Trial Outcomes & Findings for Selumetinib in Treating Patients With Neurofibromatosis Type 1 and Cutaneous Neurofibroma (NCT NCT02839720)

Last Updated: 2023-12-06

Results Overview

Average percent change in volume of target cutaneous neurofibromas from baseline. Cutaneous neurofibromas measured with calipers and volumes calculated by multiplying length, width and height of each target neurofibroma. At each response evaluation (baseline and then after every 4 cycles), the sum of the on-treatment volumes for the target cutaneous neurofibromas were subtracted from the pre-treatment volumes of the same tumors to arrive at an overall percentage change in target cutaneous neurofibroma size for each participant at each restaging evaluation. The average percent change that was most decreased from baseline (best response) for each participant was collected and the timepoint at which this occurred was noted. The median and range of these average percent change best responses are reported here.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Up to 24 cycles of treatment (1 cycle = 28 days)

Results posted on

2023-12-06

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Selumetinib) Participants receive selumetinib capsules at a dose of 50mg by mouth (PO) twice daily (BID) every 12 hours with option to increase to 75mg PO BID after first cycle if tolerated. Treatment repeats every 28 days (1 cycle = 28 days) for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Participants who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles. Volume decrease defined as a greater than or equal to 20 percent decrease in the sum of the volumes of the smaller and/or larger target cutaneous neurofibromas.
Overall Study STARTED	11
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Selumetinib) Participants receive selumetinib capsules at a dose of 50mg by mouth (PO) twice daily (BID) every 12 hours with option to increase to 75mg PO BID after first cycle if tolerated. Treatment repeats every 28 days (1 cycle = 28 days) for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Participants who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles. Volume decrease defined as a greater than or equal to 20 percent decrease in the sum of the volumes of the smaller and/or larger target cutaneous neurofibromas.
Overall Study Adverse Event	2
Overall Study Non-compliance	2
Overall Study Intercurrent Illness	1
Overall Study Non-compliance due to COVID-19 pandemic	2

Baseline Characteristics

Selumetinib in Treating Patients With Neurofibromatosis Type 1 and Cutaneous Neurofibroma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Selumetinib) n=11 Participants Participants receive selumetinib capsules at a dose of 50mg by mouth (PO) twice daily (BID) every 12 hours with option to increase to 75mg PO BID after first cycle if tolerated. Treatment repeats every 28 days (1 cycle = 28 days) for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Participants who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles. Volume decrease defined as a greater than or equal to 20 percent decrease in the sum of the volumes of the smaller and/or larger target cutaneous neurofibromas.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Age, Continuous	54 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 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	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants
Average cutaneous neurofibroma (cNF) volume	159.1 microliters n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 cycles of treatment (1 cycle = 28 days)

Population: Includes all participants who had at least one restaging evaluation on treatment with selumetinib

Outcome measures

Outcome measures
Measure	Treatment (Selumetinib) n=8 Participants Participants receive selumetinib capsules at a dose of 50mg by mouth (PO) twice daily (BID) every 12 hours with option to increase to 75mg PO BID after first cycle if tolerated. Treatment repeats every 28 days (1 cycle = 28 days) for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Participants who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles. Volume decrease defined as a greater than or equal to 20 percent decrease in the sum of the volumes of the smaller and/or larger target cutaneous neurofibromas.
Median Best Response of Cutaneous Neurofibromas in Participants With at Least One Restaging Evaluation	-28.5 percent change Interval -84.9 to 24.8

SECONDARY outcome

Timeframe: Baseline to up to 1 year

Population: Includes all participants that completed 12 cycles of selumetinib.

At the time of each response evaluation (baseline and then after every 4 cycles), the number of cutaneous neurofibromas (cNFs) that are greater than 4mm as measured with a caliper were counted in the picture frames. We report here the change in overall number of cutaneous neurofibromas counted after 12 cycles of treatment (Number of cNFs counted after 12 cycles - Number of cNFs counted at baseline).

Outcome measures

Outcome measures
Measure	Treatment (Selumetinib) n=5 Participants Participants receive selumetinib capsules at a dose of 50mg by mouth (PO) twice daily (BID) every 12 hours with option to increase to 75mg PO BID after first cycle if tolerated. Treatment repeats every 28 days (1 cycle = 28 days) for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Participants who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles. Volume decrease defined as a greater than or equal to 20 percent decrease in the sum of the volumes of the smaller and/or larger target cutaneous neurofibromas.
Change in the Number of Cutaneous Neurofibromas	-7 neurofibromas Interval -30.0 to 4.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 1 year

Population: Only included analysis of the 5 participants who had baseline and 1 year on treatment Overall SkinDex scores available.

Assessed by Skindex. Global Impression of Change Scale and Numeric Rating Scale evaluations were not used in this outcome measure due to limited data set. Skindex is a dermatology survey whose scores are normalized to a 0-100 scale with higher scores indicating worse quality of life. We report here the change in overall Skindex score after 12 cycles of treatment (Score at 12 cycles - Score at Baseline).

