Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer
Study Details
Study Description
Brief Summary
This phase II trial studies the side effects and how well pazopanib hydrochloride works in treating patients with advanced thyroid cancer. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by stopping blood flow to the tumor.
Detailed Description
PRIMARY OBJECTIVE:
- To establish the safety and efficacy of GW786034 (pazopanib hydrochloride) as a therapeutic in patients afflicted with differentiated, medullary and anaplastic thyroid cancers.
CORRELATIVE OBJECTIVES:
-
Assessment of the impact of therapy with GW786034 on serum/plasma vascular endothelial growth factor (VEGF) levels.
-
To explore the potential relationship between changes in thyroglobulin levels and tumor response in patients with advanced differentiated thyroid cancer known to be thyroglobulin antibody negative.
OUTLINE:
Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 3 years after registration.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 (DTC) Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Pazopanib Hydrochloride
Given PO
Other Names:
|
| Experimental: Cohort 2 (MTC) Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Drug: Pazopanib Hydrochloride
Given PO
Other Names:
|
| Experimental: Cohort 3 (ATC) Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Other: Laboratory Biomarker Analysis
Correlative studies
|
| Experimental: Expansion Cohort (DTC) Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Pazopanib Hydrochloride
Given PO
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (in Cohorts 1-3) [Up to 3 years]
The tumor response rate is defined as the percentage of eligible patients who fulfill RECIST 1.0 for a complete or partial response at two consecutive assessments at least 8 weeks apart for patients in Cohorts 1-3. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Confirmed Tumor Response (in the Differentiated Thyroid Cancer Expansion Cohort) [Up to 3 years]
The confirmed tumor response rate is defined as the percentage of eligible patients who fulfill RECIST 1.0 for a complete or partial response at two consecutive assessments at least 8 weeks apart for patients with differentiated thyroid cancer who are thyroglobulin antibody negative. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcome Measures
- Toxicity as Measured by the Percentage of Patients Reporting a Grade 3+ Adverse Event Deemed Possibly, Probably, or Definitely Related to Treatment [Up to 3 years]
Toxicity (defined as grade 3+ adverse events deemed possibly, probably, or definitely related to treatment) will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The percentage of patients with grade 3+ adverse events deemed possibly, probably, or definitely related to treatment are reported for patients in Cohorts 1-3.
- Progression-Free Survival at 6 Months (Cohorts 1 and 2 Only) [Time from registration to the date of progression or last follow-up, whichever comes first, assessed up to 6 months]
Progression free survival at 6 months (PFS6) is defined as the proportion of patients alive and without progression at 6 months. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.
- Progression-Free Survival at 3 Months (Cohort 3 Only) [Time from registration to the date of progression or last follow-up, whichever comes first, assessed up to 3 months]
Progression free survival at 3 months (PFS6) is defined as the proportion of patients alive and without progression at 3 months. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.
Other Outcome Measures
- Change in Blood Markers for Angiogenesis [Baseline to up to 3 years]
Blood markers for angiogenesis including levels of free VEGF, free GW786034, and GW786034/VEGF complexes will be evaluated before and during therapy. Changes in these levels will largely be explored in a graphical manner as well as exploring any potential relationships between these levels and clinical outcome such as response or progression-free rate and toxicity incidence.
- Proportion of Patients With Differentiated Thyroid Cancer and Medullary Thyroid Cancer Who Have Not Failed Treatment at 6 Months (3 Months for Anaplastic Thyroid Cancer) [Up to 6 months]
The proportion of patients who have not failed treatment due to disease progression, adverse reactions, refusal for further participation, or who went on to alternate therapy at 6 months (3 months for anaplastic thyroid cancer patients) will be calculated and summarized independently within each of the patient groups. Assuming that the incidence of response is binomially distributed, 90% binomial confidence intervals will also be calculated.
- Overall Survival [Time from registration to date of last follow-up or death due to any cause, assessed up to 3 years]
Overall survival time is defined as the time from registration to death due to any cause. The median is estimated using the Kaplan-Meier estimator.> Estimated using the method of Kaplan-Meier.
- Time to Treatment Failure [Time from registration to the date the patient discontinues treatment, assessed up to 3 years]
Estimated using the method of Kaplan-Meier.
- Time to Subsequent Therapy [Up to 3 years]
Estimated using the method of Kaplan-Meier.
