Trial Outcomes & Findings for RAPAMYCIN FOR KIDNEY ANGIOMYOLIPOMAS (NCT NCT00126672)

Last Updated: 2022-04-25

Results Overview

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

On treatment, patients were evaluated radiologically for response to therapy up to 52 weeks.

Results posted on

2022-04-25

Participant Flow

Participant milestones

Participant milestones
Measure	Rapamycin After the screening procedures confirm that you are eligible to participate in the research study * Rapamycin: oral, 3-9 ng/ml daily for 4 months, then increase dose to 9-15 ng/ml for 20 months. * MRI/CT scan at 16 week, 32 weeks, 52 weeks during treatments.
Overall Study STARTED	36
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Rapamycin After the screening procedures confirm that you are eligible to participate in the research study * Rapamycin: oral, 3-9 ng/ml daily for 4 months, then increase dose to 9-15 ng/ml for 20 months. * MRI/CT scan at 16 week, 32 weeks, 52 weeks during treatments.
Overall Study Adverse Event	4
Overall Study Lost to Follow-up	4

Baseline Characteristics

RAPAMYCIN FOR KIDNEY ANGIOMYOLIPOMAS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramaycin n=36 Participants After the screening procedures confirm that you are eligible to participate in the research study * Rapamycin: oral, 3-9 ng/ml daily for 4 months, then increase dose to 9-15 ng/ml for 20 months. * MRI/CT scan at 16 week, 32 weeks, 52 weeks during treatments.
Age, Continuous	34 years n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Race/Ethnicity, Customized White	34 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Region of Enrollment United States	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: On treatment, patients were evaluated radiologically for response to therapy up to 52 weeks.

Outcome measures

Outcome measures
Measure	Ramaycin n=36 Participants After the screening procedures confirm that you are eligible to participate in the research study * Rapamycin: oral, 3-9 ng/ml daily for 4 months, then increase dose to 9-15 ng/ml for 20 months. * MRI/CT scan at 16 week, 32 weeks, 52 weeks during treatments.
Objective Response Rate	44.4 percentage of participants Interval 28.0 to 61.0

SECONDARY outcome

Timeframe: Assessed on treatment up to 52 weeks.

All participants reporting maximum grade 3 or more lymphopenia adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv3 on case report forms were counted.

Outcome measures

Outcome measures
Measure	Ramaycin n=36 Participants After the screening procedures confirm that you are eligible to participate in the research study * Rapamycin: oral, 3-9 ng/ml daily for 4 months, then increase dose to 9-15 ng/ml for 20 months. * MRI/CT scan at 16 week, 32 weeks, 52 weeks during treatments.
Number of Participants With Grade 3 or More Treatment-Related Lymphopenia	1 Participants

SECONDARY outcome

Timeframe: Data collected at week 52

TSC lesions are tubers, subependymal giant cell astrocytomas, facial angiofibromas, kidney cysts.

Outcome measures

Outcome measures
Measure	Ramaycin n=36 Participants After the screening procedures confirm that you are eligible to participate in the research study * Rapamycin: oral, 3-9 ng/ml daily for 4 months, then increase dose to 9-15 ng/ml for 20 months. * MRI/CT scan at 16 week, 32 weeks, 52 weeks during treatments.
Number of Participants With no Change Are Observed Changes That Occur in Other TSC Lesions	0 Participants

Adverse Events

Ramaycin

Serious events: 36 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ramaycin n=36 participants at risk After the screening procedures confirm that you are eligible to participate in the research study * Rapamycin: oral, 3-9 ng/ml daily for 4 months, then increase dose to 9-15 ng/ml for 20 months. * MRI/CT scan at 16 week, 32 weeks, 52 weeks during treatments.
Blood and lymphatic system disorders Anemia	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Blood and lymphatic system disorders Febrile neutropenia	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastric ulcer	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Mucositis oral	13.9% 5/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Alanine aminotransferase increased	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Alkaline phosphatase increased	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Neutrophil count decreased	88.9% 32/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Platelet count decreased	13.9% 5/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations White blood cell decreased	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyperglycemia	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypokalemia	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Other adverse events

Other adverse events
Measure	Ramaycin n=36 participants at risk After the screening procedures confirm that you are eligible to participate in the research study * Rapamycin: oral, 3-9 ng/ml daily for 4 months, then increase dose to 9-15 ng/ml for 20 months. * MRI/CT scan at 16 week, 32 weeks, 52 weeks during treatments.
Blood and lymphatic system disorders Anemia	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Cardiac disorders Sinus tachycardia	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Endocrine disorders Endocrine disorders - Other, specify	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Abdominal pain	11.1% 4/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Constipation	11.1% 4/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Diarrhea	27.8% 10/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dry mouth	11.1% 4/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Dyspepsia	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Enterocolitis	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Flatulence	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Hemorrhoids	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Jejunal hemorrhage	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Lip pain	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Mucositis oral	100.0% 36/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Nausea	36.1% 13/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Oral pain	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Stomach pain	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Toothache	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Gastrointestinal disorders Vomiting	13.9% 5/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Chills	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Edema limbs	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Fatigue	72.2% 26/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Fever	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Gait disturbance	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
General disorders Pain	11.1% 4/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Immune system disorders Allergic reaction	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Lung infection	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Sinusitis	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Tooth infection	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Upper respiratory infection	11.1% 4/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Infections and infestations Urinary tract infection	11.1% 4/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Alanine aminotransferase increased	22.2% 8/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Alkaline phosphatase increased	11.1% 4/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Aspartate aminotransferase increased	19.4% 7/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Blood bilirubin increased	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Creatinine increased	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Investigations - Other, specify	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Lymphocyte count decreased	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Neutrophil count decreased	100.0% 36/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Platelet count decreased	61.1% 22/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations Weight loss	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Investigations White blood cell decreased	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Anorexia	22.2% 8/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Dehydration	11.1% 4/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyperglycemia	16.7% 6/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypoglycemia	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hypokalemia	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Metabolism and nutrition disorders Hyponatremia	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Back pain	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Neck pain	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Musculoskeletal and connective tissue disorders Pain in extremity	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Brachial plexopathy	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Dysgeusia	22.2% 8/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Headache	30.6% 11/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Nervous system disorders Peripheral sensory neuropathy	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Anxiety	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Depression	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Psychiatric disorders Insomnia	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Urinary frequency	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Renal and urinary disorders Urinary incontinence	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Reproductive system and breast disorders Breast pain	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Reproductive system and breast disorders Vaginal dryness	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Cough	13.9% 5/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Dyspnea	25.0% 9/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Epistaxis	25.0% 9/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Hiccups	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Pneumonitis	30.6% 11/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Respiratory, thoracic and mediastinal disorders Tracheal fistula	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Alopecia	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Dry skin	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Pruritus	8.3% 3/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash acneiform	30.6% 11/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hot flashes	5.6% 2/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Vascular disorders Hypertension	2.8% 1/36 • Assessed at 16, 32 and 52 weeks and up to day 30 post-treatment. Treatment duration average (including first 52 weeks) was 78 weeks, range 60-100 weeks. Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Additional Information

Dabora Sandra L MD

Dana-Farber Cancer Institute

Phone: (617) 732-5500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place