A Study of RO5185426 in Patients With Metastatic Melanoma

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01248936
• Collaborator: (none)
• Enrollment: 374
• Locations: 28
• Arm: 1
• Duration (Months): 10
• Patients Per Site: 13.4
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This is an open-label, non-comparative, multicenter, expanded access study of RO5185426 in patients who have received prior systemic therapy for metastatic melanoma and who have no other satisfactory treatment options.

Condition or Disease	Intervention/Treatment	Phase
Malignant Melanoma	Drug: RO5185426	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 374 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A SINGLE ARM, OPEN LABEL, EXPANDED ACCESS STUDY OF RG7204 IN PREVIOUSLY TREATED PATIENTS WITH METASTATIC MELANOMA
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Overall Trial Participants received vemurafenib 960 milligram (mg) orally two times a day for up to one year. Participants were treated until disease progression, unmanageable toxicity most probably attributable to vemurafenib, withdrawal of consent, and study termination by the sponsor	Drug: RO5185426

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Adverse Event, Adverse Events With Severity, Adverse Events Leading to Discontinuation [Up to 1 year]

   An Adverse Event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs will be graded according to the 'National Cancer Institute Common Terminology Criteria for Adverse Events' (NCI CTCAE, v4.0). However Laboratory data will be summarized by grade using the NCI CTCAE, v4.0 toxicity grade.

2. Number of Participants With Any Serious Adverse Event, Death and Cause of Death [Up to 1 year]

   Serious Adverse Event (SAEs) is defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; resulted in disability; or was a congenital anomaly. Number of participants who died and the cause of death are also recorded.

Secondary Outcome Measures

1. Number of Participants With Best Overall Response (Unconfirmed) [Up to 1 year]

   The best overall response (unconfirmed) is the best response recorded from the start of the treatment until disease progression/recurrence which was unconfirmed. Participants were assessed for best overall response by investigator as per 'Response Evaluation Criteria in Solid Tumors' (RECIST v1.1).

2. Number of Participants With Best Overall Response (Unconfirmed) by ECOG Performance [Up to 1 year]

   The best overall response recorded from the start of the treatment until disease progression/recurrence which was unconfirmed in patients with Eastern Cooperative Oncology Group (ECOG) performance status 2 or 3/0 or 1. Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. This endpoint was tumor response category according to investigator assessment per RECIST v1.1 for efficacy assessment. The 'n' is number of participants with ECOG performance status in each criteria.

3. Number of Participants With Best Overall Response (Confirmed) [Up to 1 year]

   The best overall response (confirmed) is the best response recorded from the start of the treatment until disease progression/recurrence which was confirmed. Participants were assessed for best overall response by investigator as per RECIST v1.1.

4. Number of Participants With Best Overall Response (Confirmed) by ECOG Performance [Up to 1 year]

   The best overall response recorded from the start of the treatment until disease progression/recurrence which was confirmed in patients with Eastern Cooperative Oncology Group (ECOG) performance status 2 or 3/0 or 1. Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants were assessed for best overall response by investigator as per RECIST v1.1. The 'n' is number of participants with ECOG performance status in each criteria.

5. Mean Time to Complete Response/Partial Response [Up to 1 year]

   Mean time to Complete Response (CR)/Partial Response(PR) (confirmed or unconfirmed was assessed). Participants were assessed for best overall response by investigator as per RECIST v1.1.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed metastatic melanoma with documented BRAF V600E mutation, determined by the cobas BRAF V600 mutation test

• Patients with either measurable or non-measurable disease

• Adequate recovery from most recent systemic or local treatment for metastatic melanoma

• Adequate organ function

• For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of RO5185426

• For men with female partners of childbearing potential, agreement to use a latex condom, and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of RO5185426

• Negative serum or urine pregnancy test within 7 days of commencement of treatment in premenopausal women. Women who are either surgically sterile or have been post-menopausal for at least 1 year are eligible to participate in this study