- Duration of Response [Time from registration to the date the patient discontinues treatment, assessed up to 3 years]
Duration of response is defined for all evaluable patients who have achieved a confirmed response as the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression (PD) is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by >= 50% of previously involved sites from nadir). Duration of response will be assessed.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically or cytologically confirmed differentiated, medullary or anaplastic thyroid cancer that is now advanced or metastatic; NOTE: patients with thyroid lymphomas or sarcomas are specifically excluded, as are patients with metastatic disease from other sites of origin to thyroid
-
Patients with confirmed differentiated thyroid cancer to be enrolled in the expanded/additional differentiated thyroid cancer (DTC) cohort must be thyroglobulin antibody negative
-
Zero, one or two prior therapeutic regimens (this includes cytotoxic plus non-cytotoxic therapeutic regimens)
-
Absence of sensitivity to therapeutic radioiodine (differentiated only)
-
Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan; NOTE: disease that is measurable by physical examination only is not eligible
-
Life expectancy > 3 months
-
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 (Karnofsky >= 60%)
-
Leukocytes > 3,000/mcL obtained =< 7 days prior to registration
-
Absolute neutrophil count > 1,500/mcL obtained =< 7 days prior to registration
-
Platelets > 100,000/mcL obtained =< 7 days prior to registration
-
Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) obtained =< 7 days prior to registration (if there is reason to believe that the patient has Gilbert's syndrome, the bilirubin can be fractionated; if the fractionated bilirubin is consistent with Gilbert's syndrome and there is no other possible explanation for the elevated indirect bilirubin, the patient may be eligible for the study if and only if the direct bilirubin is =< 1.5 X institutional ULN)
-
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 2.5 X institutional ULN obtained =< 7 days prior to registration
-
Creatinine =< 1.5 X ULN obtained =< 7 days prior to registration
-
Proteinuria =< + on urinalysis (may re-check) obtained =< 7 days prior to registration
-
International normalized ratio (INR) =< 1.2 X the ULN obtained =< 7 days prior to registration
-
Blood pressure (BP) < 140 mmHg (systolic) and < 90 mmHg (diastolic); initiation or adjustment of BP medication is permitted prior to registration provided that the average of three BP readings at a visit prior to registration is < 140/90 mmHg
-
Objective evidence of tumor progression in the 6 month period prior to GW786034 initiation as assessed by:
-
Unequivocal progression of objectively measured disease on successive appropriate imaging (e.g. CT scan); in cases of uncertainty of tumor progression, the principal investigator of the study will be available to assist in decisions
-
Women of child-bearing potential must have a negative serum pregnancy test =< 7 days prior to registration; NOTE: women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; effective contraception is required for all fertile participants in the trial
-
Ability to understand and the willingness to sign a written informed consent document
-
Willingness to comply with the requirement of the study
-
Willingness to donate blood for correlative marker studies; (only applicable to sites within the United States)
Exclusion Criteria:
- Anaplastic, differentiated, medullary: a total of > 2 prior therapeutic regimens (this total includes cytotoxic plus non-cytotoxic regimens); Note: enrollment of anaplastic, differentiated, and medullary patients who have had zero, one or two prior therapeutic regimens (cytotoxic plus non-cytotoxic regimens) is allowed - provided therapy ceased
21 days prior to registration;
-
NOTE: the principal investigator of the study should be contacted in the event of uncertainty related patient eligibility based upon prior therapies
-
Disease that is measurable by physical examination only
-
Any of the following:
-
Radiotherapy =< 4 weeks prior to registration
-
Major surgery =< 4 weeks prior to registration
-
Radiotherapy to >= 25% of bone marrow
-
Concurrent therapy with octreotide unless tumor progression on this therapy has been demonstrated
-
Any other ongoing investigational agents
-
History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW786034 (pazopanib) or other agents used in the study
-
+1 proteinuria (< 30 mg/dL) on two consecutive dipstick or other urine assessments taken at least 1 week apart; NOTE: (in cases where questions arise related to disparate proteinuria measurements, the study principal investigator [PI] should be consulted for assistance in determining patient study eligibility)
-
Corrected QT interval (QTc) prolongation (defined as a QTc interval >= 480 msecs) or other significant electrocardiogram (ECG) abnormalities (e.g. frequent ventricular ectopy, evidence of ongoing myocardial ischemia); NOTE: the principal investigator of the study should be contacted in the event of uncertainty related patient eligibility based upon ECG changes
-
Receiving cytochrome P450 (CYP) interactive concomitant medications; certain medications that act through the CYP450 system are specifically prohibited in patients receiving GW786034 (pazopanib) because in vitro data indicate that the agent has the potential to interact with the cytochrome P450 isoenzymes cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) and cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); certain other agents should be used with caution
-
Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain GSK786034 (pazopanib)
-
Any of the following conditions:
-
Serious or non-healing wound, ulcer, or bone fracture
-
History of abdominal fistula, gastrointestinal perforation, active diverticulitis, intra-abdominal abscess or gastrointestinal tract bleeding =< 28 days of registration
-
Any history of cerebrovascular accident (CVA) =< 6 months
