| CTRI Number |
CTRI/2019/05/019047 [Registered on: 10/05/2019] Trial Registered Prospectively |
| Last Modified On: |
11/02/2020 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A clinical trial of ipatasertib in combination with paclitaxel versus placebo and paclitaxel in patients with specific tumor alteration, Locally Advanced or Metastatic, Triple Negative Breast cancer or Hormone Receptor – Positive, HER2 – Negative Breast Cancer |
|
Scientific Title of Study
|
A Double Blind, Placebo- Controlled, Randomized Phase III Study of IPATASERTIB in combination with Paclitaxel As a treatment for patients with PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple Negative Breast cancer or Hormone Receptor – Positive, HER2 – Negative Breast Cancer |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Sudeep Gupta |
| Designation |
Professor of Medical Oncology |
| Affiliation |
Tata Memorial Hospital |
| Address |
Dr. E Borges Road, Parel East
Professor of Medical Oncology and Director, (CRC) ACTREC,
Tata Memorial Centre, Tata Memorial Hospital,
Room no. 1109, 11th Floor, Homi Bhabha block
Dr. Ernest Borges Marg, Parel, Mumbai-400012
Mumbai (Suburban)
MAHARASHTRA
400012
India |
| Phone |
|
| Fax |
|
| Email |
sudeepgupta04@yahoo.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Sandeep Bhatia |
| Designation |
Associate Director - Medical Affairs |
| Affiliation |
Roche Products (India) Pvt. Ltd. |
| Address |
1503, 15th Floor, The Capital Bandra Kurla Complex, Bandra (East)
Mumbai (Suburban)
MAHARASHTRA
400051
India |
| Phone |
022-33941414 |
| Fax |
022-33941054 |
| Email |
sandeep.bhatia@roche.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Jitendra Soni |
| Designation |
Clinical Operations Manager & Local Vendor Manager |
| Affiliation |
Roche Products (India) Pvt. Ltd. |
| Address |
1503, 15th Floor, The Capital Bandra Kurla Complex, Bandra (East)
1503, 15th Floor, The Capital Bandra Kurla Complex, Bandra (East)
Mumbai (Suburban)
MAHARASHTRA
400051
India |
| Phone |
22-33941426 |
| Fax |
022-33941054 |
| Email |
jitendra.soni@roche.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
F HoffmannLa Roche Ltd |
| Address |
Grenzacherstrasse 124, CH-4070 Basel, Switzerland
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Roche Products India Pvt Ltd |
1503, 15th Floor, The Capital Bandra Kurla Complex, Bandra (East) Mumbai, MAHARASHTRA-400 051, India |
|
|
Countries of Recruitment
|
Brazil
Australia
Belgium
Canada
Chile
China
Costa Rica
Czech Republic
France
Germany
Greece
Hungary
India
Italy
Mexico
Peru
Poland
Republic of Korea
Russian Federation
Singapore
Slovenia
Spain
Taiwan
Ukraine
United Kingdom
United States of America
Japan |
|
Sites of Study
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Minish Jain |
Grant Medical Foundation Ruby Hall Clini |
No 40, Sassoon Road, Pune – 411001, Maharashtra , India
Pune
MAHARASHTRA |
9823133390
minishjain009@gmail.com |
| Dr Ashish Kaushal |
HCG cancer center |
Sola science city road, Near Sola Bridge, Off S G Highway, Ahmedabad 380060
Ahmadabad
GUJARAT |
9978297842
drashish4@yahoo.co.in |
| Dr Manish Singhal |
Indraprashtha Apollo Hospitals |
Sarita Vihar, New Delhi- 110076
New Delhi
DELHI |
9818736533
singhaloncocare@yahoo.co.in |
| Dr RangaRao Rangaraju |
Max Super Specialty Hospital |
FC – 50 C & D Block, Shalimar Bagh, New Delhi – 110088
New Delhi
DELHI |
9810297787
rangaraodr@gmail.com |
| DrDinesh Chandra Doval |
Rajiv Gandhi Cancer Institute & Research Centre |
Sector 5, Rohini, New Delhi – 110085, India
North West
DELHI |
1147022222
ddoval07@gmail.com |
| Dr Sudeep Gupta |
Tata Memorial Centre, Tata Memorial Hospital |
Room no. 1109, 11th Floor, Homi Bhabha Block, Tata Memorial Centre, Tata Memorial Hospital, Dr. Ernest Borges Marg, Parel, Mumbai - 400012, Maharashtra, India
Mumbai
MAHARASHTRA |
9821298642
sudeepgupta04@yahoo.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| HCG Multi Specialty Ethics Committee |
Approved |
| Institution Ethics Committee (IEC I / II) |
Approved |
| Institutional Ethics Committee Poona Medical Research Foundation |
Approved |
| Institutional Ethics Committee – Clinical Studies |
Approved |
| Institutional Review Board |
Submittted/Under Review |
| Max Healthcare Ethics Committee |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Ipatasertib |
Ipatasertib 400mg Oral QD (Day 1 to 21 of each 28 day cycle) |
| Comparator Agent |
Paclitaxel |
Paclitaxel 80mg/m2 ; IV infusion on days 1, 8 and 15 of each 28 day cycle |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
Informed Consent
Woman or man age 18 years and above
Inoperable locally advanced/metastatic breast cancer (LA/MBC), Histologically documented TNBC or HR+/HER2– adenocarcinoma and suitable for taxane monotherapy
At least 12 month disease-free interval from last chemotherapy/radiation treatment for early BC.