• Agreement not to donate blood or blood products during the study and for at least 6 months after discontinuation of RO5185426; for male patients, agreement not to donate sperm during the study and for at least 6 months after discontinuation of RO5185426

Exclusion Criteria:

• Pregnant or breast-feeding

• Concurrent anti-tumor therapy

• Uncontrolled medical illness

• History of congenital prolonged QT syndrome or patients with a mean QTc interval greater than 470 milliseconds at baseline, or ongoing grade 2 or greater cardiac arrhythmia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tucson	Arizona	United States	85724-5078
2		Los Angeles	California	United States	90095
3		San Francisco	California	United States	94115
4		San Francisco	California	United States	94117
5		Santa Monica	California	United States	90025
6		Aurora	Colorado	United States	80045
7		New Haven	Connecticut	United States	06520-8063
8		Palm Harbor	Florida	United States	34684
9		Tampa	Florida	United States	33612-9497
10		Atlanta	Georgia	United States	30322
11		Park Ridge	Illinois	United States	60068
12		Boston	Massachusetts	United States	02114
13		Boston	Massachusetts	United States	02215
14		Detroit	Michigan	United States	48201
15		St. Louis	Missouri	United States	63110
16		New York	New York	United States	10016
17		New York	New York	United States	10029
18		New York	New York	United States	10032
19		New York	New York	United States	10065
20		Cincinnati	Ohio	United States	45242
21		Oklahoma City	Oklahoma	United States	73104
22		Portland	Oregon	United States	97225
23		Philadelphia	Pennsylvania	United States	19104
24		Columbia	South Carolina	United States	29210
25		Nashville	Tennessee	United States	37203
26		Dallas	Texas	United States	75246
27		Richmond	Virginia	United States	23230
28		Seattle	Washington	United States	98195

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01248936
• Other Study ID Numbers: ML25597
• First Posted: Nov 25, 2010
• Last Update Posted: Aug 12, 2016
• Last Verified: Jul 1, 2016

• Additional relevant MeSH terms: Melanoma

Study Results

Participant Flow

Recruitment Details	The study was conducted in 29 study sites in the United States (US). The study period was from 10 December 2010 to 24 October 2011.
Pre-assignment Detail	Overall, 745 participants were screened during the study, of which 374 were enrolled to receive study treatment; the main reason for screen failure was negative cobas test, consent withdrawal, BRAF test not performed, patient died or progressed, and other unspecified reasons. Of 374 participants, 3 did not receive treatment after enrollment.

Arm/Group Title	Overall Trial
Arm/Group Description	Participants received vemurafenib 960 milligram (mg) orally two times a day for up to one year. Participants were treated until disease progression, unmanageable toxicity most probably attributable to vemurafenib, withdrawal of consent, and study termination by the sponsor.
Period Title: Overall Study
STARTED	374
COMPLETED	0
NOT COMPLETED	374

Baseline Characteristics

Arm/Group Title	Overall Trial
Arm/Group Description	Participants received vemurafenib 960 mg orally two times a day for up to one year. Participants were treated until disease progression, unmanageable toxicity most probably attributable to vemurafenib, withdrawal of consent, and study termination by the sponsor.
Overall Participants	371
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.5 (13.8)
Age, Customized (participants) [Number]
Adolescents (12-17 year)	1 0.3%
From 18 - 64 years	289 77.9%
From 65 - 84 years	79 21.3%
Over 85 years	2 0.5%
Sex: Female, Male (Count of Participants)
Female	142 38.3%
Male	229 61.7%

Outcome Measures

1. Secondary Outcome

Title	Number of Participants With Best Overall Response (Unconfirmed)
Description	The best overall response (unconfirmed) is the best response recorded from the start of the treatment until disease progression/recurrence which was unconfirmed. Participants were assessed for best overall response by investigator as per 'Response Evaluation Criteria in Solid Tumors' (RECIST v1.1).
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

The efficacy population was defined as treated participants who had measurable disease at baseline and at least one post-baseline tumor assessment.