-
Current use of therapeutic warfarin; Note: low molecular weight heparin and prophylactic low-dose warfarin (INR < 1.2 X ULN) are permitted; prothrombin time (PT)/partial thromboplastin time (PTT) must meet the inclusion criteria
-
History of myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty or stenting within the last 12 weeks
-
History of venous thrombosis in last 12 weeks
-
Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; NOTE: a patient who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible
-
History of bleeding disorder, including patients afflicted with hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding
-
Poorly controlled depression or anxiety disorder, or recent (=< 6 months) suicidal ideation
-
Known active and/or untreated brain metastases and/or brain metastases requiring ongoing therapy (e.g. corticosteroids); NOTE: (because of the poor prognosis often associated with brain metastases and because of the potential risk of bleeding in active brain metastases associated with multi-targeted tyrosine kinase inhibitor therapy, patients with active and/or untreated brain metastases and/or those with brain metastases requiring ongoing therapy - e.g. corticosteroids - are excluded from trial enrollment; enrollment will, however, be permitted in cases of patients with longstanding treated and inactive brain metastases not requiring ongoing therapy, providing that stability of brain metastases has been demonstrated for a period of 3 months or greater as assessed by intracranial imaging - and providing that there is no indication of increased vascularity of the treated metastases by magnetic resonance imaging (MRI) imaging conducted =< 14 days prior to registration; when questions arise related to these criteria, the PI of the trial, Dr. Keith Bible, should be contacted for assistance on eligibility)
-
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would or might reasonably be expected to limit compliance with study requirements
-
Pregnant women; NOTE: (breastfeeding should be discontinued if the mother is treated with GW786034/pazopanib)
-
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy; NOTE: (appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated)
-
Receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of GW786034 (pazopanib); NOTE: the eligibility of patients will be determined following review of their case by the principal investigator; efforts should be made to switch patients who are taking enzyme-inducing anticonvulsant agents to other medications
-
Receiving any concomitant medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes; NOTE: these medications should be discontinued or replaced with drugs that do not carry these risks, if possible
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic in Arizona | Scottsdale | Arizona | United States | 85259 |
| 2 | University of Colorado Hospital | Aurora | Colorado | United States | 80045 |
| 3 | Mayo Clinic in Florida | Jacksonville | Florida | United States | 32224-9980 |
| 4 | University of Iowa/Holden Comprehensive Cancer Center | Iowa City | Iowa | United States | 52242 |
| 5 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
| 6 | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 7 | Fairview Ridges Hospital | Burnsville | Minnesota | United States | 55337 |
| 8 | Fairview-Southdale Hospital | Edina | Minnesota | United States | 55435 |
| 9 | Unity Hospital | Fridley | Minnesota | United States | 55432 |
| 10 | Minnesota Oncology Hematology PA-Maplewood | Maplewood | Minnesota | United States | 55109 |
| 11 | Abbott-Northwestern Hospital | Minneapolis | Minnesota | United States | 55407 |
| 12 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 13 | Park Nicollet Clinic - Saint Louis Park | Saint Louis Park | Minnesota | United States | 55416 |
| 14 | United Hospital | Saint Paul | Minnesota | United States | 55102 |
| 15 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 16 | University of Wisconsin Hospital and Clinics | Madison | Wisconsin | United States | 53792 |
| 17 | Sir Charles Gairdner Hospital | Nedlands | Western Australia | Australia | 6009 |
| 18 | Chinese University of Hong Kong-Prince of Wales Hospital | Shatin | Hong Kong | China | |
| 19 | National University Hospital Singapore | Singapore | Singapore | 119074 | |
| 20 | National Cancer Centre | Singapore | Singapore | 169610 | |
| 21 | Johns Hopkins Singapore | Singapore | Singapore | 308433 | |
| 22 | National Taiwan University Hospital | Taipei | Taiwan | 100 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Keith C Bible, Mayo Clinic
Study Documents (Full-Text)
More Information
Publications
None provided.- NCI-2009-00198
- NCI-2009-00198
- MC057H
- CDR0000588044
- 7627
- 7627
- N01CM00099
- N01CM62205
- P30CA015083
- NCT01648387
- NCT02653053
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) |
|---|---|---|---|---|
| Arm/Group Description | Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Period Title: Overall Study | ||||
| STARTED | 39 | 35 | 16 | 62 |
| COMPLETED | 37 | 35 | 15 | 60 |
| NOT COMPLETED | 2 | 0 | 1 | 2 |
Baseline Characteristics
| Arm/Group Title | Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Total of all reporting groups |
| Overall Participants | 37 | 35 | 15 | 60 | 147 |
| Age (years) [Median (Full Range) ] | |||||
| Median (Full Range) [years] |
63
|
60
|
66
|
60
|
61
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
18
48.6%
|
7
20%
|
10
66.7%
|
27
45%
|
62
42.2%
|
| Male |
19
51.4%
|
28
80%
|
5
33.3%
|
33
55%
|
85
57.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
1
2.7%
|
1
2.9%
|
1
6.7%
|
3
5%
|
6
4.1%
|
| Not Hispanic or Latino |
29
78.4%
|
33
94.3%
|
12
80%
|
57
95%
|
131
89.1%
|
| Unknown or Not Reported |
7
18.9%
|
1
2.9%
|
2
13.3%
|
0
0%
|
10
6.8%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
2
5.4%
|
7
20%
|
2
13.3%
|
17
28.3%
|
28
19%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
4
6.7%
|
4
2.7%
|
| White |
35
94.6%
|
28
80%
|
12
80%
|
37
61.7%
|
112
76.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
