- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01042379
I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (I-SPY)
I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
Study Overview
Status
Conditions
Intervention / Treatment
- Drug: Standard Therapy
- Drug: AMG 386 with or without Trastuzumab
- Drug: AMG 386 and Trastuzumab
- Drug: AMG 479 (Ganitumab) plus Metformin
- Drug: MK-2206 with or without Trastuzumab
- Drug: T-DM1 and Pertuzumab
- Drug: Pertuzumab and Trastuzumab
- Drug: Ganetespib
- Drug: ABT-888
- Drug: Neratinib
- Drug: PLX3397
- Drug: Pembrolizumab - 4 cycle
- Drug: Talazoparib plus Irinotecan
- Drug: Patritumab and Trastuzumab
- Drug: Pembrolizumab - 8 cycle
- Drug: SGN-LIV1A
- Drug: Durvalumab plus Olaparib
- Drug: SD-101 + Pembrolizumab
- Drug: Tucatinib plus trastuzumab and pertuzumab
- Drug: Cemiplimab
- Drug: Cemiplimab plus REGN3767
- Drug: Trilaciclib with or without trastuzumab + pertuzumab
- Drug: SYD985 ([vic-]trastuzumab duocarmazine)
- Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
- Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab
- Drug: Amcenestrant
- Drug: Amcenestrant + Abemaciclib
- Drug: Amcenestrant + Letrozole
- Drug: ARX788
- Drug: ARX788 + Cemiplimab
- Drug: VV1 + Cemiplimab
- Drug: Datopotamab deruxtecan
- Drug: Datopotamab deruxtecan + Durvalumab
- Drug: Zanidatamab
- Drug: Lasofoxifene
- Drug: Z-endoxifen
- Drug: ARV-471
- Drug: ARV-471 + Letrozole
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Won Chang
- Phone Number: (855) 866-0505
- Email: w.chang@quantumleaphealth.org
Study Contact Backup
- Name: Maria Pitsiouni, PhD
- Email: m.pitsiouni@quantumleaphealth.org
Study Locations
-
-
Alabama
-
Birmingham, Alabama, United States, 35294
- Recruiting
- University of Alabama at Birmingham
-
Principal Investigator:
- Erica Stringer-Reasor, MD
-
-
Arizona
-
Scottsdale, Arizona, United States, 85259
- Not yet recruiting
- Mayo Clinic - Scottsdale
-
Contact:
- Phone Number: 507-538-7623
-
Principal Investigator:
- Donald Northfelt, MD
-
Tucson, Arizona, United States, 85724
- Active, not recruiting
- University of Arizona
-
-
California
-
Duarte, California, United States, 91010
- Recruiting
- City of Hope
-
Contact:
- Phone Number: 800-826-4673
-
Principal Investigator:
- Jennifer Tseng, MD
-
La Jolla, California, United States, 92093-0698
- Recruiting
- University of California San Diego
-
Contact:
- Phone Number: 858-822-6194
-
Contact:
- Phone Number: 858-822-6194
- Email: CancerCTO@ucsd.edu
-
Principal Investigator:
- Anne Wallace, MD
-
Los Angeles, California, United States, 90033
- Recruiting
- University of Southern California
-
Contact:
- Kristy Watkins, RN
- Phone Number: 323-865-0452
- Email: Watkins_K@ccnt.usc.edu
-
Principal Investigator:
- Evanthia Roussos Torres, MD
-
Newport Beach, California, United States, 92663
- Recruiting
- Hoag Memorial Hospital Presbyterian
-
Principal Investigator:
- Chaitali Nangia, MD
-
San Francisco, California, United States, 94115
- Recruiting
- University of California San Francisco (UCSF)
-
Contact:
- Phone Number: 415-443-4296
-
Principal Investigator:
- Amy Jo Chien, MD
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- Recruiting
- University of Colorado
-
Contact:
- Phone Number: 720-848-1622
-
Principal Investigator:
- Anthony Elias, MD
-
-
Connecticut
-
New Haven, Connecticut, United States, 06510
- Recruiting
- Yale Cancer Center
-
Contact:
- Trisha Burello, MS
- Phone Number: 203-737-2848
- Email: trisha.burrello@yale.edu
-
Sub-Investigator:
- Tara Snaft, MD
-
Sub-Investigator:
- Lajos Pusztai, MD
-
Principal Investigator:
- Marlya Rozenblit, MD
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20007
- Recruiting
- Georgetown University Medical Center
-
Contact:
- Minetta Liu, MD
- Phone Number: 202-444-3677
- Email: Liumc@georgetown.edu
-
Principal Investigator:
- Claudine Isaacs, MD
-
-
Florida
-
Tampa, Florida, United States, 33612
- Recruiting
- Moffitt Cancer Center
-
Principal Investigator:
- Heather Han, MD
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Recruiting
- Winship Cancer Institute of Emory University
-
Principal Investigator:
- Kevin Kalinsky, MD
-
-
Illinois
-
Chicago, Illinois, United States, 60453
- Recruiting
- University of Chicago
-
Contact:
- Phone Number: 773-834-2756
-
Principal Investigator:
- Rita Nanda, MD
-
Maywood, Illinois, United States, 60153
- Recruiting
- Loyola University
-
Contact:
- Phone Number: 708-327-3102
-
Principal Investigator:
- Kathy S Albain, MD
-
-
Kansas
-
Westwood, Kansas, United States, 66205
- Active, not recruiting
- University of Kansas
-
-
Michigan
-
Lansing, Michigan, United States, 48912
- Recruiting
- Herbert-Herman Cancer Center, Sparrow Hospital
-
Principal Investigator:
- Brittani Thomas, DO
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55455
- Recruiting
- University of Minnesota
-
Contact:
- Phone Number: 612-626-8487
-
Principal Investigator:
- Douglas Yee, MD
-
Rochester, Minnesota, United States, 55905
- Recruiting
- Mayo Clinic
-
Contact:
- Phone Number: 507-538-7623
-
Principal Investigator:
- Judy C Boughey, MD
-
-
New Jersey
-
New Brunswick, New Jersey, United States, 08903
- Recruiting
- Rutgers Cancer Institute of New Jersey
-
Contact:
- Phone Number: 732-235-7356
-
Principal Investigator:
- Coral Omene, MD, PhD
-
-
New York
-
Bronx, New York, United States, 10467
- Not yet recruiting
- Montefiore Medical Center
-
Principal Investigator:
- Jesus D Anampa
-
New York, New York, United States, 10032
- Recruiting
- Columbia University Medical Center
-
Principal Investigator:
- Meghana Trivedi, MD
-
Rochester, New York, United States, 14642
- Recruiting
- University of Rochester Wilmot Cancer Institute
-
Contact:
-
Principal Investigator:
- Carla Folksm, MD
-
-
North Carolina
-
Winston-Salem, North Carolina, United States, 27157
- Recruiting
- Wake Forest Baptist Comprehensive Cancer Center
-
Contact:
- Angela Howell, MD
- Phone Number: 336-716-5440
- Email: anhowell@wakehealth.edu
-
Principal Investigator:
- Alexandra Thomas, MD
-
-
Ohio
-
Cleveland, Ohio, United States, 44106
- Recruiting
- Cleveland Clinic
-
Principal Investigator:
- Julie Lang, MD
-
Contact:
- Phone Number: 800-233-2273
-
-
Oregon
-
Portland, Oregon, United States, 97239
- Recruiting
- Oregon Health & Science Institute (OHSU)
-
Contact:
- Taylor Knapp
- Phone Number: 503-494-4438
- Email: knappt@ohsu.edu
-
Contact:
- Phone Number: 503-494-8573
-
Principal Investigator:
- Alexandra Zimmer, MD
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- Recruiting
- University of Pennsylvania (U Penn)
-
Contact:
- Phone Number: 215-614-1850
-
Principal Investigator:
- Amy Clark, MD
-
Pittsburgh, Pennsylvania, United States, 15213
- Active, not recruiting
- University Pittsburgh Medical Center
-
-
South Dakota
-
Sioux Falls, South Dakota, United States, 57104
- Recruiting
- Sanford Clinical Research
-
Principal Investigator:
- Amy Sanford, MD
-
-
Tennessee
-
Nashville, Tennessee, United States, 27204
- Recruiting
- Vanderbilt University Medical Center
-
Principal Investigator:
- Laura Kennedy, MD
-
-
Texas
-
Dallas, Texas, United States, 75390-9155
- Active, not recruiting
- University of Texas, Southwestern Medical Center
