (6.9%) | 2 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||||
| Ichthyosis | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||
| Ear pain | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Hearing impaired | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Tinnitus | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Endocrine disorders | ||||||||
| Hypothyroidism | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Eye disorders | ||||||||
| Conjunctivitis | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 5/58 (8.6%) | 9 |
| Dry eye | 1/29 (3.4%) | 2 | 2/13 (15.4%) | 2 | 0/19 (0%) | 0 | 7/58 (12.1%) | 8 |
| Lacrimation increased | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Vision blurred | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 7/58 (12.1%) | 14 |
| Visual acuity reduced | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 5/58 (8.6%) | 5 |
| Visual impairment | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 3/29 (10.3%) | 4 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 1 | 6/58 (10.3%) | 6 |
| Abdominal pain | 2/29 (6.9%) | 2 | 2/13 (15.4%) | 2 | 1/19 (5.3%) | 2 | 5/58 (8.6%) | 5 |
| Abdominal pain upper | 1/29 (3.4%) | 1 | 3/13 (23.1%) | 5 | 0/19 (0%) | 0 | 2/58 (3.4%) | 2 |
| Ascites | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 4/58 (6.9%) | 5 |
| Cheilitis | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 1/58 (1.7%) | 1 |
| Constipation | 5/29 (17.2%) | 5 | 4/13 (30.8%) | 5 | 7/19 (36.8%) | 9 | 16/58 (27.6%) | 20 |
| Diarrhoea | 6/29 (20.7%) | 11 | 5/13 (38.5%) | 5 | 9/19 (47.4%) | 10 | 17/58 (29.3%) | 37 |
| Dry mouth | 3/29 (10.3%) | 3 | 1/13 (7.7%) | 1 | 6/19 (31.6%) | 8 | 19/58 (32.8%) | 23 |
| Dyspepsia | 3/29 (10.3%) | 3 | 0/13 (0%) | 0 | 3/19 (15.8%) | 3 | 6/58 (10.3%) | 7 |
| Flatulence | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 3/58 (5.2%) | 3 |
| Frequent bowel movements | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/29 (0%) | 0 | 2/13 (15.4%) | 2 | 3/19 (15.8%) | 4 | 1/58 (1.7%) | 1 |
| Hiatus hernia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Intestinal obstruction | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Lip disorder | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Lip dry | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Lip pain | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Nausea | 14/29 (48.3%) | 18 | 8/13 (61.5%) | 14 | 13/19 (68.4%) | 15 | 27/58 (46.6%) | 46 |
| Odynophagia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Oesophagitis | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Oral dysaesthesia | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Stomatitis | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 4/58 (6.9%) | 6 |
| Tongue disorder | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Vomiting | 10/29 (34.5%) | 11 | 2/13 (15.4%) | 5 | 7/19 (36.8%) | 7 | 23/58 (39.7%) | 48 |
| General disorders | ||||||||
| Asthenia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 13/58 (22.4%) | 26 |
| Chest pain | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 4/58 (6.9%) | 4 |
| Discomfort | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Fatigue | 18/29 (62.1%) | 24 | 8/13 (61.5%) | 14 | 11/19 (57.9%) | 18 | 26/58 (44.8%) | 40 |
| Feeling abnormal | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Feeling hot | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Gait disturbance | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 2/19 (10.5%) | 2 | 2/58 (3.4%) | 2 |
| Malaise | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 2 | 1/58 (1.7%) | 1 |
| Mucosal inflammation | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 3/58 (5.2%) | 3 |
| Non-cardiac chest pain | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Oedema | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Oedema peripheral | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 1 | 4/58 (6.9%) | 5 |
| Pain | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 1/58 (1.7%) | 2 |
| Performance status decreased | 2/29 (6.9%) | 2 | 1/13 (7.7%) | 2 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Pyrexia | 3/29 (10.3%) | 4 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 6/58 (10.3%) | 9 |
| Infections and infestations | ||||||||
| Candidiasis | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 1 | 1/58 (1.7%) | 1 |
| Cystitis | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 1 | 2/58 (3.4%) | 3 |
| Ear infection | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Oesophageal candidiasis | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Oral herpes | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Pharyngitis | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Pneumonia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Skin infection | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Upper respiratory tract infection | 2/29 (6.9%) | 2 | 0/13 (0%) | 0 | 2/19 (10.5%) | 2 | 2/58 (3.4%) | 2 |