6.7%
|
2
3.3%
|
3
2%
|
| Region of Enrollment (participants) [Number] | |||||
| Singapore |
1
2.7%
|
3
8.6%
|
2
13.3%
|
3
5%
|
9
6.1%
|
| United States |
35
94.6%
|
26
74.3%
|
13
86.7%
|
38
63.3%
|
112
76.2%
|
| China |
0
0%
|
1
2.9%
|
0
0%
|
0
0%
|
1
0.7%
|
| Taiwan |
0
0%
|
3
8.6%
|
0
0%
|
10
16.7%
|
13
8.8%
|
| Australia |
1
2.7%
|
2
5.7%
|
0
0%
|
9
15%
|
12
8.2%
|
Outcome Measures
| Title | Overall Response Rate (in Cohorts 1-3) |
|---|---|
| Description | The tumor response rate is defined as the percentage of eligible patients who fulfill RECIST 1.0 for a complete or partial response at two consecutive assessments at least 8 weeks apart for patients in Cohorts 1-3. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Time Frame | Up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients in Cohort 1, Cohort 2, and Cohort 3 that received treatment and were eligible for response assessment were included in this analysis. |
| Arm/Group Title | Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) |
|---|---|---|---|---|
| Arm/Group Description | Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.> > Laboratory Biomarker Analysis: Correlative studies> > Pazopanib Hydrochloride: Given PO | Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.> > Pazopanib Hydrochloride: Given PO | Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.> > Laboratory Biomarker Analysis: Correlative studies | Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.> > Laboratory Biomarker Analysis: Correlative studies> > Pazopanib Hydrochloride: Given PO |
| Measure Participants | 37 | 35 | 15 | 0 |
| Number (95% Confidence Interval) [percentage of participants] |
49
132.4%
|
14
40%
|
0
0%
|
| Title | Confirmed Tumor Response (in the Differentiated Thyroid Cancer Expansion Cohort) |
|---|---|
| Description | The confirmed tumor response rate is defined as the percentage of eligible patients who fulfill RECIST 1.0 for a complete or partial response at two consecutive assessments at least 8 weeks apart for patients with differentiated thyroid cancer who are thyroglobulin antibody negative. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Time Frame | Up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that registered to the Differential Thyroid Expansion cohort and were evaluable for response assessment were included in this analysis. |
| Arm/Group Title | Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) |
|---|---|---|---|---|
| Arm/Group Description | Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Measure Participants | 0 | 0 | 0 | 60 |
| Number (95% Confidence Interval) [percentage of participants] |
37
100%
|
| Title | Toxicity as Measured by the Percentage of Patients Reporting a Grade 3+ Adverse Event Deemed Possibly, Probably, or Definitely Related to Treatment |
|---|---|
| Description | Toxicity (defined as grade 3+ adverse events deemed possibly, probably, or definitely related to treatment) will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The percentage of patients with grade 3+ adverse events deemed possibly, probably, or definitely related to treatment are reported for patients in Cohorts 1-3. |
| Time Frame | Up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that received protocol treatment and were assessed for adverse events are included in this analysis. |
| Arm/Group Title | Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) |
|---|---|---|---|---|
| Arm/Group Description | Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Measure Participants | 38 | 35 | 15 | 61 |
| Number [percentage of participants] |
40
108.1%
|
46
131.4%
|
53
353.3%
|
53
88.3%
|
| Title | Progression-Free Survival at 6 Months (Cohorts 1 and 2 Only) |
|---|---|
| Description | Progression free survival at 6 months (PFS6) is defined as the proportion of patients alive and without progression at 6 months. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. |
| Time Frame | Time from registration to the date of progression or last follow-up, whichever comes first, assessed up to 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients in Cohort 1 and Cohort 2 that received treatment and were eligible for response assessment were included in this analysis. |
| Arm/Group Title | Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) |
|---|---|---|---|---|
| Arm/Group Description | Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Measure Participants | 37 | 35 | 0 | 0 |
| Number (95% Confidence Interval) [proportion of participants] |
.71
1.9%
|
.686
2%
|
| Title | Progression-Free Survival at 3 Months (Cohort 3 Only) |
|---|---|
| Description | Progression free survival at 3 months (PFS6) is defined as the proportion of patients alive and without progression at 3 months. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. |
| Time Frame | Time from registration to the date of progression or last follow-up, whichever comes first, assessed up to 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients from Cohort 3 that were treated and evaluable for response were included in this analysis. |
| Arm/Group Title | Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) |
|---|---|---|---|---|
| Arm/Group Description | Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Measure Participants | 0 | 0 | 15 | 0 |
| Number (95% Confidence Interval) [proportion of participants] |
.267
0.7%
|
| Title | Change in Blood Markers for Angiogenesis |
|---|---|
| Description | Blood markers for angiogenesis including levels of free VEGF, free GW786034, and GW786034/VEGF complexes will be evaluated before and during therapy. Changes in these levels will largely be explored in a graphical manner as well as exploring any potential relationships between these levels and clinical outcome such as response or progression-free rate and toxicity incidence. |
| Time Frame | Baseline to up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Proportion of Patients With Differentiated Thyroid Cancer and Medullary Thyroid Cancer Who Have Not Failed Treatment at 6 Months (3 Months for Anaplastic Thyroid Cancer) |
|---|---|
| Description | The proportion of patients who have not failed treatment due to disease progression, adverse reactions, refusal for further participation, or who went on to alternate therapy at 6 months (3 months for anaplastic thyroid cancer patients) will be calculated and summarized independently within each of the patient groups. Assuming that the incidence of response is binomially distributed, 90% binomial confidence intervals will also be calculated. |
| Time Frame | Up to 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Overall Survival |
|---|---|
| Description | Overall survival time is defined as the time from registration to death due to any cause. The median is estimated using the Kaplan-Meier estimator.> Estimated using the method of Kaplan-Meier. |
| Time Frame | Time from registration to date of last follow-up or death due to any cause, assessed up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Treatment Failure |
|---|---|
| Description | Estimated using the method of Kaplan-Meier. |
| Time Frame | Time from registration to the date the patient discontinues treatment, assessed up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Subsequent Therapy |
|---|---|
| Description | Estimated using the method of Kaplan-Meier. |
| Time Frame | Up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Duration of Response |
|---|---|
| Description | Duration of response is defined for all evaluable patients who have achieved a confirmed response as the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression (PD) is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by >= 50% of previously involved sites from nadir). Duration of response will be assessed. |
| Time Frame | Time from registration to the date the patient discontinues treatment, assessed up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | Adverse events were collected at the end of every 28 day cycle, up to 84 cycles. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events were collected at the end of every 28 day cycle, up to 84 cycles. | |||||||
| Arm/Group Title | Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) | ||||
| Arm/Group Description | Patients with differentiated thyroid cancer (DTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with medullary thyroid cancer (MTC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with anaplastic thyroid cancer (ATC) receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Patients with confirmed, differentiated thyroid cancer (DTC) who are thyroglobulin antibody negative receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | ||||
All Cause Mortality |
||||||||
| Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/38 (7.9%) | 0/35 (0%) | 1/15 (6.7%) | 4/61 (6.6%) | ||||
Serious Adverse Events |
||||||||
| Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/38 (55.3%) | 18/35 (51.4%) | 9/15 (60%) | 31/61 (50.8%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Hemoglobin decreased | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Cardiac disorders | ||||||||
| Atrial fibrillation | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Myocardial ischemia | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Sinus tachycardia | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Endocrine disorders | ||||||||
| Adrenal insufficiency | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Abdominal pain | 1/38 (2.6%) | 1 | 2/35 (5.7%) | 2 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Colonic fistula | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Colonic perforation | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Constipation | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Diarrhea | 2/38 (5.3%) | 20 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 2/61 (3.3%) | 3 |
| Dry mouth | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Dysphagia | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Intra-abdominal hemorrhage | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Lower gastrointestinal hemorrhage | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Mucositis oral | 2/38 (5.3%) | 5 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 4/61 (6.6%) | 6 |
| Mucositis oral (clin exam) | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Nausea | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Oral pain | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Small intestinal perforation | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Vomiting | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| General disorders | ||||||||
| Chest pain | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 2/61 (3.3%) | 2 |
| Death | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Disease progression | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Edema limbs | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Fatigue | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 2 | 0/15 (0%) | 0 | 2/61 (3.3%) | 3 |
| Infections and infestations | ||||||||
| Infection(gr 0/1/2 ANC) | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Infectious colitis(gr 0/1/2 ANC) | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Opportunistic infection | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Peritoneal infection(gr 0/1/2 ANC) | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Pneumonia(gr 0/1/2 ANC) | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Pneumonia(gr 3/4 ANC) | 2/38 (5.3%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Wound infection(gr 0/1/2 ANC) | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Bruising | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Aspartate aminotransferase increased | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 1/61 (1.6%) | 1 |
| Bilirubin increased | 2/38 (5.3%) | 2 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| CD4 lymphocytes decreased | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Creatinine increased | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Gamma-glutamyltransferase increased | 1/38 (2.6%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Leukocyte count decreased | 2/38 (5.3%) | 5 | 0/35 (0%) | 0 | 1/15 (6.7%) | 2 | 0/61 (0%) | 0 |