Eastern Cooperative Oncology Group Performance Status of 0 or 1
Life expectancy of at least 6 months
Measurable disease according to RECIST v1.1
formalin-fixed, paraffin-embedded tumor (FFPE) tissue, [PIK3CA/AKT1/PTEN-altered status and central ctDNA]
Adequate hematologic and organ function within 14 days before the first study treatment
Fasting total serum glucose ≤ 150 mg/dL and HbA1C ≤ 7.5%,
|
|
| ExclusionCriteria |
| Details |
Active infection requiring systemic anti-microbial treatment, Known HIV infection, Active viral or other Hepatitis
New York Heart Association Class II, III, or IV heart failure, LVEF less than 50%
History of or known presence of brain or spinal cord metastases by CT/ MRI
Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2– adenocarcinoma of the breast
Uncontrolled pleural effusion, pericardial effusion, or ascites
History of or active Inflammatory bowel disease, Lung disease
Prior treatment with an AKT inhibitor (Prior PI3K or mTOR inhibitors are allowed)
No uncontrolled disease/unresolved toxicity or clinically relevant condition which may contraindicate use of an investigational drug
|
|
|
Method of Generating Random Sequence
|
Stratified block randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Double Blind Double Dummy |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Investigator-assessed PFS |
from randomization to
the first occurrence of disease progression, as
determined locally by the investigator through
the use of RECIST v1.1, or death from any
cause, whichever occurs first |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| OS, ORR, DoR, CBR, patient-reported pain (cohort B only) and HRQoL |
ORR-CR or
PR on two consecutive occasions more than or equal to 4 weeks apart, as determined locally by the investigator |
|
|
Target Sample Size
|
Total Sample Size="450"
Sample Size from India="10"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
15/10/2019 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
06/01/2018 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="3"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
Not applicable as of now |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
This protocol
encompasses two studies, or cohorts, of different patient populations that will
independently evaluate the safety, efficacy, and pharmacokinetics of ipatasertib
in combination with paclitaxel (ipatasertib + paclitaxel) compared with placebo
plus paclitaxel (placebo + paclitaxel) in patients with PIK3CA/AKT1/PTEN-altered tumors.
One cohort will be a
first-line treatment in patients with locally advanced or metastatic
triple-negative breast cancer (TNBC),
and the second will be
a first-chemotherapy treatment in patients with advanced hormone receptor-positive, human
epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer who are
not appropriate candidates for endocrine therapy.
Patients will be
screened for PIK3CA/AKT1/PTEN-altered tumors and
will be allocated to one of the cohorts based on hormone-receptor status.
HER2-positive patients are not eligible.
The reason that the two
patient populations will be evaluated separately is that TNBC and HR+/HER2- breast cancers have
different biologics that manifest clinically in different prognoses and
response to treatment, and molecularly with distinctly different molecular
profiles with dissimilar oncogenic drivers. The
two populations have
different prevalences and progression-free survival (PFS) and overall survival
(OS) expectations, and thus different enrollment and analysis timelines.
The two independent
target patient populations for this study are premenopausal and postmenopausal
female and male patients with measurable, locally advanced or metastatic TNBC
and HR+/HER2- breast cancer who have
not received chemotherapy in either of these settings. Patients must be
appropriate candidates for taxane monotherapy.
In particular, patients
with HR+/HER2- breast cancer should be
suitable for treatment with chemotherapy, chemotherapy is allowed, provided it
has been concluded at least 12 months before disease recurrence.
Patients with PIK3CA/AKT1/PTEN-altered tumors will be
assigned to Cohort A (TNBC) or Cohort B (HR+/HER2- breast cancer) based on
their hormone receptor status (as evaluated locally, or on study, only if local
evaluation is not available, with additional slides submitted for this purpose)
and randomized with a 2:1 ratio to the experimental versus control arm. All primary,
secondary, exploratory, and safety objectives will be assessed independently
for each cohort (i.e., Cohort A: patients with TNBC with PIK3CA/AKT1/PTEN-altered tumors and
Cohort
B: patients with HR+/HER2- breast cancer with PIK3CA/AKT1/PTEN-altered tumors).
The primary endpoint
for the Cohort A (TNBC) is PFS. The primary endpoint for Cohort B (HR+/HER2- breast cancer) is also
PFS. The primary analysis for each cohort will be independent and triggered by
cohort-specific events and will also be independent of the readout of the other
cohort. The secondary endpoints for each cohort will be tested if the primary analysis
of the respective PFS reaches statistical significance at the level of 5%. |