| Urinary tract infection | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 2/19 (10.5%) | 2 | 2/58 (3.4%) | 3 |
| Injury, poisoning and procedural complications | ||||||||
| Arthropod bite | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Contusion | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 1 | 2/58 (3.4%) | 2 |
| Excoriation | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Fall | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 3/19 (15.8%) | 4 | 1/58 (1.7%) | 1 |
| Head injury | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Joint injury | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Rib fracture | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Scratch | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 2/29 (6.9%) | 2 | 3/13 (23.1%) | 3 | 4/19 (21.1%) | 6 | 17/58 (29.3%) | 31 |
| Aspartate aminotransferase increased | 7/29 (24.1%) | 10 | 7/13 (53.8%) | 10 | 10/19 (52.6%) | 14 | 17/58 (29.3%) | 30 |
| Bilirubin conjugated increased | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Blood alkaline phosphatase increased | 8/29 (27.6%) | 8 | 2/13 (15.4%) | 2 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Blood creatine phosphokinase increased | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Blood creatinine increased | 4/29 (13.8%) | 4 | 1/13 (7.7%) | 1 | 4/19 (21.1%) | 4 | 4/58 (6.9%) | 5 |
| Blood lactate dehydrogenase increased | 5/29 (17.2%) | 6 | 2/13 (15.4%) | 2 | 3/19 (15.8%) | 3 | 0/58 (0%) | 0 |
| Blood thyroid stimulating hormone increased | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Blood urea increased | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 3/19 (15.8%) | 3 | 0/58 (0%) | 0 |
| Breath sounds abnormal | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 2/19 (10.5%) | 2 | 0/58 (0%) | 0 |
| Electrocardiogram QT interval abnormal | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 1/58 (1.7%) | 1 |
| Electrocardiogram QT prolonged | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Visual acuity tests abnormal | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Weight decreased | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 2/19 (10.5%) | 2 | 2/58 (3.4%) | 2 |
| Metabolism and nutrition disorders | ||||||||
| Cachexia | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Decreased appetite | 12/29 (41.4%) | 14 | 3/13 (23.1%) | 6 | 6/19 (31.6%) | 8 | 13/58 (22.4%) | 15 |
| Dehydration | 2/29 (6.9%) | 2 | 0/13 (0%) | 0 | 4/19 (21.1%) | 5 | 3/58 (5.2%) | 4 |
| Hypercalcaemia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 3/19 (15.8%) | 3 | 0/58 (0%) | 0 |
| Hyperglycaemia | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 2/58 (3.4%) | 2 |
| Hyperkalaemia | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 3/58 (5.2%) | 6 |
| Hyperphosphataemia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 2/58 (3.4%) | 2 |
| Hypoalbuminaemia | 6/29 (20.7%) | 10 | 3/13 (23.1%) | 4 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Hypochloraemia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Hypokalaemia | 3/29 (10.3%) | 3 | 3/13 (23.1%) | 4 | 2/19 (10.5%) | 3 | 1/58 (1.7%) | 1 |
| Hypomagnesaemia | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 1 | 1/58 (1.7%) | 1 |
| Hyponatraemia | 2/29 (6.9%) | 2 | 0/13 (0%) | 0 | 3/19 (15.8%) | 4 | 5/58 (8.6%) | 6 |
| Hypophosphataemia | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Vitamin D deficiency | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 2/29 (6.9%) | 2 | 1/13 (7.7%) | 1 | 2/19 (10.5%) | 3 | 4/58 (6.9%) | 4 |
| Muscle twitching | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Muscular weakness | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Musculoskeletal pain | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 2/58 (3.4%) | 2 |
| Pain in extremity | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 1/58 (1.7%) | 3 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Tumour pain | 3/29 (10.3%) | 3 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 2/58 (3.4%) | 2 |
| Nervous system disorders | ||||||||
| Ataxia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Balance disorder | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 1/58 (1.7%) | 1 |
| Burning sensation | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 2 | 0/58 (0%) | 0 |
| Clumsiness | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Dizziness | 2/29 (6.9%) | 2 | 1/13 (7.7%) | 1 | 5/19 (26.3%) | 11 | 9/58 (15.5%) | 15 |
| Dizziness postural | 0/29 (0%) | 0 | 2/13 (15.4%) | 2 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Dysgeusia | 3/29 (10.3%) | 3 | 3/13 (23.1%) | 3 | 3/19 (15.8%) | 3 | 11/58 (19%) | 14 |
| Head discomfort | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Headache | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 3/19 (15.8%) | 5 | 12/58 (20.7%) | 14 |