| Lipase increased | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Lymphocyte count decreased | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 2/61 (3.3%) | 2 |
| Neutrophil count decreased | 2/38 (5.3%) | 3 | 1/35 (2.9%) | 1 | 2/15 (13.3%) | 4 | 0/61 (0%) | 0 |
| Platelet count decreased | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Weight loss | 9/38 (23.7%) | 11 | 4/35 (11.4%) | 6 | 0/15 (0%) | 0 | 4/61 (6.6%) | 6 |
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Blood glucose increased | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Dehydration | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 3/61 (4.9%) | 3 |
| Serum albumin decreased | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Serum calcium decreased | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 3/61 (4.9%) | 3 |
| Serum calcium increased | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Serum phosphate decreased | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Serum potassium decreased | 2/38 (5.3%) | 3 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Serum potassium increased | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Serum sodium decreased | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 1/15 (6.7%) | 1 | 1/61 (1.6%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 1/38 (2.6%) | 10 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Bone pain | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Muscle weakness | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 2/61 (3.3%) | 3 |
| Myalgia | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Neck pain | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 1/61 (1.6%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Tumor pain | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Nervous system disorders | ||||||||
| Depressed level of consciousness | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Dizziness | 1/38 (2.6%) | 6 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Encephalopathy | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Headache | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Intracranial hemorrhage | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Neurological disorder NOS | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Peripheral sensory neuropathy | 1/38 (2.6%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Speech disorder | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Taste alteration | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 4/61 (6.6%) | 4 |
| Psychiatric disorders | ||||||||
| Agitation | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Anxiety | 0/38 (0%) | 0 | 2/35 (5.7%) | 2 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Confusion | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 3/61 (4.9%) | 3 |
| Depression | 1/38 (2.6%) | 1 | 3/35 (8.6%) | 3 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Libido decreased | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Psychosis | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Renal and urinary disorders | ||||||||
| Protein urine positive | 1/38 (2.6%) | 21 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Ureteric obstruction | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Urethral obstruction | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Urinary incontinence | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Urine discoloration | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Urogenital disorder | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Reproductive tract disorder | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Vaginal hemorrhage | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Adult respiratory distress syndrome | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Cough | 3/38 (7.9%) | 17 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Dyspnea | 0/38 (0%) | 0 | 3/35 (8.6%) | 3 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Hypoxia | 2/38 (5.3%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Laryngeal hemorrhage | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Pharyngolaryngeal pain | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 2/15 (13.3%) | 2 | 0/61 (0%) | 0 |
| Pleuritic pain | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Pneumonitis | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Respiratory disorder | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Hand-and-foot syndrome/reaction | 0/38 (0%) | 0 | 1/35 (2.9%) | 2 | 0/15 (0%) | 0 | 5/61 (8.2%) | 5 |
| Rash desquamating | 1/38 (2.6%) | 15 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Skin hypopigmentation | 2/38 (5.3%) | 20 | 2/35 (5.7%) | 3 | 0/15 (0%) | 0 | 2/61 (3.3%) | 4 |
| Skin ulceration | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Vascular disorders | ||||||||
| Hemorrhage | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Hypertension | 1/38 (2.6%) | 21 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 6/61 (9.8%) | 8 |
| Hypotension | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Thrombosis | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 2/61 (3.3%) | 2 |
Other (Not Including Serious) Adverse Events |
||||||||
| Cohort 1 (DTC) | Cohort 2 (MTC) | Cohort 3 (ATC) | Expansion Cohort (DTC) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 38/38 (100%) | 35/35 (100%) | 15/15 (100%) | 59/61 (96.7%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Hemoglobin decreased | 17/38 (44.7%) | 70 | 14/35 (40%) | 103 | 7/15 (46.7%) | 11 | 33/61 (54.1%) | 182 |
| Cardiac disorders | ||||||||
| Palpitations | 1/38 (2.6%) | 5 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 13 |
| Eye disorders | ||||||||
