Trial Outcomes & Findings for Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas (NCT NCT00782626)

Last Updated: 2018-08-15

Results Overview

Overall response is classified as complete response (CR), partial response (PR), stable disease (SD) or Progressive Disease (PD) on therapy.Description: Overall response is classified as complete response (CR), partial response (PR), stable disease (SD) or Progressive Disease (PD) on therapy. Response for target lesions (up to5) is based on 3 dimensions with an elliptical model volume used: 0.5L\*W\*T; (L) tumor extent in plane perpendicular to the selected plane; (W) longest measurement of the tumor width; (T) transverse measurement perpendicular to the width. CR is disappearance all target and non-target lesions and no new lesions. PR is \>/= 65% decrease in sum of the products (referent baseline). PD 40% or more increase in any target lesion (referent smallest product observed on therapy). SD is none of the above. PR and SD classification as long as absent new lesions and unequivocal progression for non-target lesions else PD.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Disease evaluations (MRI brain, including volumetric analysis) occurred at baseline, at the end of course 1, every 3 courses during treatment up to 12 courses and at early treatment discontinuation.

Results posted on

2018-08-15

Participant Flow

Pts enrolled from 9 institutions over a two-year period (9/2009-9/2011).

Participant milestones

Participant milestones
Measure	Everolimus Patients rcvd oral everolimus 5.0 mg/m2/day for a 28-day treatment course up to a total of 12 courses (48 weeks) if a patient had stable disease except if toxicity was unacceptable. Two dose reductions were permitted (3.0 5.0 mg/m2/day and 2.0 mg/m2/day).
Overall Study STARTED	23
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus Patients rcvd oral everolimus 5.0 mg/m2/day for a 28-day treatment course up to a total of 12 courses (48 weeks) if a patient had stable disease except if toxicity was unacceptable. Two dose reductions were permitted (3.0 5.0 mg/m2/day and 2.0 mg/m2/day).
Overall Study Adverse Event	1
Overall Study Progressive Disease	5
Overall Study Other Complicating Disease	1

Baseline Characteristics

Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus n=23 Participants Patients rcvd oral everolimus 5.0 mg/m2/day for a 28-day treatment course up to a total of 12 courses (48 weeks) if a patient had stable disease except if toxicity was unacceptable. Two dose reductions were permitted (3.0 5.0 mg/m2/day and 2.0 mg/m2/day).
Age, Categorical <=18 years	23 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	9 years n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants

PRIMARY outcome

Timeframe: Disease evaluations (MRI brain, including volumetric analysis) occurred at baseline, at the end of course 1, every 3 courses during treatment up to 12 courses and at early treatment discontinuation.

Population: The analysis dataset is comprised of all evaluable patients. All treated patients were evaluable.

Outcome measures

Outcome measures
Measure	Everolimus n=23 Participants Patients rcvd oral everolimus 5.0 mg/m2/day for a 28-day treatment course up to a total of 12 courses (48 weeks) if a patient had stable disease except if toxicity was unacceptable. Two dose reductions were permitted (3.0 5.0 mg/m2/day and 2.0 mg/m2/day).
Overall Response Partial Response	2 participants
Overall Response Stable Disease	21 participants

Adverse Events

Everolimus

Serious events: 6 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Everolimus n=23 participants at risk Patients rcvd oral everolimus 5.0 mg/m2/day for a 28-day treatment course up to a total of 12 courses (48 weeks) if a patient had stable disease except if toxicity was unacceptable. Two dose reductions were permitted (3.0 5.0 mg/m2/day and 2.0 mg/m2/day).
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Vomiting	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
General disorders Fatigue	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Infections and infestations Infection-other	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Injury, poisoning and procedural complications Vascular access,Thrombosis/embolism	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations Neutrophils	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations ALT, SGPT	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations AST, SGOT	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Anorexia	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hypokalemia	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.

Other adverse events

Other adverse events
Measure	Everolimus n=23 participants at risk Patients rcvd oral everolimus 5.0 mg/m2/day for a 28-day treatment course up to a total of 12 courses (48 weeks) if a patient had stable disease except if toxicity was unacceptable. Two dose reductions were permitted (3.0 5.0 mg/m2/day and 2.0 mg/m2/day).
Blood and lymphatic system disorders Hemoglobin	26.1% 6/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Cardiac disorders Sinus bradycardia	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Cardiac disorders Sinus tachycardia	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Ear and labyrinth disorders Middle ear, pain	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Endocrine disorders Hyopthyroidism	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Eye disorders Ocular-other	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Constipation	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Diarrhea w/o prior colostomy	34.8% 8/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Distention/bloating, abdominal	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Flatulence	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	52.2% 12/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Muco/stomatitis (symptom) oral cavity	13.0% 3/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Nausea	52.2% 12/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Vomiting	26.1% 6/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders GI-other	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Abdomen, pain	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Oral cavity, pain	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Gastrointestinal disorders Stomach, pain	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
General disorders Fatigue	30.4% 7/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
General disorders Fever w/o neutropenia	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
General disorders Pain-other	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Infections and infestations Infection-other	13.0% 3/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Injury, poisoning and procedural complications Bruising	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations Leukocytes	39.1% 9/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations Lymphopenia	26.1% 6/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations Neutrophils	26.1% 6/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations Platelets	43.5% 10/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations Alkaline phosphatase	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations ALT, SGPT	13.0% 3/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations AST, SGOT	17.4% 4/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Investigations Hypercholesterolemia	82.6% 19/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Anorexia	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Dehydration	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hypoalbuminemia	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Bicarbonate	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hypercalcemia	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hyperglycemia	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hypermagnesemia	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hypophosphatemia	13.0% 3/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hyperkalemia	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hypokalemia	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hypernatremia	13.0% 3/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hyponatremia	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hypertriglyceridemia	30.4% 7/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Metabolism and nutrition disorders Hyperuricemia	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Musculoskeletal and connective tissue disorders Nonneuropathic generalized weakness	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Musculoskeletal and connective tissue disorders Extremity-limb, pain	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Musculoskeletal and connective tissue disorders Neck, pain	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Nervous system disorders Dizziness	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Nervous system disorders Neurologic-other	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Nervous system disorders Head/headache	21.7% 5/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Respiratory, thoracic and mediastinal disorders Cough	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory-other	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Skin and subcutaneous tissue disorders Pruritus/itching	13.0% 3/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Skin and subcutaneous tissue disorders Rash/desquamation	8.7% 2/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Skin and subcutaneous tissue disorders Hand-foot reaction	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
Vascular disorders Hypertension	4.3% 1/23 • Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Patients received up to 48 weeks of treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.

Additional Information

Mark Kieran

Dana-Farber Cancer Institute

Phone: (617) 632-4907

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place