Arm/Group Title	Overall Trial
Arm/Group Description	Participants received vemurafenib 960 mg orally two times a day for up to one year. Participants were treated until disease progression, unmanageable toxicity most probably attributable to vemurafenib, withdrawal of consent, and study termination by the sponsor
Measure Participants	241
Number [participants]	129 34.8%

2. Secondary Outcome

Title	Number of Participants With Best Overall Response (Unconfirmed) by ECOG Performance
Description	The best overall response recorded from the start of the treatment until disease progression/recurrence which was unconfirmed in patients with Eastern Cooperative Oncology Group (ECOG) performance status 2 or 3/0 or 1. Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. This endpoint was tumor response category according to investigator assessment per RECIST v1.1 for efficacy assessment. The 'n' is number of participants with ECOG performance status in each criteria.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

The efficacy population was defined as treated patients who had measurable disease at baseline and at least one post-baseline tumor assessment.

Arm/Group Title	Overall Trial
Arm/Group Description	Participants received vemurafenib 960 mg orally two times a day for up to one year. Participants were treated until disease progression, unmanageable toxicity most probably attributable to vemurafenib, withdrawal of consent, and study termination by the sponsor
Measure Participants	241
ECOG performance status 2 or 3; n=31	13 3.5%
ECOG performance status 0 or 1; n=210	116 31.3%

3. Secondary Outcome

Title	Number of Participants With Best Overall Response (Confirmed)
Description	The best overall response (confirmed) is the best response recorded from the start of the treatment until disease progression/recurrence which was confirmed. Participants were assessed for best overall response by investigator as per RECIST v1.1.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

The efficacy population was defined as treated participants who had measurable disease at baseline and at least one post-baseline tumor assessment.

Arm/Group Title	Overall Trial
Arm/Group Description	Participants received vemurafenib 960 mg orally two times a day for up to one year. Participants were treated until disease progression, unmanageable toxicity most probably attributable to vemurafenib, withdrawal of consent, and study termination by the sponsor
Measure Participants	241
Number [Participants]	26 7%

4. Secondary Outcome

Title	Number of Participants With Best Overall Response (Confirmed) by ECOG Performance
Description	The best overall response recorded from the start of the treatment until disease progression/recurrence which was confirmed in patients with Eastern Cooperative Oncology Group (ECOG) performance status 2 or 3/0 or 1. Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants were assessed for best overall response by investigator as per RECIST v1.1. The 'n' is number of participants with ECOG performance status in each criteria.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

The efficacy population was defined as treated participants who had measurable disease at baseline and at least one post-baseline tumor assessment.

Arm/Group Title	Overall Trial
Arm/Group Description	Participants received vemurafenib 960 mg orally two times a day for up to one year. Participants were treated until disease progression, unmanageable toxicity most probably attributable to vemurafenib, withdrawal of consent, and study termination by the sponsor
Measure Participants	241
ECOG performance status 2 or 3); n= 31	1 0.3%
ECOG performance status 0 or 1); n= 210	25 6.7%

5. Secondary Outcome

Title	Mean Time to Complete Response/Partial Response
Description	Mean time to Complete Response (CR)/Partial Response(PR) (confirmed or unconfirmed was assessed). Participants were assessed for best overall response by investigator as per RECIST v1.1.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

The efficacy population was defined as treated participants who had measurable disease at baseline and at least one post-baseline tumor assessment.

Arm/Group Title	Overall Trial
Arm/Group Description	Participants received Vemurafenib 960 mg orally two times a day for up to one year. Participants were treated until disease progression, Unmanageable toxicity most probably attributable to Vemurafenib, withdrawal of consent, and Study termination by the Sponsor
Measure Participants	241
Mean time to confirmed CR or PR	1.8 (0.3)
Mean time to unconfirmed CR or PR	2.0 (0.7)

6. Primary Outcome

Title	Number of Participants With Any Adverse Event, Adverse Events With Severity, Adverse Events Leading to Discontinuation
Description	An Adverse Event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs will be graded according to the 'National Cancer Institute Common Terminology Criteria for Adverse Events' (NCI CTCAE, v4.0). However Laboratory data will be summarized by grade using the NCI CTCAE, v4.0 toxicity grade.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

The safety population was defined as participants who received at least one dose, or a partial dose, of vemurafenib.

