Trial Outcomes & Findings for Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas (NCT NCT00030264)

Last Updated: 2018-08-08

Results Overview

Disease progression was assessed both radiographically and clinically. Tumor assessments to assess for radiographic disease progression were assessed by magnetic resonance imaging (MRI) measurement whenever possible or computed tomography (CT) scan and/or tumor measurement during physical examination of palpable lesions. Clinical assessments for clinical progression of disease were assessed by treating physician or designee. Progressive disease as measured by the appearance of new lesions; an increased size of index tumor(s) by \>/= 25% of the sum of the products of baseline measurements; and/or by increase in symptoms.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

6 months

Results posted on

2018-08-08

Participant Flow

23 eligible subjects were enrolled at the Children's Hospital of Philadelphia and Texas Children's Hospital between March 2001 and June 2011

Participant milestones

Participant milestones
Measure	Methotrexate & Vinblastine Methotrexate and Vinblastine will be given once a week for the first 26 weeks and then every two weeks for the next 26 weeks or until disease progression (whichever occurs first). Methotrexate: Methotrexate will be given at a dose of 30mg/m2/week intramuscular (IM) or intravenous (IV) for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first) Vinblastine: Vinblastine will be given at a dose of 6mg/m2/week intravenous (IV) for for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first). Maximum actual dose may not exceed 10mg.
Overall Study STARTED	23
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methotrexate & Vinblastine n=23 Participants Methotrexate and Vinblastine will be given once a week for the first 26 weeks and then every two weeks for the next 26 weeks or until disease progression (whichever occurs first). Methotrexate: Methotrexate will be given at a dose of 30mg/m2/week intramuscular (IM) or intravenous (IV) for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first) Vinblastine: Vinblastine will be given at a dose of 6mg/m2/week intravenous (IV) for for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first). Maximum actual dose may not exceed 10mg.
Age, Categorical <=18 years	19 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	5.56 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: 20 subjects were analyzed for time to progression. 3 subjects were not included in the response analysis due to lost to follow up (N=2) or progression of comorbid condition which required early termination (N=1)

Outcome measures

Outcome measures
Measure	Methotrexate & Vinblastine n=20 Participants Methotrexate and Vinblastine will be given once a week for the first 26 weeks and then every two weeks for the next 26 weeks or until disease progression (whichever occurs first). Methotrexate: Methotrexate will be given at a dose of 30mg/m2/week intramuscular (IM) or intravenous (IV) for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first) Vinblastine: Vinblastine will be given at a dose of 6mg/m2/week intravenous (IV) for for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first). Maximum actual dose may not exceed 10mg.
Time to Disease Progression Total	25.8 Months Interval 0.2 to 85.0
Time to Disease Progression Radiographic Progression	29.2 Months Interval 3.1 to 58.5
Time to Disease Progression Clinical Progression	25.8 Months Interval 0.2 to 85.0

Adverse Events

Methotrexate & Vinblastine

Serious events: 6 serious events

Other events: 8 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Methotrexate & Vinblastine n=23 participants at risk Methotrexate and Vinblastine will be given once a week for the first 26 weeks and then every two weeks for the next 26 weeks or until disease progression (whichever occurs first). Methotrexate: Methotrexate will be given at a dose of 30mg/m2/week intramuscular (IM) or intravenous (IV) for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first) Vinblastine: Vinblastine will be given at a dose of 6mg/m2/week intravenous (IV) for for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first). Maximum actual dose may not exceed 10mg.
Infections and infestations Infection - Bacterial	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.
Hepatobiliary disorders Hepatic - Other - Cholecytitis	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.
Gastrointestinal disorders Anorexia	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.
Respiratory, thoracic and mediastinal disorders Pulmonary - Other - Respiratory Distress	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.
Infections and infestations Infection - Viral	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.
Investigations Febrile neutropenia	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.
Investigations Fever	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.
Infections and infestations Infection	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.

Other adverse events

Other adverse events
Measure	Methotrexate & Vinblastine n=23 participants at risk Methotrexate and Vinblastine will be given once a week for the first 26 weeks and then every two weeks for the next 26 weeks or until disease progression (whichever occurs first). Methotrexate: Methotrexate will be given at a dose of 30mg/m2/week intramuscular (IM) or intravenous (IV) for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first) Vinblastine: Vinblastine will be given at a dose of 6mg/m2/week intravenous (IV) for for the first 26 weeks, then every 2 weeks for the next 26 weeks or until disease progression (whichever occurs first). Maximum actual dose may not exceed 10mg.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	34.8% 8/23 • Number of events 15 For non-serious events, CTCAE Grade 3 and 4 were collected.
Blood and lymphatic system disorders Leukocytes (total WBC)	8.7% 2/23 • Number of events 3 For non-serious events, CTCAE Grade 3 and 4 were collected.
Blood and lymphatic system disorders Lymphopenia	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.
Infections and infestations Infection - Viral	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.
Investigations SGPT (ALT) (serum glutamic pyruvic transaminase)	4.3% 1/23 • Number of events 1 For non-serious events, CTCAE Grade 3 and 4 were collected.

Additional Information

Ratnakar Patti

Children's Hospital of Philadelphia

Phone: 267-426-5503

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place