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

• ClinicalTrials.gov Identifier: NCT01042379
• Recruitment Status: Recruiting
• First Posted: January 5, 2010
• Last Update Posted: March 24, 2023
• Sponsor: QuantumLeap Healthcare Collaborative
• Information provided by (Responsible Party): QuantumLeap Healthcare Collaborative

Tracking Information

• First Submitted Date: December 31, 2009
• First Posted Date: January 5, 2010
• Last Update Posted Date: March 24, 2023
• Actual Study Start Date: March 1, 2010
• Estimated Primary Completion Date: December 2030 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 17, 2022): 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 ]
• Original Primary Outcome Measures (submitted: January 4, 2010): 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 24-week treatment ]

Current Secondary Outcome Measures (submitted: July 11, 2016)

• 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 ]
• 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 ]
• 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 ]
• MRI Volume [ Time Frame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery ]

Original Secondary Outcome Measures (submitted: January 4, 2010)

• 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 ]
• 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 ]
• 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 ]
• MRV [ Time Frame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
• Official Title: I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
• Brief 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.
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

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
  Other Name: Paclitaxel (Taxol); Doxorubicin (Adriamycin)
• Drug: AMG 386 with or without Trastuzumab
  Arm is closed.
  Other Name: AMG 386 (Trebananib); (Trastuzumab) Herceptin
• Drug: AMG 479 (Ganitumab) plus Metformin
  Arm is closed.
  Other Name: Ganitumab
• Drug: MK-2206 with or without Trastuzumab
  Arm is closed.
  Other Name: (Trastuzumab) Herceptin
• Drug: AMG 386 and Trastuzumab
  Arm is closed.
  Other Name: AMG 386 (Trebananib); Trastuzumab (Herceptin)
• Drug: T-DM1 and Pertuzumab
  Arm is closed.
  Other Name: T-DM1 (Trastuzumab emtansine); Pertuzumab (Perjeta)
• Drug: 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
  Other Name: Pertuzumab (Perjeta); Trastuzumab (Herceptin)
• Drug: Ganetespib
  Arm is closed.
• Drug: ABT-888
  Arm is closed.
  Other Name: Veliparib
• Drug: Neratinib
  Arm is closed.
• Drug: PLX3397
  Arm is closed.
• Drug: Pembrolizumab - 4 cycle
  Arm is closed.
• Drug: Talazoparib plus Irinotecan
  Arm is closed.
• Drug: Patritumab and Trastuzumab
  Arm is closed.
• Drug: Pembrolizumab - 8 cycle
  Arm is closed.
• Drug: SGN-LIV1A
  Arm is closed. SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16
• Drug: Durvalumab plus Olaparib
  Arm is closed.
• Drug: 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
• Drug: 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
• Drug: 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
• Drug: 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
• Drug: 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

  Other Name: Trilaciclib (G1T28); Pertuzumab (Perjeta); Trastuzumab (Herceptin)
• Drug: 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
• 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 Name: Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)
• Drug: 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

  Other Name: Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)
• Drug: Amcenestrant
  Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks
  Other Name: SAR439859
• Drug: Amcenestrant + Abemaciclib
  Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Abemaciclib (Verzenio), 150mg BID, p.o., for 24 weeks
  Other Name: Amcenestrant (SAR439859), Abemaciclib (Verzenio)
• Drug: Amcenestrant + Letrozole
  Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Letrozole (Femara), 2.5mg QD, p.o., for 24 weeks
  Other Name: Amcenestrant (SAR439859), Letrozole (Femara)
• Drug: ARX788
  ARX788, 1.5 mg/kg Q3W, IV for 12 weeks
• Drug: ARX788 + Cemiplimab
  ARX788, 1.5 mg/kg Q3W, IV for 12 weeks Cemiplimab, 350 mg Q3W, IV for 12 weeks
• Drug: VV1 + Cemiplimab
  VV1, 3x10^9 TCID50 once (day-8), Intra-tumoral injection Cemiplimab, 350 mg Q3W, IV for 12 weeks
  Other Names:

  • VOYAGER V1™
  • VSV-IFNβ-NIS
• Drug: Datopotamab deruxtecan
  Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks
  Other Name: Dato-DXd
• Drug: Datopotamab deruxtecan + Durvalumab
  Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks Durvalumab, 1120 mg Q3W, IV for 12 weeks
  Other Name: Dato-DXd
• Drug: Zanidatamab
  Zanidatamab: Flat dose of 1,200mg Q2W for 12 weeks
• Drug: Lasofoxifene
  Lasofoxifene: 5.0 mg QD, p.o., for 24 weeks
• Drug: Z-endoxifen
  Z-endoxifen: 10 mg QD, p.o., for 24 weeks

Study Arms

• Active Comparator: Standard Therapy
  Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
  Intervention: Drug: Standard Therapy
• Experimental: AMG 386 with or without Trastuzumab
  Arm is closed.
  Interventions:

  • Drug: AMG 386 with or without Trastuzumab
  • Drug: AMG 386 and Trastuzumab
• AMG 479 plus Metformin
  Arm is closed.
  Intervention: Drug: AMG 479 (Ganitumab) plus Metformin
• Experimental: MK-2206 with or without Trastuzumab
  Arm is closed.
  Intervention: Drug: MK-2206 with or without Trastuzumab
• Experimental: T-DM1 and Pertuzumab
  Arm is closed.
  Intervention: Drug: T-DM1 and Pertuzumab
• Active Comparator: Pertuzumab and Trastuzumab
  Novel Control Investigational Agent. Arm is closed.
  Intervention: Drug: Pertuzumab and Trastuzumab
• Experimental: Ganetespib
  Arm is closed.
  Intervention: Drug: Ganetespib
• ABT-888
  Arm is closed.
  Intervention: Drug: ABT-888
• Neratinib
  Arm is closed.
  Intervention: Drug: Neratinib
• Experimental: PLX3397
  Arm is closed.
  Intervention: Drug: PLX3397
• Experimental: Pembrolizumab 4 cycle
  Arm is closed.
  Intervention: Drug: Pembrolizumab - 4 cycle
• Experimental: Talazoparib plus Irinotecan
  Arm is closed.
  Intervention: Drug: Talazoparib plus Irinotecan
• Experimental: Patritumab with or without Trastuzumab
  Arm is closed.
  Intervention: Drug: Patritumab and Trastuzumab
• Experimental: Pembrolizumab 8 cycle
  Arm is closed.
  Intervention: Drug: Pembrolizumab - 8 cycle
• Experimental: SGN-LIV1A
  Arm is closed.
  Intervention: Drug: SGN-LIV1A
• Experimental: Durvalumab plus Olaparib
  Arm is closed.
  Intervention: Drug: Durvalumab plus Olaparib
• Experimental: SD-101 + Pembrolizumab
  Arm is closed.
  Intervention: Drug: SD-101 + Pembrolizumab
• Experimental: Tucatinib
  Arm is closed.
  Intervention: Drug: Tucatinib plus trastuzumab and pertuzumab
• Experimental: Cemiplimab
  Novel Investigational Agent. Arm is closed.
  Intervention: Drug: Cemiplimab
• Experimental: Cemiplimab plus REGN3767
  Novel Investigational Agent. Arm is closed.
  Intervention: Drug: Cemiplimab plus REGN3767
• Experimental: Trilaciclib with or without trastuzumab + pertuzumab
  Novel Investigational Agent. Arm is closed.
  Intervention: Drug: Trilaciclib with or without trastuzumab + pertuzumab
• Experimental: SYD985 ([vic-]trastuzumab duocarmazine)
  Novel Investigational Agent. Arm is closed.
  Intervention: Drug: SYD985 ([vic-]trastuzumab duocarmazine)
• Experimental: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
  Novel Investigational Agent. Arm is closed.
  Intervention: Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
• Experimental: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab
  Novel Investigational Agent. Arm is closed.
  Intervention: Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab
• Experimental: Endocrine Optimization Pilot: Amcenestrant Monotherapy
  Novel Investigational Agent. Arm is closed.
  Intervention: Drug: Amcenestrant
• Experimental: Endocrine Optimization Pilot: Amcenestrant + Abemaciclib
  Novel Investigational Agent. Arm is closed.
  Intervention: Drug: Amcenestrant + Abemaciclib
• Experimental: Endocrine Optimization Pilot: Amcenestrant + Letrozole
  Novel Investigational Agent. Arm is closed.
  Intervention: Drug: Amcenestrant + Letrozole
• Experimental: ARX788 in Block A and followed by SOC in Block B
  Novel investigational Agent followed by SOC
  Intervention: Drug: ARX788
• Experimental: ARX788 + Cemiplimab in Block A and followed by SOC in Block B
  Novel investigational Agent followed by SOC. Arm is closed.
  Intervention: Drug: ARX788 + Cemiplimab
• Experimental: VSV-IFNβ-NIS (VOYAGER V1™; VV1) + Cemiplimab in Block A and followed by SOC in block B
  Novel investigational Agent followed by SOC
  Intervention: Drug: VV1 + Cemiplimab
• Experimental: Datopotamab Deruxtecan in Block A and followed by SOC in block B
  Novel investigational Agent followed by SOC
  Intervention: Drug: Datopotamab deruxtecan
• Experimental: Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block B
  Novel investigational Agent followed by SOC
  Intervention: Drug: Datopotamab deruxtecan + Durvalumab
• Experimental: Zanidatamab in Block A and followed by SOC in block B
  Novel investigational Agent followed by SOC
  Intervention: Drug: Zanidatamab
• Experimental: Endocrine Optimization Pilot: Lasofoxifene
  Novel investigational Agent
  Intervention: Drug: Lasofoxifene
• Experimental: Endocrine Optimization Pilot: (Z)-Endoxifen
  Novel investigational Agent
  Intervention: Drug: Z-endoxifen

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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 17, 2022): 5000
• Original Estimated Enrollment (submitted: January 4, 2010): 800
• Estimated Study Completion Date: December 2031
• Estimated Primary Completion Date: December 2030 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Won Chang; (855) 866-0505; w.chang@quantumleaphealth.org

Contact: Maria Pitsiouni, PhD; m.pitsiouni@quantumleaphealth.org

• Listed Location Countries: United States
• Removed Location Countries: Canada

Administrative Information

• NCT Number: NCT01042379
• Other Study ID Numbers: 097517
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: QuantumLeap Healthcare Collaborative
• Original Responsible Party: Amy McGuire Porter, Executive Director, FNIH
• Current Study Sponsor: QuantumLeap Healthcare Collaborative
• Original Study Sponsor: Foundation for the National Institutes of Health
• Collaborators: Not Provided

Investigators

• Principal Investigator: Laura Esserman, MD, MBA; University of California, San Francisco

• PRS Account: QuantumLeap Healthcare Collaborative
• Verification Date: March 2023