Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

I-SPY 2 TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by QuantumLeap Healthcare Collaborative
Sponsor:
Information provided by (Responsible Party):
QuantumLeap Healthcare Collaborative
ClinicalTrials.gov Identifier:
NCT01042379
First received: December 31, 2009
Last updated: October 13, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Breast Neoplasms
Breast Cancer
Breast Tumors
Drug: Standard Therapy
Drug: AMG 386
Drug: AMG 479 (Ganitumab) plus Metformin
Drug: MK-2206 with or without Trastuzumab
Drug: AMG 386 and Trastuzumab
Drug: T-DM1 and Pertuzumab
Drug: Pertuzumab and Trastuzumab
Drug: Ganetespib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: I-SPY 2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)

Resource links provided by NLM:


Further study details as provided by QuantumLeap Healthcare Collaborative:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • MRV [ Time Frame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 800
Study Start Date: March 2010
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard Therapy
Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
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
Experimental: AMG 386
Novel investigational agent
Drug: AMG 386
15 mg/kg IV every week during 12 weekly treatment cycles post-randomization
Experimental: AMG 479 plus Metformin
Novel investigational agent
Drug: AMG 479 (Ganitumab) plus Metformin
AMG 479 (Ganitumab) 12 mg/kg IV every 2 weeks during 12 week treatment cycle post-randomization; Metformin: 850 mg po every week during 12 weekly treatment cycles post-randomization
Other Name: Ganitumab
Experimental: MK-2206 with or without Trastuzumab
Novel investigational agent
Drug: MK-2206 with or without Trastuzumab
MK-2206: 135 mg every week during 12 weekly treatment cycles post-randomization; Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
Experimental: AMG 386 and Trastuzumab
Novel Investigational Agent
Drug: AMG 386 and Trastuzumab
AMG 386: 15 mg/kg IV every week during 12 weekly treatment cycles post-randomization; Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
Experimental: T-DM1 and Pertuzumab
Novel Investigational Agent
Drug: T-DM1 and Pertuzumab
T-DM1: 3.6 mg/kg IV every 2 weeks (weeks 1, 4, 7, 10) post-randomization; Pertuzumab: 840 mg IV (loading dose) week 1 and 420 mg every 3 weeks (weeks 4, 7, 10) post-randomization
Experimental: Pertuzumab and Trastuzumab
Novel Investigational Agent
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
Experimental: Ganetespib
Novel investigational Agent
Drug: Ganetespib
150 mg/m2 once weekly for 3 out of 4 weeks (Days 1, 8, 15 every 28 days)

Detailed Description:

I-SPY 2 will compare the efficacy of novel drugs in combination with standard chemotherapy with the efficacy of standard therapy alone. The goal is identify improved treatment regimens for subsets on the basis of molecular characteristics (biomarker signatures) of their disease. As described for previous adaptive trials, regimens that show a high Bayesian predictive probability of being more effective than standard therapy will graduate from the trial with their corresponding biomarker signature(s). Regimens 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 are graduated or dropped.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01042379

Contacts
Contact: Meredith Buxton, MPH, PhD, I-SPY Exec. Dir. 415-353-7357 meredith.buxton@ucsfmedctr.org

  Show 23 Study Locations
Sponsors and Collaborators
QuantumLeap Healthcare Collaborative
Investigators
Principal Investigator: Laura Esserman, MD, MBA University of California, San Francisco (UCSF)
  More Information

Additional Information:
Publications:
Responsible Party: QuantumLeap Healthcare Collaborative
ClinicalTrials.gov Identifier: NCT01042379     History of Changes
Other Study ID Numbers: 097517
Study First Received: December 31, 2009
Last Updated: October 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by QuantumLeap Healthcare Collaborative:
I-SPY 2
Neoadjuvant
Breast
Cancer
Neoplasm
Adaptive
pCR
Pathologic Complete Response
MRV
Biomarkers signature
MRI

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Metformin
Pertuzumab
Trastuzumab
Antineoplastic Agents
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014