Trial Outcomes & Findings for An Open-Label Phase II Study of the Combination of GSK2118436 and GSK1120212 in Patients With Metastatic Melanoma Which is Refractory or Resistant to BRAF Inhibitor (NCT NCT01619774)

NCT ID: NCT01619774

Last Updated: 2016-12-12

Results Overview

Overall response rate defined as percentage of subjects with a confirmed complete response (CR) or a partial response (PR) at any time as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Clinical responses will be evaluated using RECIST 1.1 criteria after every 2 cycles (8 weeks). Complete Response (CR): Disappearance all lesions; pathological lymph nodes reduction in short axis to \<10 mm. Partial Response (PR): \>30% decrease in sum diameters of lesions, reference baseline sum diameters. Progressive Disease (PD): \>20% increase in sum diameters of lesions, reference smallest sum on study (includes baseline sum if smallest on study); relative increase of 20%, sum must also demonstrate absolute increase of \>5 mm; appearance of 1 or \> new lesions considered progression). Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD, reference smallest sum diameters while on study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Evaluation every 8 weeks (2 cycles) up to 12 months

Results posted on

2016-12-12

Participant Flow

Recruitment Period: September 28, 2012 to October 23, 2014. All recruitment done at The University of Texas MD Anderson Cancer Center.

Of the 28 participants screened, five (5) were not eligible following enrollment thus were excluded prior to treatment assignment.

Participant milestones

Participant milestones
Measure	GSK2118436 + GSK1120212 GSK1120212 2 mg by mouth once a day, and GSK2118436 150 mg by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart).
Overall Study STARTED	23
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Open-Label Phase II Study of the Combination of GSK2118436 and GSK1120212 in Patients With Metastatic Melanoma Which is Refractory or Resistant to BRAF Inhibitor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK2118436 + GSK1120212 n=23 Participants GSK1120212 2 mg by mouth once a day, and GSK2118436 150 mg by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart).
Age, Continuous	54 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants

PRIMARY outcome

Timeframe: Evaluation every 8 weeks (2 cycles) up to 12 months

Population: Three of the 23 participants were not evaluable for response.

Outcome measures

Outcome measures
Measure	GSK2118436 + GSK1120212 n=20 Participants GSK1120212 2 mg by mouth once a day, and GSK2118436 150 mg by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart).
Overall Response Rate (ORR)	10 Percentage of Participants

PRIMARY outcome

Timeframe: Evaluation every 8 weeks (2 cycles) up to 12 months

Clinical responses evaluated using RECIST 1.1 criteria after every 2 cycles (8 weeks). Complete Response (CR): Disappearance all lesions; pathological lymph nodes reduction in short axis to \<10 mm. Partial Response (PR): \>30% decrease in sum diameters of lesions, reference baseline sum diameters. Progressive Disease (PD): \>20% increase in sum diameters of lesions, reference smallest sum on study (includes baseline sum if smallest on study); relative increase of 20%, sum must also demonstrate absolute increase of \>5 mm; appearance of 1 or \> new lesions considered progression). Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD, reference smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	GSK2118436 + GSK1120212 n=23 Participants GSK1120212 2 mg by mouth once a day, and GSK2118436 150 mg by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart).
Number of Participants by Response Complete Response (CR)	0 participants
Number of Participants by Response Partial Response (PR)	2 participants
Number of Participants by Response Progressive Disease (PD)	7 participants
Number of Participants by Response Stable Disease (SD)	11 participants
Number of Participants by Response Not Evaluable	3 participants

SECONDARY outcome

Timeframe: Evaluation every 8 weeks (2 cycles) up to 12 months

Population: Three of the 23 participants were not evaluable for response therefore not included PFS analysis.

Duration of response defined for subjects with a confirmed complete response (CR) or partial response (PR), as time from the first documented evidence of a CR or PR until the first documented disease progression or death due to any cause. Progression free survival (PFS) estimated and summarized using the method of Kaplan and Meier.

Outcome measures

Outcome measures
Measure	GSK2118436 + GSK1120212 n=20 Participants GSK1120212 2 mg by mouth once a day, and GSK2118436 150 mg by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart).
Progression-Free Survival (PFS)	13 weeks Interval 8.0 to 16.0

Adverse Events

GSK2118436 + GSK1120212

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GSK2118436 + GSK1120212 n=23 participants at risk GSK1120212 2 mg by mouth once a day, and GSK2118436 150 mg by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart).
Musculoskeletal and connective tissue disorders Arthralgias	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Infections and infestations Decreased ejection fraction	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Cardiac disorders Sinus Tachycardia	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Vascular disorders Thromboembolic Event	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.