Arm/Group Title	Overall Trial
Arm/Group Description	Participants received vemurafenib 960 mg orally two times a day for up to one year. Participants were treated until disease progression, unmanageable toxicity most probably attributable to vemurafenib, withdrawal of consent, and study termination by the sponsor
Measure Participants	371
Any AE	346 93.3%
Grade 3 AEs	115 31%
Grade 4 AEs	15 4%
Grade 5 AEs	7 1.9%
AEs leading to discontinuation	9 2.4%

7. Primary Outcome

Title	Number of Participants With Any Serious Adverse Event, Death and Cause of Death
Description	Serious Adverse Event (SAEs) is defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; resulted in disability; or was a congenital anomaly. Number of participants who died and the cause of death are also recorded.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

The safety population was defined as participants who received at least one dose, or a partial dose, of vemurafenib.

Arm/Group Title	Overall Trial
Arm/Group Description	Participants received vemurafenib 960 mg orally two times a day for up to one year. Participants were treated until disease progression, unmanageable toxicity most probably attributable to vemurafenib, withdrawal of consent, and study termination by the sponsor
Measure Participants	371
Any SAEs	83 22.4%
All Deaths	43 11.6%
Death due to progression of disease	22 5.9%
Death due to adverse event	8 2.2%
Deaths which are not related to study drug	6 1.6%
Deaths which are related to study drug	2 0.5%

