Clinical Trial for metastatic melanoma patients. (skin cancer)

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2012/07/002756
• Date of registration: 02-07-2012
• Prospective Registration: Yes
• Primary sponsor: Roche Products India Pvt Ltd
• Public title: Clinical Trial for metastatic melanoma patients. (skin cancer)
• Scientific title: Open-label, multicenter, multi-national, phase III study to assess the safety of RO5185426 in patients with BRAF V600 mutation-positive (identified by the cobas 4800 BRAF V600 Mutation Test) metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV; AJCC).
• Date of first enrolment: 02-07-2012
• Target sample size: 900
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=4472
• Study type: Interventional
• Study design: Non-randomized, Active Controlled Trial; Method of generating randomization sequence:Not Applicable Method of allocation concealment:Not Applicable Blinding and masking:Not Applicable
• Phase: Phase 3

Countries of recruitment

Austria, Brazil, Canada, Czech Republic, Denmark, Greece, India, Ireland, Israel, Malta, New Zealand, Portugal, Slovakia, Slovenia, Switzerland, United Kingdom, United States of America

Contacts

• Name: Dr Rupesh Pophale

• Name: Dr Rupesh Pophale

Key inclusion & exclusion criteria

Inclusion criteria: Inclusion Criteria:

1. Male or female patients >= 16 years of age

2. Patients with histologically confirmed

metastatic melanoma (surgically incurable

and unresectable stage IIIC or stage IV;

AJCC) with documented BRAF V600 mutation

determined by the cobas® 4800 BRAF V600

Mutation Test prior to administration of

RO5185426. Unresectable stage IIIC disease

must have confirmation from a surgical

oncologist

3. Patients with either measurable or non-

measurable disease(RECIST Version 1.1)

4. Patients may or may not have received prior

systemic therapy for metastatic melanoma

5. Eastern Cooperative Oncology Group (ECOG)

performance status (PS) of 0-2

6. Patients must have recovered from all side

effects of their most recent systemic or

local treatment for metastatic melanoma

7. Adequate hematologic, renal and liver

function as defined by the following

laboratory values performed within 7 days

prior to first dose of RO5185426:

• Absolute neutrophil count (ANC) >= 1.5 x

109/L

• Platelet count >= 100 x 109/L

• Hemoglobin >= 9 g/dL

• Serum creatinine <= 1.5 times upper limit

of normal (ULN) or creatine clearance

(CrCl) > 50 mL/hr by Cockroftâ??Gault formula

• Aspartate aminotransferase (AST [SGOT]) and

alanine aminotransferase (ALT [SGPT]) <= 2.5

times ULN (<= 5times ULN if considered due

to tumor)

• Serum bilirubin <= 1.5 times ULN

• Alkaline phosphatase <= 2.5 times ULN (<=

5times ULN if considered due to tumor)

8. Negative serum pregnancy test within 7 days

prior to commencement of dosing in

premenopausal women. Women of non-

childbearing potential may be included if

they are either surgically sterile or have

been postmenopausal for >=1 year.

9. Fertile men and women must use an effective

method of contraception during treatment and

for at least 6 months after completion of

treatment as directed by their physician.

Effective methods of contraception are

defined as those which result in a low

failure rate (i.e. less than 1% per year) when

used consistently and correctly (for example

implants, injectables, combined oral

contraception or intra-uterine devices). At

the discretion of the investigator, acceptable

methods of contraception may include total

abstinence in cases where the lifestyle of

the patient ensures compliance.[Periodic

abstinence (e.g. calendar, ovulation,

symptothermal, postovulation methods) and

withdrawal are not acceptable methods of

contraception.]

