Breast CancerPhase 1NCT00960960

A Study of PI3-Kinase Inhibitor GDC-0941 in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, and With Letrozole, in Participants With Locally Recurrent or Metastatic Breast Cancer

A Phase 1 study testing Bevacizumab, Pictilisib and Letrozole in people with Breast Cancer, run by Genentech, Inc. at 5 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Breast Cancer
What is being tested?: Bevacizumab, Pictilisib and Letrozole
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 71 participants
Where: 5 sitesin 3 countries
Study dates: Aug 2009to Dec 2015
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease
Adequate organ and bone marrow function as assessed by laboratory tests
Evaluable disease or disease measurable per RECIST
Agreement to use an effective form of contraception for the duration of the study

Who cannot join

History of malabsorption syndrome or other condition that would interfere with enteral absorption
Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytic agents
Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, radiotherapy, or hormonal therapy) within 4 weeks or 5 half-lives (whichever is shorter) of the first dose of study treatment
Uncontrolled current illness
Active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis)
Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus

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Known HIV infection
New York Heart Association (NYHA) Class II or greater congestive heart failure
Active ventricular arrhythmia requiring medication
Pregnancy, lactation, or breastfeeding
Known significant hypersensitivity to study drugs or excipients
History of arterial thromboembolic disease within 6 months of first study treatment
No more than two prior chemotherapy regimens for metastatic disease

Trial locations and contacts

5 sites in 3 countries.

Country

City, postcode or hospital

5 sites in 3 countries

United States3 sites

Study site
Boston, Massachusetts, 02115
Study site
Nashville, Tennessee, 37232
Study site
Peoria, Illinois, 61615

Other trials in United States

Belgium1 site

Study site
Leuven, 3000

Other trials in Belgium

Italy1 site

Study site
Milan, Lombardy, 20133

Other trials in Italy

About this study

Official title: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of PI3-Kinase Inhibitor GDC-0941 (Pictilisib) in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, and With Letrozole in Patients With Locally Recurrent Or Metastatic Breast Cancer

This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of oral (PO) pictilisib administered with letrozole or intravenous (IV) paclitaxel with and without IV bevacizumab or IV trastuzumab in participants with locally recurrent or metastatic breast cancer. The study consists of three parts. Part 1 (pictilisib will be administered in 21+7 schedule along with paclitaxel and/or bevacizumab), Part 2 (pictilisib will be administered in 5+2 schedule along with paclitaxel and/or bevacizumab or trastuzumab) and Part 3 (pictilisib will be administered in combination with letrozole). Part 1 and Part 2 consists of two stages; a dose escalation stage and a cohort-expansion stage.

Conditions: Breast Cancer
Being tested: Bevacizumab, Pictilisib, Letrozole, Paclitaxel, Trastuzumab
Keywords: MBC, PI3K, Avastin, Herceptin
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BevacizumabDrug
Also called Avastin
Bevacizumab will be administered IV at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle.
PictilisibDrug
Also called GDC-0941
Pictilisib will be administered PO QD on escalating doses.
LetrozoleDrug
Letrozole will be administered PO at a dose of 2.5 mg QD for for each 28-day cycle.
PaclitaxelDrug
Paclitaxel will be administered IV at a dose of 90 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle.
TrastuzumabDrug
Also called Herceptin
Trastuzumab will be administered IV at a dose of 2-4 mg/kg on on Days 1, 8, 15, and 22 of each 28-day cycle.