-
Houston, Texas, United States, 77230-1439
- Active, not recruiting
- University of Texas, M.D. Anderson Cancer Center
-
-
Virginia
-
Falls Church, Virginia, United States, 22042
- Active, not recruiting
- Inova Health System
-
-
Washington
-
Seattle, Washington, United States, 98104
- Active, not recruiting
- Swedish Cancer Institute
-
Seattle, Washington, United States, 98115
- Active, not recruiting
- University of Washington
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologically confirmed invasive cancer of the breast
- Clinically or radiologically measureable disease in the breast after diagnostic biopsy, defined as longest diameter greater than or equal to 25 mm (2.5cm)
- No prior cytotoxic regimens are allowed for this malignancy. Patients may not have had prior chemotherapy or prior radiation therapy to the ipsilateral breast for this malignancy. Prior bis-phosphonate therapy is allowed
- Age ≥18 years
- ECOG performance status 0-1
- Willing to undergo core biopsy of the primary breast lesion to assess baseline biomarkers
- Non-pregnant and non-lactating
- No ferromagnetic prostheses. Patients who have metallic surgical implants that are not compatible with an MRI machine are not eligible.
- Ability to understand and willingness to sign a written informed consent (I-SPY TRIAL Screening Consent)
- Eligible tumors must meet one of the following criteria: Stage II or III, or T4, any N, M0, including clinical or pathologic inflammatory cancer or Regional Stage IV, where supraclavicular lymph nodes are the only sites metastasis
- Any tumor ER/PgR status, any HER-2/neu status as measured by local hospital pathology laboratory and meets any tumor assay profile described in protocol section 4.1.2F
- Normal organ and marrow function: Leukocytes ≥ 3000/μL, Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 100,000/μL, Total bilirubin within normal institutional limits, unless patient has Gilbert's disease, for which bilirubin must be ≤ 2.0 x ULN, AST(SGOT)/ALT (SGPT) ≤ 1.5 x institutional ULN, creatinine < 1.5 x institutional ULN
- No uncontrolled or severe cardiac disease. Baseline ejection fraction (by nuclear imaging or echocardiography) must by ≥ 50%
- No clinical or imaging evidence of distant metastases by PA and Lateral CXR, Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline phosphatase
- Tumor assay profile must include on of the following: MammaPrint High, any ER status, any HER2 status, or MammaPrint Low, ER negative (<5%), any HER2 status, or MammaPrint Low, ER positive, HER2/neu positive by any one of the three methods used (IHC, FISH, TargetPrint™)
- Ability to understand and willingness to sign a written informed consent document (I-SPY 2 TRIAL Consent #2)
Exclusion Criteria:
- Use of any other investigational agents within 30 days of starting study treatment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent or accompanying supportive medications.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Standard Therapy
Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
|
Paclitaxel: 80 mg/m2 IV during the 12 weekly treatment cycles post randomization; Doxorubicin: 60 mg/m2 IV after completion of the 12 weekly treatment cycles and prior to surgery for weeks 13-16; Cyclophosphamide: 600 mg/m2 IV after completion of the 12 weekly treatment cycles and prior to surgery for weeks 13-16
Other Names:
|
Experimental: AMG 386 with or without Trastuzumab
Arm is closed.
|
Arm is closed.
Other Names:
Arm is closed.
Other Names:
|
Other: AMG 479 plus Metformin
Arm is closed.
|
Arm is closed.
