Trial Outcomes & Findings for The Effects of Treatment With Vemurafenib on the Immune System in Advanced Melanoma (NCT NCT01942993)

NCT ID: NCT01942993

Last Updated: 2020-09-30

Results Overview

Immuno-fluorescence and flow cytometry will be performed on blood specimens obtained to determine changes in the immune cell signature in the blood on day 8 and day 57 after initiation of vemurafenib treatment as compared to baseline

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

baseline, day 8, and day 57

Results posted on

2020-09-30

Participant Flow

Participant milestones

Participant milestones
Measure	Vemurafenib 960 mg (four tablets of 240 mg each) of vemurafenib PO BID Vemurafenib: Vemurafenib will be administered at the FDA approved dose of 960 mg approximately 12 hours apart with or without a meal. Vemurafenib is provided at 240-mg film-coated tablets packed in bottles for oral administration. Vemurafenib should be swallowed whole with a glass of water and the medication should not be chewed or crushed. Management of symptomatic adverse events may require dose reductions, treatment interruptions, or treatment discontinuation. Dose reductions below 480 mg twice daily are not recommended.
Overall Study STARTED	3
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Vemurafenib 960 mg (four tablets of 240 mg each) of vemurafenib PO BID Vemurafenib: Vemurafenib will be administered at the FDA approved dose of 960 mg approximately 12 hours apart with or without a meal. Vemurafenib is provided at 240-mg film-coated tablets packed in bottles for oral administration. Vemurafenib should be swallowed whole with a glass of water and the medication should not be chewed or crushed. Management of symptomatic adverse events may require dose reductions, treatment interruptions, or treatment discontinuation. Dose reductions below 480 mg twice daily are not recommended.
Overall Study Lost to Follow-up	1
Overall Study Physician Decision	1

Baseline Characteristics

The Effects of Treatment With Vemurafenib on the Immune System in Advanced Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vemurafenib n=3 Participants 960 mg (four tablets of 240 mg each) of vemurafenib PO BID Vemurafenib: Vemurafenib will be administered at the FDA approved dose of 960 mg approximately 12 hours apart with or without a meal. Vemurafenib is provided at 240-mg film-coated tablets packed in bottles for oral administration. Vemurafenib should be swallowed whole with a glass of water and the medication should not be chewed or crushed. Management of symptomatic adverse events may require dose reductions, treatment interruptions, or treatment discontinuation. Dose reductions below 480 mg twice daily are not recommended.
Age, Continuous	63 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, day 8, and day 57

Population: Data not collected

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline, day 8-10, and day 57

Population: data not collected, no patients had research tumor biopsies

Immuno-fluorescence and flow cytometry will be performed on tumor specimens obtained to determine changes in the immune cell signature in the tumor on day 8-10 and day 57 after initiation of vemurafenib treatment as compared to baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline, day 8, and day 57

Population: Data not collected

Global changes in the blood transcriptome in response to vemurafenib therapy will be performed using gene expression arrays. Change in the blood transcriptosome on day 8 and day 57 as compared to baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and day 8-10

Population: Data not collected. No patients had research tumor biopsies.

Global changes in the transcriptosome of tumor associated immune cells in response to therapy will be performed using gene expression arrays. The transcriptosome in tumor will be compared on purified tumor immune cells obtained from a pretreatment tumor biopsy performed at baseline and a second biopsy obtained after starting treatment and obtained between days 8-10.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline day 8, and day 57

Population: Data not collected

change in dendritic cell function at day 8 and day 57 as compared to baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and day 8-10

Population: Data not collected. No patients had research tumor biopsies.

Changes in dendritic cell function in tumor on day 8-10 as compared to baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline, day 8, and day 57

Population: Data not collected

Changes in macrophage function in blood at day 8 and day 57 as compared to baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and day 8-10

Population: Data not collected. No patients had research tumor biopsies.

changes in macrophage function in tumor on day 8-10 as compared to baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline, day 8, and day 57

Population: Data not collected.

changes in global T cell function in blood on day 8 and day 57 as compared to baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and day 8-10

Population: Data not collected. No patients had research tumor biopsies.

Changes in Global T cell function in Tumor on day 8 as compared to baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline, day 8, day 15 and day 126

Population: Data not collected.

Changes in Tumor Antigen Specific T cell Function using CD154 induction assay on day 8, day 15 and day 126 as compared to baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and day 8-10

Population: Data not collected. No patients had research tumor biopsies.