Outcome measures

Outcome measures
Measure	Treatment (Selumetinib) n=5 Participants Participants receive selumetinib capsules at a dose of 50mg by mouth (PO) twice daily (BID) every 12 hours with option to increase to 75mg PO BID after first cycle if tolerated. Treatment repeats every 28 days (1 cycle = 28 days) for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Participants who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles. Volume decrease defined as a greater than or equal to 20 percent decrease in the sum of the volumes of the smaller and/or larger target cutaneous neurofibromas.
Changes in Skin Related Morbidity	-1.72 score on a scale Interval -15.52 to 12.07

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 1 year

Population: Trial was terminated due to low accrual that was exacerbated by the COVID-19 pandemic leading to limited data set for this outcome measure. Not enough samples to justify proceeding with this analysis.

Will be tested for statistical significance using a Wilcoxon signed rank test.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 1 year

Will be correlated with tumor volume changes using Spearman rank correlation. Exploratory comparisons between patients with a tumor response and those without a response will be done using a Wilcoxon rank sum test.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Selumetinib)

Serious events: 5 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Selumetinib) n=11 participants at risk Participants receive selumetinib capsules at a dose of 50mg by mouth (PO) twice daily (BID) every 12 hours with option to increase to 75mg PO BID after first cycle. Treatment repeats every 28 days (1 cycle = 28 days) for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Participants who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles. Volume decrease defined as a greater than or equal to 20 percent decrease in the sum of the volumes of the smaller and/or larger target cutaneous neurofibromas.
Eye disorders Eye disorders - Other, specify	9.1% 1/11 • Number of events 1 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Immune system disorders Immune system disorders - Other, specify	9.1% 1/11 • Number of events 1 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	9.1% 1/11 • Number of events 1 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor hemorrhage	9.1% 1/11 • Number of events 5 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Vascular disorders Hypertension	9.1% 1/11 • Number of events 2 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)

Other adverse events

Other adverse events
Measure	Treatment (Selumetinib) n=11 participants at risk Participants receive selumetinib capsules at a dose of 50mg by mouth (PO) twice daily (BID) every 12 hours with option to increase to 75mg PO BID after first cycle. Treatment repeats every 28 days (1 cycle = 28 days) for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Participants who experience a volume decrease in the target cutaneous neurofibromas may continue treatment for 12 additional cycles. Volume decrease defined as a greater than or equal to 20 percent decrease in the sum of the volumes of the smaller and/or larger target cutaneous neurofibromas.
Blood and lymphatic system disorders Eosinophilia	9.1% 1/11 • Number of events 1 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Gastrointestinal disorders Constipation	9.1% 1/11 • Number of events 2 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Gastrointestinal disorders Diarrhea	36.4% 4/11 • Number of events 32 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Gastrointestinal disorders Dry mouth	9.1% 1/11 • Number of events 15 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Gastrointestinal disorders Gastrointestinal disorders - Other, specify (Dark stools)	9.1% 1/11 • Number of events 2 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Gastrointestinal disorders Nausea	9.1% 1/11 • Number of events 17 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Gastrointestinal disorders Vomiting	9.1% 1/11 • Number of events 2 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
General disorders Edema face	9.1% 1/11 • Number of events 2 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
General disorders Edema limbs	27.3% 3/11 • Number of events 7 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
General disorders Fatigue	9.1% 1/11 • Number of events 2 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
General disorders Flu like symptoms	9.1% 1/11 • Number of events 1 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Infections and infestations Alanine aminotransferase increased	18.2% 2/11 • Number of events 7 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Infections and infestations Aspartate aminotransferase increased	9.1% 1/11 • Number of events 10 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Infections and infestations Paronychia	9.1% 1/11 • Number of events 13 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Investigations Alanine aminotransferase increased	9.1% 1/11 • Number of events 17 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Investigations Alkaline phosphatase increased	9.1% 1/11 • Number of events 10 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Investigations CPK increased	9.1% 1/11 • Number of events 5 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Investigations Lipase increased	18.2% 2/11 • Number of events 13 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Investigations Serum amylase increased	9.1% 1/11 • Number of events 2 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Nervous system disorders Dizziness	9.1% 1/11 • Number of events 2 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Nervous system disorders Dysgeusia	9.1% 1/11 • Number of events 15 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Reproductive system and breast disorders Vaginal dryness	9.1% 1/11 • Number of events 2 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Respiratory, thoracic and mediastinal disorders Dyspnea	9.1% 1/11 • Number of events 2 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Skin and subcutaneous tissue disorders Alopecia	9.1% 1/11 • Number of events 6 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Skin and subcutaneous tissue disorders Dry skin	9.1% 1/11 • Number of events 15 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Skin and subcutaneous tissue disorders Nail loss	9.1% 1/11 • Number of events 3 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Skin and subcutaneous tissue disorders Pruritus	9.1% 1/11 • Number of events 5 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Skin and subcutaneous tissue disorders Rash acneiform	54.5% 6/11 • Number of events 41 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify (Onchomycosis)	18.2% 2/11 • Number of events 25 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify (Skin fissures)	9.1% 1/11 • Number of events 3 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)
Vascular disorders Hypertension	18.2% 2/11 • Number of events 16 • Baseline through study completion, a maximum of 36 cycles (approximately 3 years)

Additional Information

Bruce R. Korf, MD, PhD

UAB Heersink School of Medicine

Phone: 205-996-9487

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60