Other Names:
|
Experimental: MK-2206 with or without Trastuzumab
Arm is closed.
|
Arm is closed.
Other Names:
|
Experimental: T-DM1 and Pertuzumab
Arm is closed.
|
Arm is closed.
Other Names:
|
Active Comparator: Pertuzumab and Trastuzumab
Novel Control Investigational Agent.
Arm is closed.
|
Pertuzumab: 840 mg IV (loading dose) week 1 and 420 mg every 3 weeks (weeks 4, 7, 10) post-randomization; Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
Other Names:
|
Experimental: Ganetespib
Arm is closed.
|
Arm is closed.
|
Other: ABT-888
Arm is closed.
|
Arm is closed.
Other Names:
|
Other: Neratinib
Arm is closed.
|
Arm is closed.
|
Experimental: PLX3397
Arm is closed.
|
Arm is closed.
|
Experimental: Pembrolizumab 4 cycle
Arm is closed.
|
Arm is closed.
|
Experimental: Talazoparib plus Irinotecan
Arm is closed.
|
Arm is closed.
|
Experimental: Patritumab with or without Trastuzumab
Arm is closed.
|
Arm is closed.
|
Experimental: Pembrolizumab 8 cycle
Arm is closed.
|
Arm is closed.
|
Experimental: SGN-LIV1A
Arm is closed.
|
Arm is closed.
SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16
|
Experimental: Durvalumab plus Olaparib
Arm is closed.
|
Arm is closed.
|
Experimental: SD-101 + Pembrolizumab
Arm is closed.
|
Arm is closed.
SD-101: IT injection 2 mg/ml (1 ml for T2 tumors, 2 ml for >T3 tumors) weekly x 4, then every 3 weeks x 2 cycles 1,2,3,4,7,10 Pembrolizumab: 200mg IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
|
Experimental: Tucatinib
Arm is closed.
|
Arm is closed.
Tucatinib: 300 mg PO BID 12 weeks CLOSED Tucatinib: 250 mg PO BID 12 weeks CLOSED Tucatinib adaptive: 150mg BID days 1-28, 250mg BID days 29-84 Trastuzumab: 4 mg/kg IV (loading dose) cycle 1; 2 mg/kg (thereafter) cycles 2-12 Pertuzumab: 840 mg IV (loading dose) cycle 1; 420 mg (thereafter) cycles 4, 7 and 10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
|
Experimental: Cemiplimab
Novel Investigational Agent.
Arm is closed.
|
Cemiplimab: 350 mg q3w X 12 weeks IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
|
Experimental: Cemiplimab plus REGN3767
Novel Investigational Agent.
Arm is closed.
|
Cemiplimab: 350 mg q3w X 12 weeks IV cycles 1,4,7,10 REGN 3767: 1600 mg q3W X 12 weeks IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
|
Experimental: Trilaciclib with or without trastuzumab + pertuzumab
Novel Investigational Agent.
Arm is closed.
|
Trilaciclib: 240 mg/m2 IV weekly cycle 1-16 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles For HER2+: Pertuzumab: 840 mg IV (loading dose) week 1 and 420 mg every 3 weeks (weeks 4, 7, 10) post-randomization Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
Other Names:
|
Experimental: SYD985 ([vic-]trastuzumab duocarmazine)
Novel Investigational Agent.
Arm is closed.
|
SYD985: 1.2 mg/kg IV (q3w x 12 weeks) cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
|
Experimental: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
Novel Investigational Agent.
Arm is closed.
|
Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
For HER2+ Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Trastuzumab, 4 mg/kg cycle 1, then 2 mg/kg cycles 2-12 q1wk, IV, for wk1-12 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Carboplatin, AUC 1.5, IV, q1wk from wk1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle For HER2- Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Carboplatin, AUC 1.5, IV, q1wk from wk1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle
Other Names:
|
Experimental: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab
Novel Investigational Agent.
