| CTRI Number |
CTRI/2012/07/002756 [Registered on: 02/07/2012] Trial Registered Prospectively |
| Last Modified On: |
24/11/2016 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Biological |
| Study Design |
Non-randomized, Active Controlled Trial |
|
Public Title of Study
|
Clinical Trial for metastatic melanoma patients.
(skin cancer) |
|
Scientific Title of Study
|
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). |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| MO25515 |
Protocol Number |
| NCT01307397 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
|
| Affiliation |
|
| Address |
|
| Phone |
|
| Fax |
|
| Email |
|
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Rupesh Pophale |
| Designation |
Medical Manager |
| Affiliation |
|
| Address |
Roche Products (India) Pvt.Ltd. "The View", 2nd Floor, 165, Dr. Annie Besant Road, Worli.
Mumbai
MAHARASHTRA
400018
India |
| Phone |
02224941414 |
| Fax |
02224949500 |
| Email |
rupesh.pophale@roche.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Rupesh Pophale |
| Designation |
Medical Manager |
| Affiliation |
|
| Address |
Roche Products (India) Pvt.Ltd.
"The View", 2nd Floor,
165, Dr. Annie Besant Road,
Worli.
Mumbai
MAHARASHTRA
400018
India |
| Phone |
02224941414 |
| Fax |
02224949500 |
| Email |
rupesh.pophale@roche.com |
|
|
Source of Monetary or Material Support
|
| Roche Products India Pvt. Ltd. |
|
|
Primary Sponsor
|
| Name |
Roche Products India Pvt Ltd |
| Address |
The View,2nd Floor,
165, Dr Annie Besant Road,
Worli, Mumbai-400018
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Austria
Brazil
Canada
Czech Republic
Denmark
Greece
Ireland
Israel
Malta
New Zealand
Portugal
Slovakia
Slovenia
Switzerland
United Kingdom
United States of America
India |
Sites of Study
Modification(s)
|
| No of Sites = 7 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Senthil Rajappa |
Basavatarakam Indo-American Cancer Hospital & Research Institute |
Clinical Research Room, 4th floor, Road No 14, Banjara Hills,
Hyderabad
ANDHRA PRADESH |
09849213102
siddharth142@sify.com |
| Dr Vijay Kumar |
Chhatrapati Shahuji Maharaj Medical University |
Chowk
Lucknow
UTTAR PRADESH |
09935383666
drvkumar2007@gmail.com |
| Dr Raju Chacko |
Christian Medical College |
3rd floor, Ida Schudder Road,
Vellore
TAMIL NADU |
09443250124
rchacko@cmcvellore.ac.in |
| Dr Rajnish Nagarkar |
Curie Manavata Cancer Centre |
2nd Floor, Opp. Mahamarg Bus Stand, Mumbai Naka,
Nashik
MAHARASHTRA |
0253-2594866
drraj@mcrinasik.com |
| Dr Ullas Batra |
Rajiv Gandhi Cancer Institute and Research Centre |
Room No. 2251, Sector–V, Rohini,
New Delhi
DELHI |
09711080001
ullasbatra@gmail.com |
| Dr P G Jayaprakash |
Regional Cancer Centre |
2nd floor, Radiation Oncology
Thiruvananthapuram
KERALA |
09447043191
pgjprakash@yahoo.com |
| Dr Sudeep Gupta |
Tata Memorial Hospital |
Research Room, Annex Bldg, Dr Ernest Borges Marg, Parel
Mumbai
MAHARASHTRA |
09821298642
sudeepgupta04@yahoo.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 7 |
| Name of Committee |
Approval Status |
| Chhatrapati Shahuji Maharaj Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee, Tata Memorial Hospital |
Approved |
| Institutional Ethics Committee-BasavaTarakam Indo-American Cancer Hospital & Research Institute |
Approved |
| Institutional Review Board, Rajiv Gandhi Cancer Institute & Research Centre |
Approved |
| Institutional Review Board-Christian Medical College |
Approved |
| Manavata Clinical Research Institute Professional Ethics Committee |
Approved |
| Regional Cancer Centre Human Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Patients with histologically confirmed metastatic melanoma
harboring the BRAF V600 mutation as determined by the cobas® 4800 BRAF V600 Mutation Test., |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
NA |
NA |
| Intervention |
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 (20–24% 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. |
|
|
Inclusion Criteria
|
| Age From |
16.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
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 Cockroft–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 (including tumor testing for the
V600 BRAF mutation) |
|
| ExclusionCriteria |
| Details |
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) |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
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. |
N/A |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
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. |
Screening, Cycle 3, Cycle 5 and End of the study. |
|
|
Target Sample Size
|
Total Sample Size="900"
Sample Size from India="12"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
02/07/2012 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
01/03/2011 |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
NA |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Summary
Metastatic melanoma represents a major clinical challenge as it is an essentially incurable disease with few satisfactory treatment options. Current first-line treatment options have yielded low response rates and no evidence of impact on survival. In the second-line setting, no treatment is considered effective and response rates to agents after first-line failure are very low (section 1.1.1).
RO5185426 is a highly selective inhibitor of the oncogenic BRAF kinase which has been identified in a large number of malignant melanomas. Results from Phase I and II studies have shown that RO5185426 induces high response rates in patients with metastatic melanoma carrying the V600E BRAF mutation (section 1.1.3). Results from the phase 3 study show an OS and PFS benefit in patients with unresectable IIIC or stage IV metastatic melanoma. These data indicate that RO5185426 might be an effective treatment option in this patient population with no currently available satisfactory treatment options. The purpose of this multicenter, early access study is to make RO5185426 available to a larger number of patients than could otherwise be treated in registration trials and who are without satisfactory treatment options. The primary objective of this study will be to evaluate the safety of RO5185426 in patients with unresectable IIIC or stage IV metastatic melanoma positive for the V600 BRAF mutation (identified by the cobas® 4800 BRAF V600 Mutation Test).
Study Overview:
This is an open-label, multicenter, multi-national, expanded access study of RO5185426 in patients with BRAF V600 mutation-positive (identified by the cobas ® 4800 BRAF V600 Mutation Test) metastatic melanoma who may or may not have received prior
therapy for metastatic melanoma. The primary objective of this study is to assess the safety and tolerability of RO5185426. The study population will consist of patients at least 16 years of age with histological confirmed diagnoses of metastatic melanoma harboring the BRAF V600 mutation, as determined by cobas ® 4800 BRAF V600 Mutation Test. Patients with measurable and/or non-measurable disease (as defined by RECIST 1.1) are eligible for enrollment in this trial. Patients may or may not have received prior therapy for metastatic melanoma. The trial will consist of a screening period (Day –28 to Day 1), a treatment phase, and an end of study/follow up. Day 1 of the study will be defined as the first day a patient receives RO5185426. One cycle of therapy is defined as 28 days of treatment. |