Study groups in NCT00960960
Study group	Role	What they receive
Part 1 (Cohort 1-2): Pictilisib 60 mg +Paclitaxel +Bevacizumab	Experimental	Pictilisib 60 mg will be administered orally (PO) once daily (QD) for 21 consecutive days of each 28-day cycle (21+7 schedule) with paclitaxel 90 milligrams per meter square (mg/m^2) intravenously (IV) on Days 1, 8, and 15 and bevacizumab 10 milligrams per kilogram (mg/kg) IV on Days 1 and 15 of each 28-day cycle. In Cohort 1 (Part 1), pictilisib will be evaluated with paclitaxel only; participants in Cohort 1 (Part 1) will be eligible to receive bevacizumab starting at Cycle 2. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity. Receives: Drug: Bevacizumab; Drug: Pictilisib; Drug: Paclitaxel
Part 1 (Cohort 3): Pictilisib 100 mg+ Paclitaxel + Bevacizumab	Experimental	Pictilisib 100 mg will be administered PO QD for 21 consecutive days of each 28-day cycle (21+7 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity. Receives: Drug: Bevacizumab; Drug: Pictilisib; Drug: Paclitaxel
Part 2 (Arm A: Cohort 1a): Pictilisib 165 mg + Paclitaxel	Experimental	Pictilisib 165 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity Receives: Drug: Pictilisib; Drug: Paclitaxel
Part 2 (Arm A: Cohort 2a): Pictilisib 250 mg + Paclitaxel	Experimental	Pictilisib 250 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity. Receives: Drug: Pictilisib; Drug: Paclitaxel
Part 2 (Arm A: Cohort 3a): Pictilisib 330 mg + Paclitaxel	Experimental	Pictilisib 330 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity. Receives: Drug: Pictilisib; Drug: Paclitaxel
Part2(Arm B:Cohort 1b):Pictilisib 200mg+Paclitaxel+Bevacizumab	Experimental	Pictilisib 200 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity. Receives: Drug: Bevacizumab; Drug: Pictilisib; Drug: Paclitaxel
Part2(Arm B:Cohort 2b):Pictilisib 250mg+Paclitaxel+Bevacizumab	Experimental	Pictilisib 250 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity. Receives: Drug: Bevacizumab; Drug: Pictilisib; Drug: Paclitaxel
Part2(Arm B:Cohort 3b):Pictilisib 260mg+Paclitaxel+Bevacizumab	Experimental	Pictilisib 260 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity. Receives: Drug: Bevacizumab; Drug: Pictilisib; Drug: Paclitaxel
Part2(Arm C:Cohort 1c):Pictilisib 180mg+Paclitaxel+Trastuzumab	Experimental	Pictilisib 180 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and trastuzumab 2-4 mg/kg IV on Days 1, 8, 15, and 22 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity. Receives: Drug: Pictilisib; Drug: Paclitaxel; Drug: Trastuzumab
Part2(Arm C:Cohort 2c):Pictilisib 260mg+Paclitaxel+Trastuzumab	Experimental	Pictilisib 260 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and trastuzumab 2-4 mg/kg IV on Days 1, 8, 15, and 22 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity. Receives: Drug: Pictilisib; Drug: Paclitaxel; Drug: Trastuzumab
Part 3: Pictilisib 260 mg + Letrozole	Experimental	Pictilisib 260 mg will be administered PO QD continuously with letrozole 2.5 mg PO QD for each 28-day cycle. Study treatment will continue until disease progression or unacceptable toxicity. Receives: Drug: Pictilisib; Drug: Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Measured: First treatment cycle (Day 1 up to Day 29)
Maximum Tolerated Dose (MTD) of Pictilisib
Measured: First treatment cycle (Day 1 up to Day 29)
Recommended Phase II Dose (RP2D) of Pictilisib
Measured: Baseline up to 54.2 months
Number of Cycles of Each Component of the Treatment Regimen
Measured: Baseline up to 54.2 months
Dose Intensity of Each Component of the Treatment Regimen
Measured: Baseline up to 54.2 months

Secondary outcomes (13)

Minimum Observed Plasma Concentration (Cmin) of Pictilisib
Measured: Parts 1 and 2 (dose escalation): predose (0 hours [h]) on Day (D) 1,3,16, and 17 of Cycle (C) 1. Part 2 (dose expansion): predose (0h) on D3,16,17 of C1; Part 3: Predose (0h) on D1 of C1, C2-6, C≥7, D15 of C1 (cycle length=28 days; up to 54.5 months)
Cmin of Paclitaxel
Measured: Parts 1 and 2 (dose escalation): pre-paclitaxel infusion (0 h) on D2 and D16 of C1. Part 2 (dose expansion): pre-paclitaxel infusion (0 h) on D1 and D16 of C1 (cycle length=28 days)
Cmin of Letrozole
Measured: Part 3: Predose (0h) on D1 of C1, C2-6, C≥7, D15 of C1 (cycle length=28 days; up to 54.5 months)
Area Under the Curve From Time Zero to Last Measurable Concentrations (AUClast) of Pictilisib
Parts 1 and 2 (dose escalation): predose (0 h) and 1,2,3,6 h postdose on D1 and D16 of C1, 24h postdose on D1 of C1; predose (0h) on D3,17 of C1; study completion (up to 55.5 months). Part 2 (dose expansion): predose (0h) and 1,2,3,6h postdose on D16 of C1; predose (0h) on D3, D17 of C1; study completion (up to 55.5 months). Part 3: 3h postdose on D1 of C1; 1,2,3,4,8h postdose on D15 of C1; Predose (0h) on D1 of C1, C2-6, C≥7, D15 of C1 (cycle length=28 days; up to 54.5 months)
Measured: Parts 1 and 2: D1,D3,D16,D17 of C1; study completion. Part 2: D3,D16, D17 of C1; study completion. Part 3: D15 of C1; D1 of C1 to C6, C≥7 (cycle length=28 days; up to 54.5 months) [detailed timeframe is provided in endpoint description]
AUClast of Paclitaxel
Parts 1 and 2 (dose escalation): pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 2,4,6,24 h post-paclitaxel infusion on D2 and D16 of C1; study completion (up to 55.5 months). Part 2 (dose expansion): pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 1,2,3,6,24 h post-paclitaxel infusion on D1 of C1; pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 2, 4, 6, 24 h post-paclitaxel infusion on D16 of C1; study completion (cycle length=28 days; up to 55.5 months)
Measured: Parts 1 and 2 (dose escalation): D2 and D16 of C1; study completion. Part 2 (dose expansion): D1 and D16 of C1; study completion (cycle length=28 days; up to 55.5 months) [detailed timeframe is provided in endpoint description]
AUClast of Letrozole
Measured: Part 3: 1,2,3,4,8h postdose on D15 of C1; Predose (0h) on D1 of C1, C2-6, C≥7, D15 of C1 (cycle length=28 days; up to 54.5 months)
Maximum Observed Plasma Concentration (Cmax) of Pictilisib
Parts 1 and 2 (dose escalation): predose (0 h) and 1,2,3,6 h postdose on D1 and D16 of C1, 24h postdose on D1 of C1; predose (0h) on D3,17 of C1; study completion (up to 55.5 months). Part 2 (dose expansion): predose (0h) and 1,2,3,6h postdose on D16 of C1; predose (0h) on D3, D17 of C1; study completion (up to 55.5 months). Part 3: 3h postdose on D1 of C1; 1,2,3,4,8h postdose on D15 of C1; Predose (0h) on D1 of C1, C2-6, C≥7, D15 of C1 (cycle length=28 days; up to 54.5 months)
Measured: Parts 1 and 2: D1,D3,D16,D17 of C1; study completion. Part 2: D3,D16, D17 of C1; study completion. Part 3: D15 of C1; D1 of C1 to C6, C≥7 (cycle length=28 days; up to 54.5 months) [detailed timeframe is provided in endpoint description]
Cmax of Paclitaxel
Parts 1 and 2 (dose escalation): pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 2,4,6,24 h post-paclitaxel infusion on D2 and D16 of C1; study completion (up to 55.5 months). Part 2 (dose expansion): pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 1,2,3,6,24 h post-paclitaxel infusion on D1 of C1; pre-paclitaxel infusion (0 h), end of paclitaxel infusion (infusion length = 60 minutes), end of bevacizumab infusion (infusion length = 30 to 90 minutes), 2, 4, 6, 24 h post-paclitaxel infusion on D16 of C1; study completion (cycle length=28 days; up to 55.5 months)
Measured: Parts 1 and 2 (dose escalation): D2 and D16 of C1; study completion. Part 2 (dose expansion): D1 and D16 of C1; study completion (cycle length=28 days; up to 55.5 months) [detailed timeframe is provided in endpoint description]
Cmax of Letrozole
Measured: Part 3: 1,2,3,4,8h postdose on D15 of C1; Predose (0h) on D1 of C1, C2-6, C≥7, D15 of C1 (cycle length=28 days; up to 54.5 months)
Percentage of Participants With Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)
Measured: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])
Duration of Response According to Modified RECIST
Measured: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])
Percentage of Participants With Death or Disease Progression According to Modified RECIST
Measured: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])
Progression-free Survival According to Modified RECIST
Measured: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2009Dec 2015

First posted18 Aug 2009 (estimated)
Study startAug 2009
Primary completionDec 2015
Study completionDec 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by Genentech, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 71 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00960960
Sponsor's protocol ID: GDC4629g
Other IDs: GO01304, 2009-010781-38, 2009
Status last verified: Dec 2016
First submitted: 13 Aug 2009
Last updated: 15 Dec 2016
Results posted: No

Publications

Schoffski P, Cresta S, Mayer IA, Wildiers H, Damian S, Gendreau S, Rooney I, Morrissey KM, Spoerke JM, Ng VW, Singel SM, Winer E. A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with letrozole in advanced breast cancer. Breast Cancer Res. 2018 Sep 5;20(1):109. doi: 10.1186/s13058-018-1015-x.
PubMed 30185228

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of PI3-Kinase Inhibitor GDC-0941 (Pictilisib) in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, and With Letrozole in Patients With Locally Recurrent Or Metastatic Breast Cancer
ClinicalTrials.gov ID: NCT00960960
Acronym / sponsor ID: GDC4629g
Conditions: Breast Cancer
Keywords: MBC, PI3K, Avastin, Herceptin
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 71 participants (actual)
Lead sponsor: Genentech, Inc.Industry (pharma, biotech, devices)
Study start: Aug 2009
Primary completion: Dec 2015 (actual)
Study completion: Dec 2015 (actual)
First posted: 18 Aug 2009 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 11

Arm	Type	Receives
Part 1 (Cohort 1-2): Pictilisib 60 mg +Paclitaxel +Bevacizumab	Experimental	Drug: Bevacizumab, Drug: Pictilisib, Drug: PaclitaxelPictilisib 60 mg will be administered orally (PO) once daily (QD) for 21 consecutive days of each 28-day cycle (21+7 schedule) with paclitaxel 90 milligrams per meter square (mg/m^2) intravenously (IV) on Days 1, 8, and 15 and bevacizumab 10 milligrams per kilogram (mg/kg) IV on Days 1 and 15 of each 28-day cycle. In Cohort 1 (Part 1), pictilisib will be evaluated with paclitaxel only; participants in Cohort 1 (Part 1) will be eligible to receive bevacizumab starting at Cycle 2. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.
Part 1 (Cohort 3): Pictilisib 100 mg+ Paclitaxel + Bevacizumab	Experimental	Drug: Bevacizumab, Drug: Pictilisib, Drug: PaclitaxelPictilisib 100 mg will be administered PO QD for 21 consecutive days of each 28-day cycle (21+7 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.
Part 2 (Arm A: Cohort 1a): Pictilisib 165 mg + Paclitaxel	Experimental	Drug: Pictilisib, Drug: PaclitaxelPictilisib 165 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity
Part 2 (Arm A: Cohort 2a): Pictilisib 250 mg + Paclitaxel	Experimental	Drug: Pictilisib, Drug: PaclitaxelPictilisib 250 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.
Part 2 (Arm A: Cohort 3a): Pictilisib 330 mg + Paclitaxel	Experimental	Drug: Pictilisib, Drug: PaclitaxelPictilisib 330 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.
Part2(Arm B:Cohort 1b):Pictilisib 200mg+Paclitaxel+Bevacizumab	Experimental	Drug: Bevacizumab, Drug: Pictilisib, Drug: PaclitaxelPictilisib 200 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.
Part2(Arm B:Cohort 2b):Pictilisib 250mg+Paclitaxel+Bevacizumab	Experimental	Drug: Bevacizumab, Drug: Pictilisib, Drug: PaclitaxelPictilisib 250 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.
Part2(Arm B:Cohort 3b):Pictilisib 260mg+Paclitaxel+Bevacizumab	Experimental	Drug: Bevacizumab, Drug: Pictilisib, Drug: PaclitaxelPictilisib 260 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and bevacizumab 10 mg/kg IV on Days 1 and 15 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.
Part2(Arm C:Cohort 1c):Pictilisib 180mg+Paclitaxel+Trastuzumab	Experimental	Drug: Pictilisib, Drug: Paclitaxel, Drug: TrastuzumabPictilisib 180 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and trastuzumab 2-4 mg/kg IV on Days 1, 8, 15, and 22 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.
Part2(Arm C:Cohort 2c):Pictilisib 260mg+Paclitaxel+Trastuzumab	Experimental	Drug: Pictilisib, Drug: Paclitaxel, Drug: TrastuzumabPictilisib 260 mg will be administered PO QD for repeated rounds of 5 consecutive days followed by 2 consecutive drug-free days in each 28-day cycle (5+2 schedule) with paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 and trastuzumab 2-4 mg/kg IV on Days 1, 8, 15, and 22 of each 28-day cycle. Cycle 1 will be 29 days and subsequent cycles will be 28 days. Study treatment will continue until disease progression or unacceptable toxicity.
Part 3: Pictilisib 260 mg + Letrozole	Experimental	Drug: Pictilisib, Drug: LetrozolePictilisib 260 mg will be administered PO QD continuously with letrozole 2.5 mg PO QD for each 28-day cycle. Study treatment will continue until disease progression or unacceptable toxicity.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease
Adequate organ and bone marrow function as assessed by laboratory tests
Evaluable disease or disease measurable per RECIST
Agreement to use an effective form of contraception for the duration of the study

Key exclusion criteria (13 listed)

History of malabsorption syndrome or other condition that would interfere with enteral absorption
Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytic agents
Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, radiotherapy, or hormonal therapy) within 4 weeks or 5 half-lives (whichever is shorter) of the first dose of study treatment
Uncontrolled current illness
Active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BevacizumabAlso: AvastinBevacizumab will be administered IV at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle.	Drug	Part 1 (Cohort 1-2): Pictilisib 60 mg +Paclitaxel +Bevacizumab, Part 1 (Cohort 3): Pictilisib 100 mg+ Paclitaxel + Bevacizumab, Part2(Arm B:Cohort 1b):Pictilisib 200mg+Paclitaxel+Bevacizumab, Part2(Arm B:Cohort 2b):Pictilisib 250mg+Paclitaxel+Bevacizumab, Part2(Arm B:Cohort 3b):Pictilisib 260mg+Paclitaxel+Bevacizumab
PictilisibAlso: GDC-0941Pictilisib will be administered PO QD on escalating doses.	Drug	Part 1 (Cohort 1-2): Pictilisib 60 mg +Paclitaxel +Bevacizumab, Part 1 (Cohort 3): Pictilisib 100 mg+ Paclitaxel + Bevacizumab, Part 2 (Arm A: Cohort 1a): Pictilisib 165 mg + Paclitaxel, Part 2 (Arm A: Cohort 2a): Pictilisib 250 mg + Paclitaxel, Part 2 (Arm A: Cohort 3a): Pictilisib 330 mg + Paclitaxel, Part 3: Pictilisib 260 mg + Letrozole, Part2(Arm B:Cohort 1b):Pictilisib 200mg+Paclitaxel+Bevacizumab, Part2(Arm B:Cohort 2b):Pictilisib 250mg+Paclitaxel+Bevacizumab, Part2(Arm B:Cohort 3b):Pictilisib 260mg+Paclitaxel+Bevacizumab, Part2(Arm C:Cohort 1c):Pictilisib 180mg+Paclitaxel+Trastuzumab, Part2(Arm C:Cohort 2c):Pictilisib 260mg+Paclitaxel+Trastuzumab
LetrozoleLetrozole will be administered PO at a dose of 2.5 mg QD for for each 28-day cycle.	Drug	Part 3: Pictilisib 260 mg + Letrozole
PaclitaxelPaclitaxel will be administered IV at a dose of 90 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle.	Drug	Part 1 (Cohort 1-2): Pictilisib 60 mg +Paclitaxel +Bevacizumab, Part 1 (Cohort 3): Pictilisib 100 mg+ Paclitaxel + Bevacizumab, Part 2 (Arm A: Cohort 1a): Pictilisib 165 mg + Paclitaxel, Part 2 (Arm A: Cohort 2a): Pictilisib 250 mg + Paclitaxel, Part 2 (Arm A: Cohort 3a): Pictilisib 330 mg + Paclitaxel, Part2(Arm B:Cohort 1b):Pictilisib 200mg+Paclitaxel+Bevacizumab, Part2(Arm B:Cohort 2b):Pictilisib 250mg+Paclitaxel+Bevacizumab, Part2(Arm B:Cohort 3b):Pictilisib 260mg+Paclitaxel+Bevacizumab, Part2(Arm C:Cohort 1c):Pictilisib 180mg+Paclitaxel+Trastuzumab, Part2(Arm C:Cohort 2c):Pictilisib 260mg+Paclitaxel+Trastuzumab
TrastuzumabAlso: HerceptinTrastuzumab will be administered IV at a dose of 2-4 mg/kg on on Days 1, 8, 15, and 22 of each 28-day cycle.	Drug	Part2(Arm C:Cohort 1c):Pictilisib 180mg+Paclitaxel+Trastuzumab, Part2(Arm C:Cohort 2c):Pictilisib 260mg+Paclitaxel+Trastuzumab