| Conjunctival disorder | 1/38 (2.6%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Diplopia | 1/38 (2.6%) | 5 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Flashing vision | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Photophobia | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Retinal detachment | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Vision blurred | 2/38 (5.3%) | 3 | 1/35 (2.9%) | 2 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Watering eyes | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 2/38 (5.3%) | 4 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Abdominal pain | 3/38 (7.9%) | 3 | 2/35 (5.7%) | 2 | 0/15 (0%) | 0 | 4/61 (6.6%) | 12 |
| Constipation | 3/38 (7.9%) | 6 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Diarrhea | 28/38 (73.7%) | 294 | 29/35 (82.9%) | 380 | 7/15 (46.7%) | 17 | 48/61 (78.7%) | 505 |
| Dry mouth | 2/38 (5.3%) | 8 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 2/61 (3.3%) | 2 |
| Dyspepsia | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Dysphagia | 2/38 (5.3%) | 4 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Flatulence | 2/38 (5.3%) | 2 | 1/35 (2.9%) | 5 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Lower gastrointestinal hemorrhage | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Mucositis oral | 2/38 (5.3%) | 2 | 1/35 (2.9%) | 6 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Mucositis oral (clin exam) | 1/38 (2.6%) | 3 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Nausea | 29/38 (76.3%) | 166 | 19/35 (54.3%) | 94 | 6/15 (40%) | 11 | 28/61 (45.9%) | 136 |
| Oral hemorrhage | 2/38 (5.3%) | 3 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Oral pain | 3/38 (7.9%) | 4 | 1/35 (2.9%) | 6 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Small intestinal mucositis | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Upper gastrointestinal hemorrhage | 1/38 (2.6%) | 3 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 3/61 (4.9%) | 4 |
| Vomiting | 18/38 (47.4%) | 41 | 9/35 (25.7%) | 31 | 3/15 (20%) | 3 | 20/61 (32.8%) | 71 |
| General disorders | ||||||||
| Chest pain | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Chills | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Edema limbs | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Fatigue | 35/38 (92.1%) | 275 | 29/35 (82.9%) | 286 | 12/15 (80%) | 28 | 50/61 (82%) | 479 |
| Fever | 3/38 (7.9%) | 3 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 2/61 (3.3%) | 2 |
| Flu-like symptoms | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Localized edema | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Pain | 3/38 (7.9%) | 3 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 3/61 (4.9%) | 3 |
| Infections and infestations | ||||||||
| Eye infection | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Infection(gr 0/1/2 ANC) | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Soft tissue infection | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Upper respiratory infection | 1/38 (2.6%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Upper respiratory infectn(gr 0/1/2 ANC) | 2/38 (5.3%) | 3 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Urinary tract infection(gr 0/1/2 ANC) | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 1/61 (1.6%) | 1 |
| Urinary tract infection(gr 3/4 ANC) | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Bruising | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Fracture | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Thermal burn | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase increased | 14/38 (36.8%) | 72 | 4/35 (11.4%) | 16 | 1/15 (6.7%) | 2 | 12/61 (19.7%) | 21 |
| Alkaline phosphatase increased | 6/38 (15.8%) | 8 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Amylase increased | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Aspartate aminotransferase increased | 16/38 (42.1%) | 72 | 15/35 (42.9%) | 72 | 6/15 (40%) | 10 | 30/61 (49.2%) | 97 |
| Bilirubin increased | 8/38 (21.1%) | 20 | 3/35 (8.6%) | 13 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Creatinine increased | 2/38 (5.3%) | 3 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Gamma-glutamyltransferase increased | 1/38 (2.6%) | 17 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 2/61 (3.3%) | 2 |
| Laboratory test abnormal | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Leukocyte count decreased | 16/38 (42.1%) | 51 | 14/35 (40%) | 60 | 4/15 (26.7%) | 11 | 33/61 (54.1%) | 221 |
| Lipase increased | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Lymphocyte count decreased | 1/38 (2.6%) | 1 | 3/35 (8.6%) | 21 | 1/15 (6.7%) | 6 | 6/61 (9.8%) | 19 |
| Neutrophil count decreased | 14/38 (36.8%) | 26 | 8/35 (22.9%) | 27 | 1/15 (6.7%) | 2 | 28/61 (45.9%) | 142 |
| Platelet count decreased | 14/38 (36.8%) | 41 | 10/35 (28.6%) | 38 | 1/15 (6.7%) | 1 | 19/61 (31.1%) | 68 |
| Serum cholesterol increased | 2/38 (5.3%) | 2 | 3/35 (8.6%) | 6 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Weight loss | 12/38 (31.6%) | 75 | 5/35 (14.3%) | 9 | 0/15 (0%) | 0 | 6/61 (9.8%) | 44 |
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 23/38 (60.5%) | 93 | 20/35 (57.1%) | 91 | 8/15 (53.3%) | 14 | 28/61 (45.9%) | 133 |
| Blood glucose increased | 5/38 (13.2%) | 18 | 3/35 (8.6%) | 8 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Blood uric acid increased | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Dehydration | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Serum albumin decreased | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 2/61 (3.3%) | 3 |
| Serum calcium decreased | 1/38 (2.6%) | 1 | 2/35 (5.7%) | 2 | 0/15 (0%) | 0 | 2/61 (3.3%) | 2 |
| Serum calcium increased | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Serum magnesium decreased | 0/38 (0%) | 0 | 1/35 (2.9%) | 3 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Serum magnesium increased | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 1/15 (6.7%) | 3 | 0/61 (0%) | 0 |