Adverse Events

Time Frame	Up to 1 Year
Adverse Event Reporting Description	Serious adverse events and non-serious adverse events are reported in safety analysis set, which consists of all participants who received at least one dose of study medication and had a safety assessment performed post baseline.
Arm/Group Title	Overall Trial
Arm/Group Description	Participants received vemurafenib 960 mg orally two times a day for up to one year. Participants were treated until disease progression, unmanageable toxicity most probably attributable to vemurafenib, withdrawal of consent, and study termination by the sponsor
All Cause Mortality
	Overall Trial
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Overall Trial
	Affected / at Risk (%)	# Events
Total	83/371 (22.4%)
Blood and lymphatic system disorders
Anaemia	3/371 (0.8%)
Lymphopenia	1/371 (0.3%)
Neutropenia	1/371 (0.3%)
Cardiac disorders
Atrial Flutter	1/371 (0.3%)
Cardiac failure congestive	1/371 (0.3%)
Pericardial Effusion	1/371 (0.3%)
Eye disorders
Pupils unequal	1/371 (0.3%)
Uveitis	1/371 (0.3%)
Gastrointestinal disorders
Vomiting	5/371 (1.3%)
Abdominal Pain	3/371 (0.8%)
Nausea	2/371 (0.5%)
Ascites	1/371 (0.3%)
Constipation	1/371 (0.3%)
Diverticular Perforation	1/371 (0.3%)
Gastric Ulcer	1/371 (0.3%)
Gastrointestinal Haemorrhage	1/371 (0.3%)
Small Intestinal Obstruction	1/371 (0.3%)
General disorders
Pyrexia	5/371 (1.3%)
Death	2/371 (0.5%)
Asthenia	1/371 (0.3%)
Chest Pain	1/371 (0.3%)
Drug Withdrawal Syndrome	1/371 (0.3%)
Fatigue	1/371 (0.3%)
Multi-organ failure	1/371 (0.3%)
Pain	1/371 (0.3%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/371 (0.3%)
Infections and infestations
Cellulitis	4/371 (1.1%)
Urinary Tract Infection	4/371 (1.1%)
Pneumonia	3/371 (0.8%)
Bacterial Infection	1/371 (0.3%)
Clostridial infection	1/371 (0.3%)
Sepsis	1/371 (0.3%)
Injury, poisoning and procedural complications
Procedural pain	1/371 (0.3%)
Spinal compression fracture	1/371 (0.3%)
Toxicity to various agents	1/371 (0.3%)
Investigations
Electrocardiogram Qt Prolonged	3/371 (0.8%)
Blood Bilirubin Increased	1/371 (0.3%)
Blood Creatine Phosphokinase Increased	1/371 (0.3%)
Blood Uric Acid Increased	1/371 (0.3%)
Neutrophil count decreased	1/371 (0.3%)
Metabolism and nutrition disorders
Dehydration	5/371 (1.3%)
Hyperkalaemia	2/371 (0.5%)
Failure To Thrive	1/371 (0.3%)
Hypokalaemia	1/371 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/371 (0.5%)
Neck Pain	2/371 (0.5%)
Back Pain	1/371 (0.3%)
Musculoskeletal Pain	1/371 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases To Central Nervous System	1/371 (0.3%)
Nervous system disorders
Convulsion	5/371 (1.3%)
Headache	2/371 (0.5%)
Cerebral haemorrhage	1/371 (0.3%)
Hydrocephalus	1/371 (0.3%)
Lethargy	1/371 (0.3%)
Lumbar Radiculopathy	1/371 (0.3%)
Paraesthesia	1/371 (0.3%)
Spinal Cord Compression	1/371 (0.3%)
Psychiatric disorders
Confusional State	3/371 (0.8%)
Mental Status Changes	2/371 (0.5%)
Paranoia	1/371 (0.3%)
Renal and urinary disorders
Renal Colic	1/371 (0.3%)
Renal Failure	1/371 (0.3%)
Renal Failure Acute	1/371 (0.3%)
Reproductive system and breast disorders
Female genital tract fistula	1/371 (0.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/371 (0.8%)
Respiratory Failure	3/371 (0.8%)
Pulmonary Embolism	2/371 (0.5%)
Pulmonary Haemorrhage	1/371 (0.3%)
Skin and subcutaneous tissue disorders
Angioedema	1/371 (0.3%)
Dermatitis	1/371 (0.3%)
Photosensitivity Reaction	1/371 (0.3%)
Rash	1/371 (0.3%)
Rash Maculo-Papular	1/371 (0.3%)
Vascular disorders
Deep Vein Thrombosis	1/371 (0.3%)
Other (Not Including Serious) Adverse Events
	Overall Trial
	Affected / at Risk (%)	# Events
Total	308/371 (83%)
Gastrointestinal disorders
Nausea	69/371 (18.6%)
Diarrhoea	42/371 (11.3%)
Vomiting	30/371 (8.1%)
Constipation	20/371 (5.4%)
General disorders
Fatigue	102/371 (27.5%)
Oedema Peripheral	41/371 (11.1%)
Pyrexia	37/371 (10%)
Injury, poisoning and procedural complications
Sunburn	48/371 (12.9%)
Investigations
Weight decreased	27/371 (7.3%)
Metabolism and nutrition disorders
Decreased Appetite	42/371 (11.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	136/371 (36.7%)
Myalgia	30/371 (8.1%)
Pain In Extremity	20/371 (5.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous Cell Carcinoma Of Skin	25/371 (6.7%)
Skin Papilloma	23/371 (6.2%)
Nervous system disorders
Headache	37/371 (10%)
Skin and subcutaneous tissue disorders
Rash	102/371 (27.5%)
Photosensitivity Reaction	62/371 (16.7%)
Alopecia	41/371 (11.1%)
Hyperkeratosis	29/371 (7.8%)
Dry Skin	26/371 (7%)
Palmar-plantar erythrodysaesthesia syndrome	23/371 (6.2%)
Pruritus	36/371 (9.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.