| Hypoaesthesia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Memory impairment | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 2/19 (10.5%) | 2 | 0/58 (0%) | 0 |
| Neuropathy peripheral | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 4/58 (6.9%) | 7 |
| Paraesthesia | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 2/58 (3.4%) | 2 |
| Peripheral motor neuropathy | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Somnolence | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 5/58 (8.6%) | 5 |
| Tremor | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 4/58 (6.9%) | 6 |
| Psychiatric disorders | ||||||||
| Anxiety | 4/29 (13.8%) | 5 | 3/13 (23.1%) | 3 | 2/19 (10.5%) | 3 | 2/58 (3.4%) | 2 |
| Depression | 3/29 (10.3%) | 4 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 3/58 (5.2%) | 3 |
| Hallucination | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Insomnia | 2/29 (6.9%) | 2 | 1/13 (7.7%) | 1 | 2/19 (10.5%) | 2 | 4/58 (6.9%) | 4 |
| Renal and urinary disorders | ||||||||
| Dysuria | 2/29 (6.9%) | 2 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 1/58 (1.7%) | 2 |
| Hydronephrosis | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Micturition frequency decreased | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Pollakiuria | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Proteinuria | 3/29 (10.3%) | 5 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Urinary incontinence | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Vaginal haemorrhage | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 4/29 (13.8%) | 4 | 0/13 (0%) | 0 | 1/19 (5.3%) | 2 | 7/58 (12.1%) | 7 |
| Dysphonia | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Dyspnoea | 6/29 (20.7%) | 6 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 5/58 (8.6%) | 5 |
| Epistaxis | 0/29 (0%) | 0 | 1/13 (7.7%) | 2 | 0/19 (0%) | 0 | 8/58 (13.8%) | 9 |
| Hypoxia | 1/29 (3.4%) | 1 | 0/13 (0%) | 0 | 1/19 (5.3%) | 4 | 0/58 (0%) | 0 |
| Laryngeal inflammation | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Nasal congestion | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 4/58 (6.9%) | 4 |
| Nasal dryness | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Nasal mucosal disorder | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Oropharyngeal pain | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 1 | 3/58 (5.2%) | 3 |
| Productive cough | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 1/58 (1.7%) | 1 |
| Pulmonary congestion | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Respiratory failure | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Rhinorrhoea | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Throat irritation | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Wheezing | 1/29 (3.4%) | 2 | 0/13 (0%) | 0 | 2/19 (10.5%) | 2 | 0/58 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Alopecia | 1/29 (3.4%) | 2 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 1 | 11/58 (19%) | 11 |
| Decubitus ulcer | 2/29 (6.9%) | 2 | 0/13 (0%) | 0 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Dry skin | 2/29 (6.9%) | 2 | 2/13 (15.4%) | 2 | 5/19 (26.3%) | 6 | 5/58 (8.6%) | 5 |
| Erythema | 2/29 (6.9%) | 2 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 2/58 (3.4%) | 2 |
| Nail discolouration | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Night sweats | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Onychomadesis | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Photosensitivity reaction | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Pruritus | 2/29 (6.9%) | 2 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 3/58 (5.2%) | 3 |
| Rash | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 4/58 (6.9%) | 4 |
| Rash erythematous | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Rash macular | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Rash maculo-papular | 3/29 (10.3%) | 3 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 1/58 (1.7%) | 1 |
| Scab | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Scar | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Skin fissures | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Skin mass | 0/29 (0%) | 0 | 1/13 (7.7%) | 1 | 2/19 (10.5%) | 3 | 0/58 (0%) | 0 |
| Vascular disorders | ||||||||
| Flushing | 1/29 (3.4%) | 1 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
| Haematoma | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 1/19 (5.3%) | 1 | 0/58 (0%) | 0 |
| Hypertension | 0/29 (0%) | 0 | 0/13 (0%) | 0 | 4/19 (21.1%) | 4 | 5/58 (8.6%) | 5 |
| Hypotension | 2/29 (6.9%) | 2 | 1/13 (7.7%) | 1 | 0/19 (0%) | 0 | 0/58 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Basilea Pharmaceutica International Ltd. |
| Phone | +41615671546 |
| marc.engelhardt@basilea.com |
Responsible Party:
Basilea Pharmaceutica
ClinicalTrials.gov Identifier:
NCT01752920
Other Study ID Numbers:
- ARQ 087-101
First Posted:
Dec 19, 2012
Last Update Posted:
Mar 9, 2022
Last Verified:
Mar 1, 2022