| Serum potassium decreased | 1/38 (2.6%) | 2 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Serum potassium increased | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Serum sodium decreased | 1/38 (2.6%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Serum triglycerides increased | 5/38 (13.2%) | 21 | 2/35 (5.7%) | 5 | 0/15 (0%) | 0 | 2/61 (3.3%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthritis | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Back pain | 2/38 (5.3%) | 7 | 2/35 (5.7%) | 3 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Bone pain | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Chest wall pain | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Joint disorder | 1/38 (2.6%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Joint pain | 3/38 (7.9%) | 6 | 3/35 (8.6%) | 10 | 1/15 (6.7%) | 1 | 2/61 (3.3%) | 4 |
| Muscle weakness | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Muscle weakness lower limb | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Myalgia | 6/38 (15.8%) | 11 | 3/35 (8.6%) | 7 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Neck pain | 1/38 (2.6%) | 3 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Pain in extremity | 1/38 (2.6%) | 4 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 3 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Tumor pain | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 2/61 (3.3%) | 2 |
| Nervous system disorders | ||||||||
| Dizziness | 2/38 (5.3%) | 2 | 1/35 (2.9%) | 1 | 1/15 (6.7%) | 1 | 1/61 (1.6%) | 1 |
| Extrapyramidal disorder | 1/38 (2.6%) | 3 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Headache | 5/38 (13.2%) | 7 | 2/35 (5.7%) | 2 | 0/15 (0%) | 0 | 4/61 (6.6%) | 6 |
| Neuralgia | 1/38 (2.6%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Olfactory nerve disorder | 1/38 (2.6%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Peripheral sensory neuropathy | 7/38 (18.4%) | 31 | 8/35 (22.9%) | 42 | 0/15 (0%) | 0 | 12/61 (19.7%) | 40 |
| Taste alteration | 22/38 (57.9%) | 128 | 5/35 (14.3%) | 19 | 2/15 (13.3%) | 2 | 9/61 (14.8%) | 33 |
| Psychiatric disorders | ||||||||
| Agitation | 0/38 (0%) | 0 | 4/35 (11.4%) | 9 | 1/15 (6.7%) | 2 | 5/61 (8.2%) | 5 |
| Anxiety | 0/38 (0%) | 0 | 7/35 (20%) | 26 | 1/15 (6.7%) | 1 | 7/61 (11.5%) | 25 |
| Depression | 2/38 (5.3%) | 3 | 5/35 (14.3%) | 31 | 0/15 (0%) | 0 | 8/61 (13.1%) | 28 |
| Euphoria | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 3 |
| Insomnia | 4/38 (10.5%) | 9 | 2/35 (5.7%) | 4 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Libido decreased | 0/38 (0%) | 0 | 1/35 (2.9%) | 6 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Psychosis | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Renal and urinary disorders | ||||||||
| Kidney pain | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Protein urine positive | 10/38 (26.3%) | 79 | 15/35 (42.9%) | 27 | 8/15 (53.3%) | 10 | 27/61 (44.3%) | 121 |
| Urinary frequency | 3/38 (7.9%) | 3 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Vaginal hemorrhage | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Vaginal mucositis | 1/38 (2.6%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 3/38 (7.9%) | 5 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 2/61 (3.3%) | 4 |
| Dyspnea | 0/38 (0%) | 0 | 1/35 (2.9%) | 2 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Hemorrhage nasal | 6/38 (15.8%) | 6 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Laryngeal hemorrhage | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Laryngeal pain | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Nasal congestion | 0/38 (0%) | 0 | 1/35 (2.9%) | 4 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Pharyngeal mucositis | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 11 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Pharyngolaryngeal pain | 2/38 (5.3%) | 4 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Pulmonary fistula | 0/38 (0%) | 0 | 1/35 (2.9%) | 1 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Respiratory tract hemorrhage | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Voice alteration | 3/38 (7.9%) | 14 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 13/38 (34.2%) | 79 | 2/35 (5.7%) | 8 | 0/15 (0%) | 0 | 3/61 (4.9%) | 13 |
| Dry skin | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 7 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Hand-and-foot syndrome/reaction | 2/38 (5.3%) | 3 | 3/35 (8.6%) | 6 | 0/15 (0%) | 0 | 8/61 (13.1%) | 10 |
| Nail disorder | 2/38 (5.3%) | 7 | 1/35 (2.9%) | 8 | 0/15 (0%) | 0 | 1/61 (1.6%) | 5 |
| Pain of skin | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Petechiae | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Pruritus | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Rash desquamating | 5/38 (13.2%) | 9 | 1/35 (2.9%) | 4 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
| Skin disorder | 1/38 (2.6%) | 4 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 4 |
| Skin hyperpigmentation | 1/38 (2.6%) | 10 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Skin hypopigmentation | 28/38 (73.7%) | 337 | 22/35 (62.9%) | 339 | 5/15 (33.3%) | 10 | 42/61 (68.9%) | 490 |
| Sweating | 1/38 (2.6%) | 1 | 1/35 (2.9%) | 1 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Vascular disorders | ||||||||
| Flushing | 2/38 (5.3%) | 2 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Hemorrhage | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 3 |
| Hot flashes | 2/38 (5.3%) | 14 | 0/35 (0%) | 0 | 1/15 (6.7%) | 1 | 0/61 (0%) | 0 |
| Hypertension | 21/38 (55.3%) | 81 | 20/35 (57.1%) | 239 | 8/15 (53.3%) | 10 | 46/61 (75.4%) | 497 |
| Hypotension | 1/38 (2.6%) | 1 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 0/61 (0%) | 0 |
| Thrombosis | 0/38 (0%) | 0 | 0/35 (0%) | 0 | 0/15 (0%) | 0 | 1/61 (1.6%) | 2 |
Limitations/Caveats
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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Keith C. Bible, M.D., Ph.D. |
|---|---|
| Organization | Mayo Clinic |
| Phone | 507-284-2511 |
| bible.keith@mayo.edu |
- NCI-2009-00198
- NCI-2009-00198
- MC057H
- CDR0000588044
- 7627
- 7627
- N01CM00099
- N01CM62205
- P30CA015083
- NCT01648387
- NCT02653053