Trial Outcomes & Findings for An Open Label Phase I Dose Escalation Study of E7080 Administered to Patients With Solid Tumors (NCT NCT00280397)

NCT ID: NCT00280397

Last Updated: 2016-10-07

Results Overview

The MTD was defined as the highest dose at which no dose limiting toxicity (DLT) was experienced by the first 3 patients in that cohort, or the dose at which a DLT was experienced by no more than 1 of 6 patients evaluable for toxicity.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 27 participants
• Primary outcome timeframe: up to 4 weeks
• Results posted on: 2016-10-07

Participant Flow

Participant milestones

Measure	E7080 Group E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.
Overall Study STARTED	27
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	E7080 Group E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.
Overall Study Adverse Event	1

Baseline Characteristics

An Open Label Phase I Dose Escalation Study of E7080 Administered to Patients With Solid Tumors

Baseline characteristics by cohort

Measure	E7080 Group n=27 Participants E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.
Age, Continuous	50.7 Years STANDARD_DEVIATION 11.1 • n=5 Participants
Sex/Gender, Customized Male	10 Participants n=5 Participants
Sex/Gender, Customized Female	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 4 weeks

Population: Registered participants were included in the tolerability analysis set with the exception of the ineligible participants, participants with a treatment compliance rate of less than 75%, and participants who discontinued the study for reasons other than occurrence of DLT. However, cases of DLT shall be included in analyses.

The MTD was defined as the highest dose at which no dose limiting toxicity (DLT) was experienced by the first 3 patients in that cohort, or the dose at which a DLT was experienced by no more than 1 of 6 patients evaluable for toxicity.

Outcome measures

Measure	E7080 Group n=26 Participants E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.	E7080 - 20 mg Group E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.
Maximum Tolerable Dose (MTD) of E7080 Repeatedly Administered Twice a Day	13 mg BID	—

PRIMARY outcome

Timeframe: up to 4 weeks

Population: Registered participants were included in the tolerability analysis set with the exception of the ineligible participants, participants with a treatment compliance rate of less than 75%, and participants who discontinued the study for reasons other than occurrence of DLT. However, cases of DLT shall be included in analyses.

DLTs were defined as grade 3 or more platelet count decrease, grade 4 neutropenia, any grade 3 or more nonhematologic toxicity (with exceptions of grade 4 hypertension not controlled by any antihypertensive drugs and grade greater than or equal to 3 vomiting and diarrhea not controlled by antiemetic or antidiarrheal drugs), and failure to administer more than 75% of the planned doses of E7080 during the same cycle due to toxicity.

Outcome measures

Measure	E7080 Group n=3 Participants E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.	E7080 - 20 mg Group n=3 Participants E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.
DLT of E7080 Repeatedly Administered Twice a Day	1 Participants with DLT	2 Participants with DLT

SECONDARY outcome

Timeframe: Every 3 weeks

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons.

Population: All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses.

Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.

Outcome measures

Measure	E7080 Group n=27 Participants E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.	E7080 - 20 mg Group E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.
Number of Participants With Adverse Events / Serious Adverse Events	27 Participants	—

SECONDARY outcome

Timeframe: Every 3 weeks

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 3 weeks

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 3 weeks

Outcome measures

Outcome data not reported

Adverse Events

E7080 Group

Serious events: 7 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	E7080 Group n=27 participants at risk E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.
Vascular disorders Hypertension	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Renal and urinary disorders Postrenal failure	3.7% 1/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Vascular disorders Haemorrhage	3.7% 1/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Infections and infestations Pneumonia	3.7% 1/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.7% 1/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Platelet count decreased	3.7% 1/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Injury, poisoning and procedural complications Humerus fracture	3.7% 1/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.

