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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03800836




Registration number
NCT03800836
Ethics application status
Date submitted
7/01/2019
Date registered
9/01/2019
Date last updated
1/02/2019

Titles & IDs
Public title
A Study to Evaluate the Safety and Efficacy of Ipatasertib in Combination With Atezolizumab and Paclitaxel or Nab-Paclitaxel in Participants With Locally Advanced or Metastatic Triple-Negative Breast Cancer
Scientific title
A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Ipatasertib in Combination With Atezolizumab and Paclitaxel or Nab-Paclitaxel in Patients With Locally Advanced or Metastatic Triple-Negative Breast Cancer
Secondary ID [1] 0 0
CO40151
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ipatasertib
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Nab-Paclitaxel

Experimental: Paclitaxel Arm: Ipatasertib + Atezolizumab + Paclitaxel - Participants will receive ipatasertib orally daily on Days 1-21 of each 28 day cycle, and atezolizumab will be administered by intravenous (IV) infusion on Days 1 and 15 of each 28 day cycle. Paclitaxel will be administered by IV infusion on Days 1, 8, and 15 of each 28 day cycle. All patients in this study will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

Experimental: Nab-Paclitaxel Arm: Ipatasertib+Atezolizumab+Nab-Paclitaxel - Participants will receive ipatasertib orally daily on Days 1-21 of each 28 day cycle, and atezolizumab will be administered by IV infusion on Days 1 and 15 of each 28 day cycle. Nab-paclitaxel will be administered by IV infusion on Days 1, 8, and 15 of each 28 day cycle. All patients in this study will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.


Treatment: Drugs: Ipatasertib
Ipatasertib will be administered at a dose of 400 milligrams (mg) orally daily on Days 1-21 of each 28 day cycle.

Treatment: Drugs: Paclitaxel
Paclitaxel will be administered at a dose of 80 milligrams per square meter (mg/m^2) as IV infusion on Days 1, 8, and 15 of each 28 day cycle.

Treatment: Drugs: Atezolizumab
Atezolizumab will be administered by IV infusion at a fixed dose of 840 mg on Days 1 and 15 of each 28 day cycle.

Treatment: Drugs: Nab-Paclitaxel
Nab-paclitaxel will be administered by IV infusion at a dose of 100 mg/m^2 on Days 1, 8, and 15 of each 28 day cycle.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohort 1: Percentage of Participants with Objective Response (Complete Response [CR] or Partial Response [PR]), as Assessed by Investigator Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version (v) 1.1
Timepoint [1] 0 0
Baseline up to disease progression or treatment discontinuation, whichever occurs first (to approximately 12 months)
Primary outcome [2] 0 0
Cohort 1: Duration of Confirmed Objective Response, as Determined by the Investigator According to RECIST v1.1
Timepoint [2] 0 0
Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 12 months)
Secondary outcome [1] 0 0
Cohort 1: Progression-Free Survival, as Assessed by Investigator Based on RECIST v1.1
Timepoint [1] 0 0
Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 12 months)
Secondary outcome [2] 0 0
Cohort 1: Percentage of Participants who have an Objective Response (Complete or Partial), or Stable Disease for at least 24 weeks, as Assessed by Investigator Based on RECIST v1.1
Timepoint [2] 0 0
Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 12 months)
Secondary outcome [3] 0 0
Cohort 1: Overall Survival in All Participants
Timepoint [3] 0 0
Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 12 months)
Secondary outcome [4] 0 0
Cohort 1: Plasma Concentration of Ipatasertib
Timepoint [4] 0 0
At Day 1 and Day 15 of Cycles 1-3, and Day 1 of Cycle 4 (each cycle is 28 days)
Secondary outcome [5] 0 0
Cohort 1: Plasma Concentration of Ipatasertib's Metabolite (G-037720)
Timepoint [5] 0 0
At Day 1 and Day 15 of Cycles 1-3, and Day 1 of Cycle 4 (each cycle is 28 days)
Secondary outcome [6] 0 0
Cohort 1: Presence of Anti-Drug Antibody During Study Treatment
Timepoint [6] 0 0
At Day 1 and Day 15 of Cycles 1-3, and Day 1 of Cycle 4 (each cycle is 28 days)
Secondary outcome [7] 0 0
Cohort 1: Plasma Concentration of Atezolizumab
Timepoint [7] 0 0
At Day 1 and Day 15 of Cycles 1-3, and Day 1 of Cycle 4 (each cycle is 28 days)
Secondary outcome [8] 0 0
Cohort 1 and Cohort 2: Percentage of Participants with Adverse Events
Timepoint [8] 0 0
Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 12 months)

Eligibility
Key inclusion criteria
- Eastern Cooperative Oncology Group Performance Status of 0 or 1

- Adequate hematologic and organ function

- Life expectancy of at least 6 months

- For men and women of child bearing potential: agreement to remain abstinent or use
protocol defined contraceptive measures during the treatment period and for at least
28 days after the last dose of ipatasertib, 6 months after the last dose of
paclitaxel, and 5 months after the last dose of atezolizumab, whichever occurs later

- Histologically documented TNBC that is locally advanced or metastatic

- Measurable disease according to RECIST v1.1
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of malabsorption syndrome or other condition that would interfere with enteral
absorption or results in the inability or unwillingness to swallow pills

- Active infection

- History of or current evidence of HIV infection

- Known clinically significant history of liver disease

- Pregnant or breastfeeding

- Left ventricular ejection fraction < 50%

- Prior treatment with an Akt inhibitor

- History of or known presence of brain or spinal cord metastases

- Patients may have received prior neoadjuvant or adjuvant chemotherapy and/or radiation
treatment for early stage breast cancer, provided all chemotherapy was completed >= 12
months prior to Day 1 of Cycle 1

- Uncontrolled tumor related complications

- Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1

- History of Type I or Type II diabetes mellitus requiring insulin

- Uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia

- History of or active inflammatory bowel disease or active bowel inflammation

- Clinically significant lung disease

- Treatment with strong CYP3A inhibitors or strong CYP3A inducers

- Active or history of autoimmune disease or immune deficiency

- Prior allogeneic stem cell or solid organ transplantation

- History of hypersensitivity reactions to study drug or any component of the study drug
formulation

- Treatment with systemic immunostimulatory agents and immunosuppressive medication
treatment, or anticipation of need for systemic immunosuppressive medication during
the course of the study

- Grade >= 2 peripheral neuropathy

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St Vincents Hospital; Cardiopulmonary transplant Ambulatory Care Dept - Darlinghurst
Recruitment hospital [2] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Washington
Country [3] 0 0
France
State/province [3] 0 0
Angers
Country [4] 0 0
France
State/province [4] 0 0
Bordeaux
Country [5] 0 0
France
State/province [5] 0 0
Dijon
Country [6] 0 0
France
State/province [6] 0 0
Paris
Country [7] 0 0
France
State/province [7] 0 0
Villejuif CEDEX
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Spain
State/province [9] 0 0
Madrid
Country [10] 0 0
United Kingdom
State/province [10] 0 0
London
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Manchester
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase Ib, open-label, multicenter study evaluating the safety and efficacy of
ipatasertib in combination with atezolizumab and paclitaxel or nab-paclitaxel for patients
with locally advanced or metastatic triple-negative breast cancer (mTNBC) who have not
previously received chemotherapy in the advanced setting. Two triplets; ipatasertib in
combination with atezolizumab and paclitaxel (Paclitaxel arm) and ipatasertib in combination
with atezolizumab and nab-paclitaxel (Nab-Paclitaxel arm) are being evaluated for first-line
chemotherapy treatment for advanced TNBC. Cohort 1 will evaluate first-line chemotherapy
treatment in advanced TNBC patients and Cohort 2 will contain biopsy assessments of TNBC
patients who have progressed after at least one line of chemotherapy in the advanced setting.
Trial website
https://clinicaltrials.gov/show/NCT03800836
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: CO40151 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global.rochegenentechtrials@roche.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable