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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01437566




Registration number
NCT01437566
Ethics application status
Date submitted
8/09/2011
Date registered
21/09/2011
Date last updated
2/11/2016

Titles & IDs
Public title
Study of GDC-0941 or GDC-0980 With Fulvestrant Versus Fulvestrant in Advanced or Metastatic Breast Cancer in Participants Resistant to Aromatase Inhibitor Therapy
Scientific title
A Phase II, Double-Blind, Placebo Controlled, Randomized Study of GDC-0941 or GDC-0980 With Fulvestrant Versus Fulvestrant in Advanced or Metastatic Breast Cancer in Patients Resistant to Aromatase Inhibitor Therapy
Secondary ID [1] 0 0
GO00769
Secondary ID [2] 0 0
GDC4950g
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 - Fulvestrant
Treatment: Drugs - GDC-0941
Treatment: Drugs - GDC-0941 Matching Placebo
Treatment: Drugs - GDC-0980
Treatment: Drugs - GDC-0980 Matching Placebo

Placebo Comparator: GDC-0941 Matching Placebo + Fulvestrant (Arm E) - Participants with PIK3CA mutation will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle and GDC-0941 matching placebo QD orally starting on Day 1 of Cycle 1, each cycle of 28 days. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.

Experimental: GDC-0941-260 mg + Fulvestrant (Arm D) - Participants with PIK3CA mutation will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle and GDC-0941 260 mg QD orally starting on Day 1 of Cycle 1, each cycle of 28 days. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.

Experimental: GDC-0941-340 mg + Fulvestrant (Arm A) - Participants will receive fulvestrant 500 milligrams (mg) as 2 intramuscular (IM) injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle and GDC-0941 340 mg once daily (QD) orally starting on Day 15 of Cycle 1, each cycle of 28 days. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.

Placebo Comparator: GDC-0948 or GDC-0980 Matching Placebo + Fulvestrant (Arm C) - Participants will be randomized in 1:1 ratio to receive GDC-0948 matching placebo or GDC-0980 matching placebo with fulvestrant. Participants will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle and GDC-0948 or GDC-0980 matching placebo QD orally starting on Day 15 of Cycle 1, each cycle of 28 days. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.

Experimental: GDC-0980-30 mg + Fulvestrant (Arm B) - Participants will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle and GDC-0980 30 mg QD orally starting on Day 15 of Cycle 1, each cycle of 28 days. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.


Treatment: Drugs: Fulvestrant
Participants will receive fulvestrant 500 mg as 2 IM injections of 250 mg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent cycle, each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.

Treatment: Drugs: GDC-0941
Participants will receive GDC-0941 260 mg (Part II) or 340 mg (Part I) QD orally from Day 1 or Day 15 of Cycle 1 until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.

Treatment: Drugs: GDC-0941 Matching Placebo
Participants will receive GDC-0941 matching placebo QD orally from Day 1 or Day 15 of Cycle 1 until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.

Treatment: Drugs: GDC-0980
Participants will receive GDC-0980 30 mg (Part I) QD orally from Day 15 of Cycle 1 until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.

Treatment: Drugs: GDC-0980 Matching Placebo
Participants will receive GDC-0980 matching placebo QD orally from Day 15 of Cycle 1 until disease progression, intolerable toxicity, elective withdrawal from the study, study completion or termination.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival as Assessed by the Investigator Per modified RECIST v 1.1
Timepoint [1] 0 0
From Screening to up to approximately 5 years (assessed at Screening, after 8, 16, 24 and 32 weeks of treatment, every 12 weeks thereafter until disease progression or initiation of other anti-cancer therapy)
Primary outcome [2] 0 0
Percentage of Participants with Adverse Events
Timepoint [2] 0 0
Baseline to up to 30 days after the last dose of study drug (Approximately 5 years)
Secondary outcome [1] 0 0
Percentage of Participants with Objective Tumor Response (Complete Response [CR] or Partial Response [PR] as Assessed by the Investigator Per Modified RECIST v 1.1
Timepoint [1] 0 0
From Screening to up to approximately 5 years (assessed at Screening, after 8, 16, 24 and 32 weeks of treatment, every 12 weeks thereafter until disease progression or initiation of other anti-cancer therapy)
Secondary outcome [2] 0 0
Percentage of Participants with Clinical Benefit Response Defined as PR, CR, or SD Per Modified RECIST v 1.1
Timepoint [2] 0 0
From Screening to up to approximately 5 years (assessed at Screening, after 8, 16, 24 and 32 weeks of treatment, every 12 weeks thereafter until disease progression or initiation of other anti-cancer therapy)
Secondary outcome [3] 0 0
Duration of Confirmed Objective Response as Assessed by the investigator Per Modified RECIST v 1.1
Timepoint [3] 0 0
From Screening to up to approximately 5 years (assessed at Screening, after 8, 16, 24 and 32 weeks of treatment, every 12 weeks thereafter until disease progression or initiation of other anti-cancer therapy)
Secondary outcome [4] 0 0
Percentage of Participants with PIK3CA Mutant Tumors
Timepoint [4] 0 0
Baseline
Secondary outcome [5] 0 0
Time to Maximum Plasma Concentration (Tmax) of GDC-0941 and GDC-0948
Timepoint [5] 0 0
Part 1:0-4 hour (hr) predose (PrD), 1,2,4 hr postdose (PoD) on Day 15 of Cycles 1 & 2, PrD on Cycle 1 Day 16, 0-4 hr PrD & 2 hr PoD on Cycle 6 Day 1; Part II:0-4 hr PrD, 2 hr PoD on Day 1 of Cycles 1 & 6, 0-4 hr PrD, 1, 2, 4 hr PoD on Cycle 2 Day 1
Secondary outcome [6] 0 0
Maximum Plasma Concentration (Cmax) of GDC-0941 and GDC-0948
Timepoint [6] 0 0
Part 1:0-4 hr PrD, 1,2,4 hr PoD on Day 15 of Cycles 1 & 2, PrD on Cycle 1 Day 16, 0-4 hr PrD & 2 hr PoD on Cycle 6 Day 1; Part II:0-4 hr PrD, 2 hr PoD on Day 1 of Cycles 1 & 6, 0-4 hr PrD, 1, 2, 4 hr PoD on Cycle 2 Day 1
Secondary outcome [7] 0 0
Area Under the Concentration Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of GDC-0941 and GDC-0948
Timepoint [7] 0 0
Part 1:0-4 hr PrD, 1,2,4 hr PoD on Day 15 of Cycles 1 & 2, PrD on Cycle 1 Day 16, 0-4 hr PrD & 2 hr PoD on Cycle 6 Day 1; Part II:0-4 hr PrD, 2 hr PoD on Day 1 of Cycles 1 & 6, 0-4 hr PrD, 1, 2, 4 hr PoD on Cycle 2 Day 1

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

- As per national or local treatment guidelines, endocrine therapy (i.e., fulvestrant)
is recommended and treatment with cytotoxic chemotherapy is not necessary for
participants, at time of entry into the study.

- Part I: Postmenopausal women with locally ABC or MBC whose disease relapsed during
treatment with (or within 6 months after discontinuation of) an AI in the adjuvant
setting or progressed during treatment with an AI in the metastatic setting.

- Part II: Postmenopausal women with locally ABC or MBC whose disease has progressed
during or after treatment with an AI. Participants who discontinued the AI for
toxicity rather than completion of regimen or for disease progression are not eligible

- Estrogen receptor (ER)-positive disease and human epidermal receptor 2 (HER2)-negative
disease

- Participants must have measurable disease by response evaluation criteria in solid
tumors (RECIST) version (v) 1.1 or bone-only disease with radiologic scans

- Adequate hematologic and end-organ function
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior treatment with fulvestrant, phosphoinositide 3-kinase (PI3K) inhibitor, or
mechanistic target of rapamycin (mTOR) inhibitor for ABC or MBC

- Prior anti-cancer therapy or radiotherapy within 2 weeks prior to Day 1 of Cycle 1

- Prior treatment with greater than (>) one cytotoxic chemotherapy regimens or
experienced recurrent or progressive disease on > two endocrine therapies for MBC

- Participants requiring anti-hyperglycemic therapy

- Clinically significant cardiac or pulmonary dysfunction

- History of malabsorption syndrome or other condition that would interfere with enteral
absorption

- Clinically significant history of liver disease

- Active uncontrolled autoimmune disease or active inflammatory disease

- Immunocompromised status

- Need for current chronic corticosteroid therapy

- Pregnancy, lactation, or breastfeeding

- Current severe, uncontrolled systemic disease

- Symptomatic hypercalcemia

- Known untreated or active central nervous system (CNS) metastases

- History of other malignancy within the previous 5 years, except for appropriately
treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine
cancer, or patients who have undergone potentially curative therapy with no evidence
of disease and are deemed by the treating physician to be at low risk for recurrence

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2016
Sample size
Target
Accrual to date
Final
318
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
- Kogarah
Recruitment hospital [2] 0 0
- Wahroonga
Recruitment hospital [3] 0 0
- South Brisbane
Recruitment hospital [4] 0 0
- Bedford Park
Recruitment hospital [5] 0 0
- Woodville
Recruitment hospital [6] 0 0
- Frankston
Recruitment hospital [7] 0 0
- Parkville
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2076 - Wahroonga
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5042 - Bedford Park
Recruitment postcode(s) [5] 0 0
5011 - Woodville
Recruitment postcode(s) [6] 0 0
3199 - Frankston
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment outside Australia
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United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
California
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United States of America
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District of Columbia
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Florida
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Georgia
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Illinois
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Kansas
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Massachusetts
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Missouri
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New Jersey
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New York
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Virginia
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Argentina
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Buenos Aires
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Argentina
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Santa Fe
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Belgium
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Bruxelles
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Belgium
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Edegem
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Leuven
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Liège
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Quebec
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Santiago
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Temuco
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Valparaiso
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Chile
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Vina del Mar
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Brno
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Olomouc
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Praha 2
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Herlev
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Roskilde
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Århus
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France
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Paris
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Trier
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Pokfulam
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Israel
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Holon
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Israel
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Rehovot
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Umbria
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Korea, Republic of
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Malaysia
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Kuala Lumpur
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Penang
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Malaysia
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Mexico
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León
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New Zealand
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Christchurch
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New Zealand
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Hamilton
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New Zealand
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Wellington
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Peru
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Lima
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Russian Federation
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Chelyabinsk
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Russian Federation
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Kazan
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Moscow
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Russian Federation
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Voronezh
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Singapore
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Singapore
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Spain
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Barcelona
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Spain
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Lerida
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Spain
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Valencia
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Spain
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Zaragoza
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Thailand
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Patumwan
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Thailand
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Songkhla
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United Kingdom
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Brighton
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United Kingdom
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Cardiff
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United Kingdom
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London
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United Kingdom
State/province [84] 0 0
Stoke on Trent

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicenter, international, randomized, double-blinded, placebo-controlled, Phase
II trial. Participants with advanced breast cancer (ABC) or Metastatic Breast Cancer (MBC)
who have experienced recurrence or progression of their disease while receiving aromatase
inhibitor (AI) therapy or who have relapsed within 6 months after completing adjuvant AI
therapy will be enrolled in Part I of this study. Participants with ABC or MBC who have
received prior AI therapy and who have PIK3CA-mutant tumors will be enrolled in Part II of
this study. Part I of the study will assess the effect of the addition of GDC-0941 to
fulvestrant (Arm A) and of GDC-0980 to fulvestrant (Arm B) on progression free survival (PFS)
compared with fulvestrant + placebo (Arm C). Part II of the study will examine the safety and
tolerability and to estimate the effect of GDC-0941 in combination with fulvestrant (Arm D)
on PFS versus fulvestrant + placebo (Arm E) in participants who received prior treatment with
an AI and whose tumors contain a PIK3CA mutation.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01437566
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gallia Levy, M.D., Ph.D.
Address 0 0
Genentech, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01437566