Changes in Histocytometry of tumor on day 8-10 as compared to baseline. Histocytometry is a novel microscopic analytical method (Gerner et al. 2012) which combines the advantages of flow cytometry and Microscopic techniques. This techniques allows for the visualization and quantification of phenotypically complex cellular subsets and provides spatial and cell-cell interactions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 57 days

Response to vemurafenib treatment based on changes in tumor burden using CT or MRI imaging studies. Response are categorized as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD),

Outcome measures

Outcome measures
Measure	Vemurafenib n=3 Participants 960 mg (four tablets of 240 mg each) of vemurafenib PO BID Vemurafenib: Vemurafenib will be administered at the FDA approved dose of 960 mg approximately 12 hours apart with or without a meal. Vemurafenib is provided at 240-mg film-coated tablets packed in bottles for oral administration. Vemurafenib should be swallowed whole with a glass of water and the medication should not be chewed or crushed. Management of symptomatic adverse events may require dose reductions, treatment interruptions, or treatment discontinuation. Dose reductions below 480 mg twice daily are not recommended.
Response to Vemurafenib Treatment CR	0 Participants
Response to Vemurafenib Treatment PR	1 Participants
Response to Vemurafenib Treatment PD	0 Participants
Response to Vemurafenib Treatment SD	2 Participants

SECONDARY outcome

Timeframe: up to 5 months

Number of participants who developed cutaneous squamous cell carcinomas while on the study

Outcome measures

Outcome measures
Measure	Vemurafenib n=3 Participants 960 mg (four tablets of 240 mg each) of vemurafenib PO BID Vemurafenib: Vemurafenib will be administered at the FDA approved dose of 960 mg approximately 12 hours apart with or without a meal. Vemurafenib is provided at 240-mg film-coated tablets packed in bottles for oral administration. Vemurafenib should be swallowed whole with a glass of water and the medication should not be chewed or crushed. Management of symptomatic adverse events may require dose reductions, treatment interruptions, or treatment discontinuation. Dose reductions below 480 mg twice daily are not recommended.
Number of Participants Who Developed of Cutaneous Squamous Cell Carcinomas	0 Participants

Adverse Events

Vemurafenib

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Vemurafenib n=3 participants at risk 960 mg (four tablets of 240 mg each) of vemurafenib PO BID Vemurafenib: Vemurafenib will be administered at the FDA approved dose of 960 mg approximately 12 hours apart with or without a meal. Vemurafenib is provided at 240-mg film-coated tablets packed in bottles for oral administration. Vemurafenib should be swallowed whole with a glass of water and the medication should not be chewed or crushed. Management of symptomatic adverse events may require dose reductions, treatment interruptions, or treatment discontinuation. Dose reductions below 480 mg twice daily are not recommended.
Ear and labyrinth disorders Tinnitus	33.3% 1/3 • 5 months
General disorders Pain	100.0% 3/3 • 5 months
Metabolism and nutrition disorders Weight Loss	33.3% 1/3 • 5 months
Cardiac disorders Hypotension	33.3% 1/3 • 5 months
General disorders Fatigue	100.0% 3/3 • 5 months
Blood and lymphatic system disorders Anemia	66.7% 2/3 • 5 months
Metabolism and nutrition disorders Hypoalbuminemia	33.3% 1/3 • 5 months
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • 5 months
Psychiatric disorders Insomnia	66.7% 2/3 • 5 months
Metabolism and nutrition disorders Hypocalcemia	33.3% 1/3 • 5 months
General disorders Chills	33.3% 1/3 • 5 months
Investigations Alkaline Phosphatase Increased	33.3% 1/3 • 5 months
Metabolism and nutrition disorders Hyperkalemia	66.7% 2/3 • 5 months
Injury, poisoning and procedural complications Fall	33.3% 1/3 • 5 months
Skin and subcutaneous tissue disorders Rash	66.7% 2/3 • 5 months
General disorders Fever	33.3% 1/3 • 5 months
Musculoskeletal and connective tissue disorders Arthralgias	66.7% 2/3 • 5 months
Nervous system disorders Headache	33.3% 1/3 • 5 months
Eye disorders Anterior Uveitis	33.3% 1/3 • 5 months
Metabolism and nutrition disorders Hypernatremia	33.3% 1/3 • 5 months
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • 5 months
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • 5 months
Blood and lymphatic system disorders White Blood Cell Decreased	33.3% 1/3 • 5 months
Investigations Electrocardiogram QT corrected Interval Prolongation	33.3% 1/3 • 5 months
Endocrine disorders Hypoglycemia	33.3% 1/3 • 5 months

Additional Information

Dr. Philip A Friedlander

Icahn School of Medicine at Mount Sinai

Phone: 212-824-8584

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place