Arm is closed.
|
For HER2+ Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Trastuzumab, 4 mg/kg cycle 1, then 2 mg/kg cycles 2-12 q1wk, IV, for wk1-12 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle For HER2- Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle
Other Names:
|
Experimental: Endocrine Optimization Pilot: Amcenestrant Monotherapy
Novel Investigational Agent.
Arm is closed.
|
Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks
Other Names:
|
Experimental: Endocrine Optimization Pilot: Amcenestrant + Abemaciclib
Novel Investigational Agent.
Arm is closed.
|
Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Abemaciclib (Verzenio), 150mg BID, p.o., for 24 weeks
Other Names:
|
Experimental: Endocrine Optimization Pilot: Amcenestrant + Letrozole
Novel Investigational Agent.
Arm is closed.
|
Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Letrozole (Femara), 2.5mg QD, p.o., for 24 weeks
Other Names:
|
Experimental: ARX788 in Block A and followed by SOC in Block B
Novel investigational Agent followed by SOC
|
ARX788, 1.5 mg/kg Q3W, IV for 12 weeks
|
Experimental: VSV-IFNβ-NIS (VOYAGER V1™; VV1) + Cemiplimab in Block A and followed by SOC in block B
Novel investigational Agent followed by SOC
|
VV1, 3x10^9 TCID50 once (day-8), Intra-tumoral injection Cemiplimab, 350 mg Q3W, IV for 12 weeks
Other Names:
|
Experimental: Datopotamab Deruxtecan in Block A and followed by SOC in block B
Novel investigational Agent followed by SOC
|
Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks
Other Names:
|
Experimental: Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block B
Novel investigational Agent followed by SOC
|
Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks Durvalumab, 1120 mg Q3W, IV for 12 weeks
Other Names:
|
Experimental: ARX788 + Cemiplimab in Block A and followed by SOC in Block B
Novel investigational Agent followed by SOC.
Arm is closed.
|
ARX788, 1.5 mg/kg Q3W, IV for 12 weeks Cemiplimab, 350 mg Q3W, IV for 12 weeks
|
Experimental: Zanidatamab in Block A and followed by SOC in block B
Novel investigational Agent followed by SOC
|
Zanidatamab: Flat dose of 1,200mg Q2W for 12 weeks
|
Experimental: Endocrine Optimization Pilot: Lasofoxifene
Novel investigational Agent
|
Lasofoxifene: 5.0 mg QD, p.o., for 24 weeks
|
Experimental: Endocrine Optimization Pilot: (Z)-Endoxifen
Novel investigational Agent
|
Z-endoxifen: 10 mg QD, p.o., for 24 weeks
|
Experimental: Endocrine Optimization Pilot: ARV-471
Novel investigational Agent
|
ARV-471: 200 mg QD, p.o, for 24 weeks
|
Experimental: Endocrine Optimization Pilot: ARV-471 + Letrozole
Novel investigational Agent
|
ARV-471: 200 mg QD, p.o, for 24 weeks Letrozole: 2.5 mg QD, p.o, for 24 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Determine whether adding experimental agents to standard neoadjuvant medications increases the probability of pathologic complete response (pCR) over standard neoadjuvant chemotherapy for each biomarker signature established at trial entry.
Time Frame: Post surgery based on upto 36-week treatment
|
Post surgery based on upto 36-week treatment
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Establishing predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB).
Time Frame: Blood and Tissue Collection: Baseline, Post-Randomization, Pre-AC, Pre- and Post-Surgery
|
Blood and Tissue Collection: Baseline, Post-Randomization, Pre-AC, Pre- and Post-Surgery
|
To determine three- and five-year relapse-free survival (RFS) and OS among the treatment arms.
Time Frame: Three- and Five-Year Post-surgery Follow-up
|
Three- and Five-Year Post-surgery Follow-up
|
To determine incidence of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested.
Time Frame: Post-Randomization, Pre-AC, Pre-Surgery, Post-Surgery upto One Year during follow-up
|
Post-Randomization, Pre-AC, Pre-Surgery, Post-Surgery upto One Year during follow-up
|
MRI Volume
Time Frame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery
|
Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery
|
Collaborators and Investigators
Investigators
- Principal Investigator: Laura Esserman, MD, MBA, University of California, San Francisco
Publications and helpful links
General Publications
- Barker AD, Sigman CC, Kelloff GJ, Hylton NM, Berry DA, Esserman LJ. I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther. 2009 Jul;86(1):97-100. doi: 10.1038/clpt.2009.68. Epub 2009 May 13.
- Esserman LJ, Woodcock J. Accelerating identification and regulatory approval of investigational cancer drugs. JAMA. 2011 Dec 21;306(23):2608-9. doi: 10.1001/jama.2011.1837. No abstract available.
- Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, Hudis C, Gray JW, Perou C, Yau C, Livasy C, Krontiras H, Montgomery L, Tripathy D, Lehman C, Liu MC, Olopade OI, Rugo HS, Carpenter JT, Dressler L, Chhieng D, Singh B, Mies C, Rabban J, Chen YY, Giri D, van 't Veer L, Hylton N. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012 Sep 10;30(26):3242-9. doi: 10.1200/JCO.2011.39.2779. Epub 2012 May 29.
- Hylton NM, Blume JD, Bernreuter WK, Pisano ED, Rosen MA, Morris EA, Weatherall PT, Lehman CD, Newstead GM, Polin S, Marques HS, Esserman LJ, Schnall MD; ACRIN 6657 Trial Team and I-SPY 1 TRIAL Investigators. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL. Radiology. 2012 Jun;263(3):663-72. doi: 10.1148/radiol.12110748.
- Lin C, Buxton MB, Moore D, Krontiras H, Carey L, DeMichele A, Montgomery L, Tripathy D, Lehman C, Liu M, Olapade O, Yau C, Berry D, Esserman LJ; I-SPY TRIAL Investigators. Locally advanced breast cancers are more likely to present as Interval Cancers: results from the I-SPY 1 TRIAL (CALGB 150007/150012, ACRIN 6657, InterSPORE Trial). Breast Cancer Res Treat. 2012 Apr;132(3):871-9. doi: 10.1007/s10549-011-1670-4. Epub 2011 Jul 28.
- Esserman LJ, Berry DA, Cheang MC, Yau C, Perou CM, Carey L, DeMichele A, Gray JW, Conway-Dorsey K, Lenburg ME, Buxton MB, Davis SE, van't Veer LJ, Hudis C, Chin K, Wolf D, Krontiras H, Montgomery L, Tripathy D, Lehman C, Liu MC, Olopade OI, Rugo HS, Carpenter JT, Livasy C, Dressler L, Chhieng D, Singh B, Mies C, Rabban J, Chen YY, Giri D, Au A, Hylton N; I-SPY 1 TRIAL Investigators. Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat. 2012 Apr;132(3):1049-62. doi: 10.1007/s10549-011-1895-2. Epub 2011 Dec 25.
- Osdoit M, Yau C, Symmans WF, Boughey JC, Ewing CA, Balassanian R, Chen YY, Krings G, Wallace AM, Zare S, Fadare O, Lancaster R, Wei S, Godellas CV, Tang P, Tuttle TM, Klein M, Sahoo S, Hieken TJ, Carter JM, Chen B, Ahrendt G, Tchou J, Feldman M, Tousimis E, Zeck J, Jaskowiak N, Sattar H, Naik AM, Lee MC, Rosa M, Khazai L, Rendi MH, Lang JE, Lu J, Tawfik O, Asare SM, Esserman LJ, Mukhtar RA. Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial. JAMA Surg. 2022 Nov 1;157(11):1034-1041. doi: 10.1001/jamasurg.2022.4118.
- Symmans WF, Yau C, Chen YY, Balassanian R, Klein ME, Pusztai L, Nanda R, Parker BA, Datnow B, Krings G, Wei S, Feldman MD, Duan X, Chen B, Sattar H, Khazai L, Zeck JC, Sams S, Mhawech-Fauceglia P, Rendi M, Sahoo S, Ocal IT, Fan F, LeBeau LG, Vinh T, Troxell ML, Chien AJ, Wallace AM, Forero-Torres A, Ellis E, Albain KS, Murthy RK, Boughey JC, Liu MC, Haley BB, Elias AD, Clark AS, Kemmer K, Isaacs C, Lang JE, Han HS, Edmiston K, Viscusi RK, Northfelt DW, Khan QJ, Leyland-Jones B, Venters SJ, Shad S, Matthews JB, Asare SM, Buxton M, Asare AL, Rugo HS, Schwab RB, Helsten T, Hylton NM, van 't Veer L, Perlmutter J, DeMichele AM, Yee D, Berry DA, Esserman LJ. Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial. JAMA Oncol. 2021 Nov 1;7(11):1654-1663. doi: 10.1001/jamaoncol.2021.3690.
- Perez-Garcia J, Soberino J, Racca F, Gion M, Stradella A, Cortes J. Atezolizumab in the treatment of metastatic triple-negative breast cancer. Expert Opin Biol Ther. 2020 Sep;20(9):981-989. doi: 10.1080/14712598.2020.1769063. Epub 2020 May 25.
- Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark A, Albain K, Boughey JC, Jaskowiak NT, Elias A, Isaacs C, Kemmer K, Helsten T, Majure M, Stringer-Reasor E, Parker C, Lee MC, Haddad T, Cohen RN, Asare S, Wilson A, Hirst GL, Singhrao R, Steeg K, Asare A, Matthews JB, Berry S, Sanil A, Schwab R, Symmans WF, van 't Veer L, Yee D, DeMichele A, Hylton NM, Melisko M, Perlmutter J, Rugo HS, Berry DA, Esserman LJ. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial. JAMA Oncol. 2020 May 1;6(5):676-684. doi: 10.1001/jamaoncol.2019.6650.
- Chien AJ, Tripathy D, Albain KS, Symmans WF, Rugo HS, Melisko ME, Wallace AM, Schwab R, Helsten T, Forero-Torres A, Stringer-Reasor E, Ellis ED, Kaplan HG, Nanda R, Jaskowiak N, Murthy R, Godellas C, Boughey JC, Elias AD, Haley BB, Kemmer K, Isaacs C, Clark AS, Lang JE, Lu J, Korde L, Edmiston KK, Northfelt DW, Viscusi RK, Yee D, Perlmutter J, Hylton NM, Van't Veer LJ, DeMichele A, Wilson A, Peterson G, Buxton MB, Paoloni M, Clennell J, Berry S, Matthews JB, Steeg K, Singhrao R, Hirst GL, Sanil A, Yau C, Asare SM, Berry DA, Esserman LJ; I-SPY 2 Consortium. MK-2206 and Standard Neoadjuvant Chemotherapy Improves Response in Patients With Human Epidermal Growth Factor Receptor 2-Positive and/or Hormone Receptor-Negative Breast Cancers in the I-SPY 2 Trial. J Clin Oncol. 2020 Apr 1;38(10):1059-1069. doi: 10.1200/JCO.19.01027. Epub 2019 Feb 7.
- Severson TM, Wolf DM, Yau C, Peeters J, Wehkam D, Schouten PC, Chin SF, Majewski IJ, Michaut M, Bosma A, Pereira B, Bismeijer T, Wessels L, Caldas C, Bernards R, Simon IM, Glas AM, Linn S, van 't Veer L. The BRCA1ness signature is associated significantly with response to PARP inhibitor treatment versus control in the I-SPY 2 randomized neoadjuvant setting. Breast Cancer Res. 2017 Aug 25;19(1):99. doi: 10.1186/s13058-017-0861-2.
- Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ; I-SPY 2 Investigators. Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer. N Engl J Med. 2016 Jul 7;375(1):23-34. doi: 10.1056/NEJMoa1513749.
- Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive Randomization of Neratinib in Early Breast Cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. doi: 10.1056/NEJMoa1513750.
- Trapani D, Ferraro E, Giugliano F, Boscolo Bielo L, Curigliano G, Burstein HJ. Postneoadjuvant treatment for triple-negative breast cancer. Curr Opin Oncol. 2022 Nov 1;34(6):623-634. doi: 10.1097/CCO.0000000000000893. Epub 2022 Aug 19.
- Wolf DM, Yau C, Wulfkuhle J, Brown-Swigart L, Gallagher RI, Lee PRE, Zhu Z, Magbanua MJ, Sayaman R, O'Grady N, Basu A, Delson A, Coppe JP, Lu R, Braun J; I-SPY2 Investigators; Asare SM, Sit L, Matthews JB, Perlmutter J, Hylton N, Liu MC, Pohlmann P, Symmans WF, Rugo HS, Isaacs C, DeMichele AM, Yee D, Berry DA, Pusztai L, Petricoin EF, Hirst GL, Esserman LJ, van 't Veer LJ. Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies. Cancer Cell. 2022 Jun 13;40(6):609-623.e6. doi: 10.1016/j.ccell.2022.05.005. Epub 2022 May 26.
- Engebraaten O, Yau C, Berg K, Borgen E, Garred O, Berstad MEB, Fremstedal ASV, DeMichele A, Veer LV', Esserman L, Weyergang A. RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer. Nat Commun. 2021 Nov 5;12(1):6427. doi: 10.1038/s41467-021-26018-z.
- I-SPY2 Trial Consortium; Yee D, DeMichele AM, Yau C, Isaacs C, Symmans WF, Albain KS, Chen YY, Krings G, Wei S, Harada S, Datnow B, Fadare O, Klein M, Pambuccian S, Chen B, Adamson K, Sams S, Mhawech-Fauceglia P, Magliocco A, Feldman M, Rendi M, Sattar H, Zeck J, Ocal IT, Tawfik O, LeBeau LG, Sahoo S, Vinh T, Chien AJ, Forero-Torres A, Stringer-Reasor E, Wallace AM, Pusztai L, Boughey JC, Ellis ED, Elias AD, Lu J, Lang JE, Han HS, Clark AS, Nanda R, Northfelt DW, Khan QJ, Viscusi RK, Euhus DM, Edmiston KK, Chui SY, Kemmer K, Park JW, Liu MC, Olopade O, Leyland-Jones B, Tripathy D, Moulder SL, Rugo HS, Schwab R, Lo S, Helsten T, Beckwith H, Haugen P, Hylton NM, Van't Veer LJ, Perlmutter J, Melisko ME, Wilson A, Peterson G, Asare AL, Buxton MB, Paoloni M, Clennell JL, Hirst GL, Singhrao R, Steeg K, Matthews JB, Asare SM, Sanil A, Berry SM, Esserman LJ, Berry DA. Association of Event-Free and Distant Recurrence-Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomized Clinical Trial. JAMA Oncol. 2020 Sep 1;6(9):1355-1362. doi: 10.1001/jamaoncol.2020.2535.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Sarcoma
- Neoplasms, Vascular Tissue
- Breast Neoplasms
- Triple Negative Breast Neoplasms
- Hemangiosarcoma
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Poly(ADP-ribose) Polymerase Inhibitors
- Antibiotics, Antineoplastic
- Hormone Antagonists
- Immune Checkpoint Inhibitors
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Topoisomerase I Inhibitors
- Immunoconjugates
- Immunotoxins
- Carboplatin
- Paclitaxel
- Trastuzumab
- Olaparib
- Letrozole
- Durvalumab
- Pembrolizumab
- Irinotecan
- Metformin
- Albumin-Bound Paclitaxel
- Doxorubicin
- Veliparib
- Antibodies, Monoclonal
- Ado-Trastuzumab Emtansine
- Pertuzumab
- Cemiplimab
- Tucatinib
- Talazoparib
- Trebananib
- Dostarlimab
- SGN-LIV1A
Other Study ID Numbers
- 097517
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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