Other adverse events

Other adverse events
Measure	GSK2118436 + GSK1120212 n=23 participants at risk GSK1120212 2 mg by mouth once a day, and GSK2118436 150 mg by mouth 2 times every day (1 time in the morning and 1 time in the evening, about 12 hours apart).
Investigations Alkaline phosphatase increased	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Immune system disorders Allergic reaction	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Psychiatric disorders Anxiety	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Investigations Aspartate aminotransferase increased	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Investigations Blood bilirubin increased	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Congenital, familial and genetic disorders Congenital defect	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Investigations Creatinine increased	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Metabolism and nutrition disorders Dehydration	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Gastrointestinal disorders Dyspepsia	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
General disorders Edema face	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
General disorders Flu like symptoms	4.3% 1/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Ear and labyrinth disorders Hearing impaired	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Metabolism and nutrition disorders Hypomagnesemia	4.3% 1/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Cardiac disorders Left ventricular systolic dysfunction	4.3% 1/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Respiratory, thoracic and mediastinal disorders Lung infection	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Infections and infestations Sepsis	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Respiratory, thoracic and mediastinal disorders Sinus disorder	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Infections and infestations Sinusitis	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Skin and subcutaneous tissue disorders Skin infection	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Cardiac disorders Supraventricular tachycardia	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Investigations White blood cell decreased	4.3% 1/23 • Number of events 1 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Blood and lymphatic system disorders Anemia	8.7% 2/23 • Number of events 4 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Psychiatric disorders Confusion	8.7% 2/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Respiratory, thoracic and mediastinal disorders Cough	8.7% 2/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
General disorders Edema limbs	8.7% 2/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Investigations Investigations - Other Thromobembolic	8.7% 2/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.7% 2/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Skin and subcutaneous tissue disorders Rash maculo-papular	8.7% 2/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	8.7% 2/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Social circumstances Social circumstances - mental health issue	8.7% 2/23 • Number of events 2 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Investigations Weight loss	8.7% 2/23 • Number of events 3 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Gastrointestinal disorders Mucositis oral	13.0% 3/23 • Number of events 4 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Musculoskeletal and connective tissue disorders Joint effusion	17.4% 4/23 • Number of events 5 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Gastrointestinal disorders Diarrhea	21.7% 5/23 • Number of events 7 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Nervous system disorders Dizziness	21.7% 5/23 • Number of events 7 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Infections and infestations Infection	26.1% 6/23 • Number of events 6 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
General disorders Chills	30.4% 7/23 • Number of events 10 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
General disorders Pain in extremity	30.4% 7/23 • Number of events 15 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Nervous system disorders Peripheral sensory neuropathy	30.4% 7/23 • Number of events 7 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Eye disorders Blurred vision	30.4% 7/23 • Number of events 7 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Reproductive system and breast disorders Hot flashes	34.8% 8/23 • Number of events 9 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Musculoskeletal and connective tissue disorders Arthritis	34.8% 8/23 • Number of events 9 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Skin and subcutaneous tissue disorders Pruritus	34.8% 8/23 • Number of events 9 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Gastrointestinal disorders Vomiting	39.1% 9/23 • Number of events 15 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Metabolism and nutrition disorders Anorexia	43.5% 10/23 • Number of events 10 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnea	39.1% 9/23 • Number of events 10 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Nervous system disorders Headache	39.1% 9/23 • Number of events 15 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	52.2% 12/23 • Number of events 13 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Skin and subcutaneous tissue disorders Rash acneiform	47.8% 11/23 • Number of events 12 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Gastrointestinal disorders Constipation	56.5% 13/23 • Number of events 15 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
General disorders Pain	56.5% 13/23 • Number of events 17 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Investigations Fever	60.9% 14/23 • Number of events 26 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Vascular disorders Hypertension	60.9% 14/23 • Number of events 21 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Gastrointestinal disorders Dry mouth	65.2% 15/23 • Number of events 17 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Skin and subcutaneous tissue disorders Dry skin	65.2% 15/23 • Number of events 16 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
Gastrointestinal disorders Nausea	69.6% 16/23 • Number of events 25 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.
General disorders Fatigue	82.6% 19/23 • Number of events 37 • Adverse Event collection from the time of the first protocol-specific intervention, through each 4 week cycle until 30 days after the last dose of drug up to 12 weeks.

Additional Information

Michael Davies, Associate Professor, Melanoma Medical Oncology

University of Texas (UT) MD Anderson Cancer Center

Phone: 713-792-7734

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place