I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer

Breast Cancer Clinical Trial

— I-SPY  

Official title:

I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01042379
• Other study ID #: 097517
• Status: Recruiting
• Phase: Phase 2
• Start date: March 1, 2010
• Est. completion date: December 2031

Study information

• Verified date: April 2024
• Source: QuantumLeap Healthcare Collaborative
• Contact: Won Chang
• Phone: (855) 866-0505
• Email: w.chang[@]quantumleaphealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to further advance the ability to practice personalized medicine by learning which new drug agents are most effective with which types of breast cancer tumors and by learning more about which early indicators of response (tumor analysis prior to surgery via magnetic resonance imaging (MRI) images along with tissue and blood samples) are predictors of treatment success.

Description:

I-SPY2 will assess the efficacy of novel drugs in sequence with standard chemotherapy. The goal is identify treatment strategies for subsets on the basis of molecular characteristics (biomarker signatures) of their disease with high estimated pCR rate. As described for previous adaptive trials, novel regimens with sufficiently high activities alone and contribute to treatment strategies that show a high Bayesian predictive probability of being more effective than the dynamic control will graduate from the trial with their corresponding biomarker signature(s). Treatment strategies will be dropped if they show a low probability of improved efficacy with any biomarker signature. New drugs will enter as those that have undergone testing complete their evaluation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: December 2031
• Est. primary completion date: December 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Angiosarcoma
• Breast Cancer
• Breast Neoplasms
• Breast Tumors
• Early-stage Breast Cancer
• HER2-negative Breast Cancer
• HER2-positive Breast Cancer
• Hormone Receptor Positive Tumor
• Locally Advanced Breast Cancer
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Standard Therapy
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
• AMG 386 with or without Trastuzumab
Arm is closed.
• AMG 479 (Ganitumab) plus Metformin
Arm is closed.
• MK-2206 with or without Trastuzumab
Arm is closed.
• AMG 386 and Trastuzumab
Arm is closed.
• T-DM1 and Pertuzumab
Arm is closed.
• Pertuzumab and Trastuzumab
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
• Ganetespib
Arm is closed.
• ABT-888
Arm is closed.
• Neratinib
Arm is closed.
• PLX3397
Arm is closed.
• Pembrolizumab - 4 cycle
Arm is closed.
• Talazoparib plus Irinotecan
Arm is closed.
• Patritumab and Trastuzumab
Arm is closed.
• Pembrolizumab - 8 cycle
Arm is closed.
• SGN-LIV1A
Arm is closed. SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16
• Durvalumab plus Olaparib
Arm is closed.
• SD-101 + Pembrolizumab
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
• Tucatinib plus trastuzumab and pertuzumab
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
• Cemiplimab
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
• Cemiplimab plus REGN3767
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
• Trilaciclib with or without trastuzumab + pertuzumab
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
• SYD985 ([vic-]trastuzumab duocarmazine)
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
• 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
• Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) 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 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
• Amcenestrant
Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks
• Amcenestrant + Abemaciclib
Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Abemaciclib (Verzenio), 150mg BID, p.o., for 24 weeks
• Amcenestrant + Letrozole
Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Letrozole (Femara), 2.5mg QD, p.o., for 24 weeks
• ARX788
ARX788, 1.5 mg/kg Q3W, IV for 12 weeks
• ARX788 + Cemiplimab
ARX788, 1.5 mg/kg Q3W, IV for 12 weeks Cemiplimab, 350 mg Q3W, IV for 12 weeks
• VV1 + Cemiplimab
VV1, 3x10^9 TCID50 once (day-8), Intra-tumoral injection Cemiplimab, 350 mg Q3W, IV for 12 weeks
• Datopotamab deruxtecan
Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks
• Datopotamab deruxtecan + Durvalumab
Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks Durvalumab, 1120 mg Q3W, IV for 12 weeks
• Zanidatamab
Zanidatamab: Flat dose of 1,200mg Q2W for 12 weeks
• Lasofoxifene
Lasofoxifene: 5.0 mg QD, p.o., for 24 weeks
• Z-endoxifen
Z-endoxifen: 10 mg QD, p.o., for 24 weeks
• ARV-471
ARV-471: 200 mg QD, p.o, for 24 weeks
• ARV-471 + Letrozole
ARV-471: 200 mg QD, p.o, for 24 weeks Letrozole: 2.5 mg QD, p.o, for 24 weeks

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Texas, Southwestern Medical Center	Dallas	Texas
United States	City of Hope	Duarte	California
United States	Inova Health System	Falls Church	Virginia
United States	University of Texas, M.D. Anderson Cancer Center	Houston	Texas
United States	University of California San Diego	La Jolla	California
United States	Herbert-Herman Cancer Center, Sparrow Hospital	Lansing	Michigan
United States	University of Southern California	Los Angeles	California
United States	Loyola University	Maywood	Illinois
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale Cancer Center	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Laura and Isaac Perlmutter Cancer Center / NYU Langone Health	New York	New York
United States	HOAG Memorial Hospital Presbyterian	Newport Beach	California
United States	University of Pennsylvania (U Penn)	Philadelphia	Pennsylvania
United States	University Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science Institute (OHSU)	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Wilmot Cancer Institute	Rochester	New York
United States	University of California San Francisco (UCSF)	San Francisco	California
United States	Mayo Clinic - Scottsdale	Scottsdale	Arizona
United States	Swedish Cancer Institute	Seattle	Washington
United States	University of Washington	Seattle	Washington
United States	Sanford Clinical Research	Sioux Falls	South Dakota
United States	Moffitt Cancer Center	Tampa	Florida
United States	University of Arizona	Tucson	Arizona
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	University of Kansas	Westwood	Kansas
United States	Wake Forest Baptist Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
QuantumLeap Healthcare Collaborative

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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, Carpe — View Citation

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 — View Citation

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. — View Citation

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 — View Citation

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: res — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Post surgery based on upto 36-week treatment
Secondary	Establishing predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB).		Blood and Tissue Collection: Baseline, Post-Randomization, Pre-AC, Pre- and Post-Surgery
Secondary	To determine three- and five-year relapse-free survival (RFS) and OS among the treatment arms.		Three- and Five-Year Post-surgery Follow-up
Secondary	To determine incidence of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested.		Post-Randomization, Pre-AC, Pre-Surgery, Post-Surgery upto One Year during follow-up
Secondary	MRI Volume		Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery

External Links

•   Abstract CT227 AACR 2014
•   Abstract P1-14-03; SABCC 2015
•   Abstract S5-02 SABCC 2014
•   I-SPY 2 TRIAL Website