10.Absence of any psychological, familial,

sociological or geographical condition

potentially hampering compliance with the

study protocol and follow-up schedule; those

conditions should be discussed with the

patient before trial entry

11.Signed informed consent must be obtained

prior to performing any study-related

procedures (includ
Exclusion criteria: 1. Evidence of symptomatic CNS lesions as

determined by investigator (patients with

radiographically stable, asymptomatic lesions

previously irradiated or surgically resected

are eligible)

2. Patients with a previous malignancy (other

than melanoma) within the past 2 years are

excluded except patients with treated and

controlled basal or squamous cell carcinoma

(SCC) of the skin or carcinoma in-situ of the

cervix. Isolated elevation in prostate-

specific antigen in absence of radiographic

evidence of metastatic prostate cancer is

allowed

3. Concurrent administration of any anti-cancer

therapies (e.g. chemotherapy, other targeted

therapy, experimental drug, etc) other than

those administered in this study

4. Known hypersensitivity to RO5185426 or

another BRAF inhibitor

5. Pregnant or lactating women

6. Refractory nausea and vomiting,malabsorption,

external biliary shunt, or significant bowel

resection that would preclude adequate

absorption. Patients must be able to swallow

tablets

7. Any of the following within the 6 months

prior to first RO5185426 administration:

myocardial infarction, severe/unstable

angina, symptomatic congestive heart failure,

cerebrovascular accident or transient

ischemic attack, pulmonary embolism,

hypertension not adequately controlled

by current medications

8. History of congenital long QT syndrome,

history or presence of clinically significant

ventricular or atrial dysrhythmias >= Grade 2

(NCI CTCAE Version 4.0)

9. Corrected QT (QTc) interval >= 450 msec at

baseline

10.Uncontrolled medical illness (such as

infection requiring treatment with

intravenous (IV) antibiotics)

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Patients with histologically confirmed metastatic melanoma harboring the BRAF V600 mutation as determined by the cobas® 4800 BRAF V600 Mutation Test.

Intervention(s)

Intervention1: Vemurafenib (RO5185426): -
Intervention2: Vemurafenib: RO5185426 is a low molecular weight, orally available, selective inhibitor of the
activated form of the BRAF serine-threonine kinase enzyme, which is commonly found
in malignant melanoma. In vitro biochemical and cell-based assays have confirmed a
high degree of selectivity of RO5185426 for the oncogenic BRAF V600E kinase.
It is equipotent against CRAF
(44 nM) and 3-fold less potent against BRAF wild type (110 nM). In a panel of 58
kinases, RO5185426 had an IC50 1 μM for only 1 kinase (BRK kinase) outside the
BRAF family. RO5185426 was also screened against 63 receptors in 8 different families.
At 10 μM, RG7204 showed marginal activity (20â??24% inhibition) against 4 receptors and was inactive against the other 59 targets.
Dose: 960mg B.I.D
Route of administration: Oral
Frequency: every cycle wherein One cycle
of therapy is defined as 28 days of treatment.
Intotal 8 cycles.
Control Intervention1: NA: NA

Primary Outcome(s)

To evaluate the safety and tolerability of RO5185426 in

patients with metastatic melanoma (surgically incurable and

unresectable stage IIIC or stage IV; AJCC) harboring the BRAF V600 mutation.Timepoint: N/A

Secondary Outcome(s)

To evaluate the efficacy of RO5185426 as overall

response rates (ORRs) determined by the investigator (RECIST,

Version 1.1) as allowed by local regulatory requirements.Timepoint: Screening, Cycle 3, Cycle 5 and End of the study.

Secondary ID(s)

NCT01307397

MO25515

Source(s) of Monetary Support

Roche Products India Pvt. Ltd.

Ethics review

Status: Approved
Approval date: 19/01/2012
Contact:

Institutional Review Board, Rajiv Gandhi Cancer Institute & Research Centre

Status: Approved
Approval date: 16/04/2012
Contact:

Manavata Clinical Research Institute Professional Ethics Committee

Status: Approved
Approval date: 26/06/2012
Contact:

Chhatrapati Shahuji Maharaj Institutional Ethics Committee

Status: Approved
Approval date: 16/07/2012
Contact:

Institutional Review Board-Christian Medical College

Status: Approved
Approval date: 30/07/2012
Contact:

Institutional Ethics Committee-BasavaTarakam Indo-American Cancer Hospital & Research Institute

Status: Approved
Approval date: 17/08/2012
Contact:

Regional Cancer Centre Human Ethics Committee

Status: Approved
Approval date: 15/04/2014
Contact:

Institutional Ethics Committee, Tata Memorial Hospital