Other adverse events

Measure	E7080 Group n=27 participants at risk E7080 is administered orally twice a day for 2 weeks to patients with solid tumors that are resistant to approved conventional therapies or for which no appropriate treatment is available.
Blood and lymphatic system disorders Anaemia	22.2% 6/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Cardiac disorders Sinus bradycardia	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Eye disorders Eyelid oedema	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Gastrointestinal disorders Abdominal pain	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Gastrointestinal disorders Abdominal pain upper	18.5% 5/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Gastrointestinal disorders Constipation	25.9% 7/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Gastrointestinal disorders Diarrhoea	55.6% 15/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Gastrointestinal disorders Gingival bleeding	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Gastrointestinal disorders Gingivitis	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Gastrointestinal disorders Nausea	44.4% 12/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Gastrointestinal disorders Stomach discomfort	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Gastrointestinal disorders Stomatitis	18.5% 5/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Gastrointestinal disorders Vomiting	29.6% 8/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
General disorders Chest pain	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
General disorders Face oedema	14.8% 4/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
General disorders Fatigue	70.4% 19/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
General disorders Malaise	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
General disorders Oedema	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
General disorders Oedema peripheral	37.0% 10/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
General disorders Pyrexia	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Infections and infestations Nasopharyngitis	33.3% 9/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Infections and infestations Tonsillitis	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Injury, poisoning and procedural complications Procedural pain	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Alanine aminotransferase increased	55.6% 15/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Aspartate aminotransferase increased	63.0% 17/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood albumin decreased	48.1% 13/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood alkaline phosphatase increased	48.1% 13/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood bilirubin increased	14.8% 4/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood calcium decreased	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood cholesterol increased	18.5% 5/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood creatine phosphokinase increased	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood creatinine increased	25.9% 7/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood fibrinogen increased	37.0% 10/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood lactate dehydrogenase increased	51.9% 14/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood potassium increased	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood sodium decreased	14.8% 4/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood thyroid stimulating hormone increased	25.9% 7/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood triglycerides increased	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood urea increased	25.9% 7/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood uric acid increased	14.8% 4/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Blood urine present	74.1% 20/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations C-reactive protein increased	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Electrocardiogram T wave amplitude decreased	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Gamma-glutamyltransferase increased	40.7% 11/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Glucose urine present	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Haemoglobin decreased	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Leucine aminopeptidase increased	14.8% 4/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Lymphocyte count decreased	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Neutrophil count decreased	18.5% 5/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Neutrophil count increased	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Platelet count decreased	37.0% 10/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Platelet count increased	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Protein total decreased	33.3% 9/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Protein urine present	63.0% 17/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Red blood cell count decreased	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Weight decreased	14.8% 4/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations Weight increased	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations White blood cell count decreased	25.9% 7/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Investigations White blood cell count increased	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Metabolism and nutrition disorders Anorexia	44.4% 12/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Metabolism and nutrition disorders Hypercholesterolaemia	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Metabolism and nutrition disorders Hyperlipidaemia	22.2% 6/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Musculoskeletal and connective tissue disorders Arthralgia	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Musculoskeletal and connective tissue disorders Back pain	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Musculoskeletal and connective tissue disorders Myalgia	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Musculoskeletal and connective tissue disorders Pain in extremity	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Nervous system disorders Dizziness	22.2% 6/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Nervous system disorders Headache	63.0% 17/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Psychiatric disorders Insomnia	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Renal and urinary disorders Haematuria	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Respiratory, thoracic and mediastinal disorders Cough	14.8% 4/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Respiratory, thoracic and mediastinal disorders Dysphonia	14.8% 4/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.2% 6/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Respiratory, thoracic and mediastinal disorders Epistaxis	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Respiratory, thoracic and mediastinal disorders Haemoptysis	11.1% 3/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Skin and subcutaneous tissue disorders Dermatitis acneiform	7.4% 2/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	18.5% 5/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	14.8% 4/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Skin and subcutaneous tissue disorders Rash	18.5% 5/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Vascular disorders Hot flush	14.8% 4/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.
Vascular disorders Hypertension	63.0% 17/27 • Until tumor progression, unacceptable toxicity, or withdrawal due to other reasons. All participants who received at least one E7080 dose and had evaluable data were included in the safety analyses. Treatment emergent adverse events (AEs) and serious adverse events (SAEs) were evaluated.

Additional Information

Akihiko Tsuruoka

Eisai Co., Ltd.

Phone: +81-3-3817-5252

Results disclosure agreements

• Principal investigator is a sponsor employee Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.
• Publication restrictions are in place

Restriction type: OTHER