Primary outcome

Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: First treatment cycle (Day 1 up to Day 29)
Maximum Tolerated Dose (MTD) of Pictilisib
Time frame: First treatment cycle (Day 1 up to Day 29)
Recommended Phase II Dose (RP2D) of Pictilisib
Time frame: Baseline up to 54.2 months
Number of Cycles of Each Component of the Treatment Regimen
Time frame: Baseline up to 54.2 months
Dose Intensity of Each Component of the Treatment Regimen
Time frame: Baseline up to 54.2 months

13 secondary outcomes

Minimum Observed Plasma Concentration (Cmin) of Pictilisib
Time frame: Parts 1 and 2 (dose escalation): predose (0 hours [h]) on Day (D) 1,3,16, and 17 of Cycle (C) 1. Part 2 (dose expansion): predose (0h) on D3,16,17 of C1; Part 3: Predose (0h) on D1 of C1, C2-6, C≥7, D15 of C1 (cycle length=28 days; up to 54.5 months)
Cmin of Paclitaxel
Time frame: Parts 1 and 2 (dose escalation): pre-paclitaxel infusion (0 h) on D2 and D16 of C1. Part 2 (dose expansion): pre-paclitaxel infusion (0 h) on D1 and D16 of C1 (cycle length=28 days)
Cmin of Letrozole
Time frame: Part 3: Predose (0h) on D1 of C1, C2-6, C≥7, D15 of C1 (cycle length=28 days; up to 54.5 months)
Area Under the Curve From Time Zero to Last Measurable Concentrations (AUClast) of Pictilisib
Time frame: Parts 1 and 2: D1,D3,D16,D17 of C1; study completion. Part 2: D3,D16, D17 of C1; study completion. Part 3: D15 of C1; D1 of C1 to C6, C≥7 (cycle length=28 days; up to 54.5 months) [detailed timeframe is provided in endpoint description]
AUClast of Paclitaxel
Time frame: Parts 1 and 2 (dose escalation): D2 and D16 of C1; study completion. Part 2 (dose expansion): D1 and D16 of C1; study completion (cycle length=28 days; up to 55.5 months) [detailed timeframe is provided in endpoint description]
AUClast of Letrozole
Time frame: Part 3: 1,2,3,4,8h postdose on D15 of C1; Predose (0h) on D1 of C1, C2-6, C≥7, D15 of C1 (cycle length=28 days; up to 54.5 months)
Maximum Observed Plasma Concentration (Cmax) of Pictilisib
Time frame: Parts 1 and 2: D1,D3,D16,D17 of C1; study completion. Part 2: D3,D16, D17 of C1; study completion. Part 3: D15 of C1; D1 of C1 to C6, C≥7 (cycle length=28 days; up to 54.5 months) [detailed timeframe is provided in endpoint description]
Cmax of Paclitaxel
Time frame: Parts 1 and 2 (dose escalation): D2 and D16 of C1; study completion. Part 2 (dose expansion): D1 and D16 of C1; study completion (cycle length=28 days; up to 55.5 months) [detailed timeframe is provided in endpoint description]
Cmax of Letrozole
Time frame: Part 3: 1,2,3,4,8h postdose on D15 of C1; Predose (0h) on D1 of C1, C2-6, C≥7, D15 of C1 (cycle length=28 days; up to 54.5 months)
Percentage of Participants With Objective Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])
Duration of Response According to Modified RECIST
Time frame: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])
Percentage of Participants With Death or Disease Progression According to Modified RECIST
Time frame: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])
Progression-free Survival According to Modified RECIST
Time frame: Screening up to disease progression or death up to approximately 55.5 months (assessed at Screening and at the end [Days 22-28] of Cycles 2, 5, 8, and 11 and every 3 cycles thereafter [cycle length=28 days; up to approximately 55.5 months])

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2016.
Derived from this study: PubMed 30185228Schoffski P, Cresta S, Mayer IA, Wildiers H, Damian S, Gendreau S, Rooney I, Morrissey KM, Spoerke JM, Ng VW, Singel SM, Winer E. A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with letrozole in advanced breast cancer. Breast Cancer Res. 2018 Sep 5;20(1):109. doi: 10.1186/s13058-018-1015-x.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stina Singel, M.D., Ph.D. study director

Genentech, Inc.

5 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bevacizumab, Pictilisib and Letrozole in people with Breast Cancer, run by Genentech, Inc. at 5 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Belgium, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Dose-Limiting Toxicities (DLTs) (time frame: First treatment cycle (Day 1 up to Day 29)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00960960, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2016.