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.
Brief Title
I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
(855) 866-0505
Central Contact Email
w.chang@quantumleaphealth.org
Central Contact Role
Contact
Central Contact Email
m.pitsiouni@quantumleaphealth.org
Completion Date
Completion Date Type
Estimated
Conditions
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
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
* 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
Inclusion 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)
* 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)
Gender
All
Gender Based
false
Keywords
Neoadjuvant
Breast
Cancer
Neoplasm
Adaptive
pCR
Pathologic Complete Response
Biomarkers signature
MRI Volume
Endocrine Therapy
Chemotherapy
Immunotherapy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01042379
Org Class
Other
Org Full Name
QuantumLeap Healthcare Collaborative
Org Study Id
097517
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
Primary Outcomes
Outcome Measure
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.
Outcome Time Frame
Post surgery based on upto 36-week treatment
Secondary Outcomes
Outcome Time Frame
Blood and Tissue Collection: Baseline, Post-Randomization, Pre-AC, Pre- and Post-Surgery
Outcome Measure
Establishing predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB).
Outcome Time Frame
Three- and Five-Year Post-surgery Follow-up
Outcome Measure
To determine three- and five-year relapse-free survival (RFS) and OS among the treatment arms.
Outcome Time Frame
Post-Randomization, Pre-AC, Pre-Surgery, Post-Surgery upto One Year during follow-up
Outcome Measure
To determine incidence of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested.
Outcome Time Frame
Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery
Outcome Measure
MRI Volume
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jesus Anampa Mesias
Investigator Email
janampa@montefiore.org
Investigator Phone
718-920-4826/718-405-8505/646-757-0997