A 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

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2017-001548-36-ES
• Date of registration: 31/07/2017
• Prospective Registration: Yes
• Primary sponsor: Roche Farma S.A. (Soc.unipersonal)que realiza el ensayo en España y que actúa como representante de F.Hoffmann- La Roche
• Public title: A 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
• Scientific title: 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
• Date of first enrolment: 18/09/2017
• Target sample size: 450
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001548-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Canada, Costa Rica, Czech Republic, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Macedonia, the former Yugoslav Republic of, Mexico, Peru, Poland, Romania, Russian Federation, Singapore, Slovenia, Spain, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
General Inclusion Criteria
- Woman or man age =>18 years at the time of signing the Informed Consent Form
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Adequate hematologic and organ function
- Life expectancy of at least 6 months
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 28 days after the last dose of ipatasertib/placebo and 6 months after the last dose of paclitaxel, whichever occurs later
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 28 days after the last dose of ipatasertib or 6 months after the last dose of paclitaxel, whichever occurs later

Disease-Specific Inclusion Criteria
- Locally assessed, histologically documented TNBC or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Submission of a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or a minimum of 20 freshly cut unstained, serial tumor slides from the most recently collected tumor tissue for central molecular analysis. Cytologic or FNA samples are not acceptable. Tumor tissue from bone metastases that is subject to decalcification is not acceptable.
- Valid results from central testing confirming PIK3CA/AKT1/PTEN-altered status in tumor tissue by next-generation sequencing (NGS)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 360
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion criteria:
General Exclusion Criteria:
- Inability to comply with study and follow-up procedures
- 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 requiring antibiotics
- Known HIV infection
- Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis (e.g., positive for hepatitis B surface antigen [HBsAg] or hepatitis C virus [HCV] antibody at screening), current drug or alcohol abuse, or cirrhosis
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure during the course of the study
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 28 days after the last dose of ipatasertib/placebo and within 6 months after the last dose of paclitaxel, whichever occurs later
- New York Heart Association Class II, III, or IV heart failure; left ventricular ejection fraction <50%; or active ventricular arrhythmia requiring medication
- Current unstable angina or history of myocardial infarction within 6 months prior to Day 1 of Cycle 1
- Congenital long QT syndrome or screening QT interval corrected using Fridericia's formula (QTcF) >480 milliseconds
- History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
- Need for chronic corticosteroid therapy of >=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
- Treatment with approved or investigational cancer therapy within 14 days prior to Day 1 of Cycle 1

Disease-Specific Exclusion Criteria:
- History of or known presence of brain or spinal cord metastases, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments
- Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2– adenocarcinoma of the breast
- Unresolved, clinically significant toxicity from prior therapy
- For patients with HR+/HER2– breast cancer, endocrine therapy (alone or with approved targeted therapy such as CDK4/6 inhibitors or everolimus) must not be considered an appropriate option per local clinical guidelines
- Patients who have received palliative radiation treatment to peripheral sites (e.g., bone metastases) for pain control and whose last treatment was completed 14 days prior to Day 1 of Cycle 1 may be enrolled in the study if they have recovered from all acute, reversible effects (e.g., to Grade 1 or resolved by enrollment)
- Uncontrolled pleural effusion, pericardial effusion, or ascites
- Uncontrolled tumor-related pain
- Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1 except for appropriately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, or Stage I uterine cancer

Ipatasertib-Specific Exclusion Criteria:
- History of Type I or Type II diabetes mellitus requiring insulin
- Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
- History of or active inflammatory bowel disease or active

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Locally advanced or metastatic triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer or locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer with PIK3CA/AKT1/PTEN-altered tumor and no prior chemotherapy in the advanced setting
MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000020826
MedDRA version: 20.0 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 100000020819

Intervention(s)

Product Name: ipatasertib 100mg
Product Code: RO5532961
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ipatasertib
Current Sponsor code: RO5532961
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: ipatasertib 200mg
Product Code: RO5532961
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ipatasertib
Current Sponsor code: RO5532961
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Primary Outcome(s)

Primary end point(s): Investigator-assessed Progression free survival through the use of RECIST v1.1, or death from any cause, whichever occurs first

Main Objective: • To evaluate the efficacy of ipatasertib + paclitaxel compared with placebo + paclitaxel based on progression-free survival (PFS) defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurs first

Timepoint(s) of evaluation of this end point: Up to approximately 53 months, until disease progression, or lost to follow-up or consent withdrawal

Secondary Objective: • To evaluate the efficacy of ipatasertib + paclitaxel compared with placebo + paclitaxel based on Objective response rate (ORR), Duration of response (DOR), Clinical benefit rate, Overall survival (OS)
• To evaluate patient-reported outcomes (PRO) of global health status (GHS)/ health-related quality of life (HRQoL) associated with ipatasertib + paclitaxel compared with placebo + paclitaxel
• To evaluate the safety of ipatasertib + paclitaxel compared with placebo + paclitaxel
• To characterize the pharmacokinetics of ipatasertib and its metabolite (G-037720) when administered in combination with paclitaxel

Secondary Outcome(s)

Secondary end point(s): 1. Objective response rate
2. Duration of response
3. Clinical benefit rate
4. Overall survival
5. Mean and mean changes from baseline GHS/HRQoL score as measured by the GHS/HRQoL scale
6. Incidence of adverse events as assessed by the investigator, with severity determined through the use of NCI CTCAE v4.0
7. Incidence of prespecified adverse events
8. Change from baseline in targeted vital signs
9. Change from baseline in targeted clinical laboratory test results
10. Plasma concentration of ipatasertib and G-037720 at specified timepoints for analysis using population PK methodology

Timepoint(s) of evaluation of this end point: 1-3. Up to approximately 53 months, until disease progression or death
4-5. Up to approximately 53 months, until death or lost to follow-up or consent withdrawal
6. Up to 28 days after the last dose of study treatment or initiation of new anticancer therapy, except for Serious Adverse Events considered related to study treatment
7-9. Up to 28 days after the last dose of study treatment or initiation of new anticancer therapy
10. Day 1 and Day 15 of Cycle 1, and on Day 15 of Cycle 3

Secondary ID(s)

CO40016

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd