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PRE-Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis: A Phase I/II Platform Trial

Status: Recruiting
Location: See all (10) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

PRE-ISPY Phase I/II (I-SPY-P1) is an open-label, multisite platform study with multiple ongoing drug regimen arms added by protocol amendment which is designed to evaluate single agents or combinations in locally advanced, incurable, or metastatic solid tumors and/or oligometastatic malignancy and/or a high risk of recurrence following prior treatment with curative intent. The overall goal is moving promising drug regimens into a larger phase II (or III) trial and in general could feed the neoadjuvant breast I-SPY 2 Trial (NCT01042379) and/or other oncology solid tumor trial in a timely manner.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• GIC1: The participant must have ability to understand and willingness to provide signed written informed consent prior to any study related assessments and procedures and for collection of archival FFPE blocks for research. If FFPE blocks cannot be submitted, 20 to 40 freshly cut FFPE tissue slices (4 to 7 microns thick each) from a representative FFPE block, mounted on charged glass slides and left unstained will be acceptable. This criteria can be modified in specific drug regimens.

• GIC2: Age ≥ 18 years at the time of signing the informed consent

• GIC3: Gender: Male or female (premenopausal and postmenopausal)

• GIC4: ECOG performance status Grade 0-2. This criteria can be modified in specific drug regimens.

• GIC5: Estimated life expectancy \> 12 weeks at the start of investigational medicinal product (IMP) treatment.

• GIC6: Adequate organ function, evidenced by the following laboratory results within 30 days of the start of IMP:

‣ Absolute neutrophil count ≥ 1,500/mm3

⁃ Platelet count ≥ 100,000/mm3

⁃ Hemoglobin ≥ 9.0 g/dL with no blood transfusion in the past 28 days

⁃ Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)

⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN

⁃ Estimated Creatinine clearance (using Cockcroft-Gault formula) ≥ 60 mL/min for small molecules and \>30 mL/min for monoclonal antibodies unless otherwise specified in the Arm Specific Eligibility.

∙ These cut-off values may be modified with supporting data for specific drug regimens.

• GIC7: Non-Pregnant: Serum or urine pregnancy test must be negative within 14 days of IMP treatment start in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before enrollment, or who have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation. If male, they must agree to refrain from donating sperm during treatment.

• GIC8: Contraception: Women of childbearing potential and men must be willing to use adequate contraception for the duration of protocol treatment. Additional information regarding contraception for the specific treatment arm will be added to the drug arm description. Adequate contraception is defined as one highly effective form (i.e., abstinence, (fe)male sterilization) OR two effective forms (e.g., non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream / suppository).

• GIC9: Prior therapy effects: Resolution of all acute toxic effects of prior therapy, including radiotherapy, to grade ≤1 and neuropathy to grade ≤2 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures.

• GIC10: Participant compliance: Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

• Additional arm specific inclusion criteria as needed by drug arm regimen

Locations
United States
Alabama
The University of Alabama at Birmingham O'Neal Comprehensive Cancer Center
RECRUITING
Birmingham
Arizona
Mayo Clinic Comprehensive Cancer Center
NOT_YET_RECRUITING
Phoenix
Colorado
University of Colorado Cancer Center
ACTIVE_NOT_RECRUITING
Aurora
Florida
Moffitt Cancer Center
ACTIVE_NOT_RECRUITING
Tampa
Illinois
The University of Chicago Medicine Comprehensive Cancer Center
RECRUITING
Chicago
UChicago Medicine Comprehensive Cancer Center at Silver Cross Hospital
RECRUITING
New Lenox
UChicago Medicine Orland Park
RECRUITING
Orland Park
Minnesota
University of Minnesota Masonic Cancer Center
RECRUITING
Minneapolis
Mayo Clinic Comprehensive Cancer Center
NOT_YET_RECRUITING
Rochester
Texas
The University of Texas MD Anderson Cancer Center
ACTIVE_NOT_RECRUITING
Houston
Contact Information
Primary
Smita M Asare
smita.asare@qlhc.org
(855) 866-0505
Backup
Maria Pitsiouni, PhD
m.pitsiouni@qlhc.org
(415) 651-8047
Time Frame
Start Date: 2023-02-15
Estimated Completion Date: 2031-12-30
Participants
Target number of participants: 280
Treatments
Experimental: PRE1 ALX148 (Evorpacept) + Fam-Trastuzumab Deruxtecan-Nxki (T-DXd, Enhertu®)
The combination of T-DXd and ALX148 aims to explore the anti-tumoral effects of trastuzumab, of the topoisomerase inhibitor DXd and of the CD47-blocking agent ALX148. The rationale for this combination is that ALX148 is hypothesized, based on preclinical data, to facilitate antibody-dependent cellular phagocytosis (ADCP) of HER2 expressing (\>HER2 1+) breast cancer binding T-DXd while cancer cell intrinsic or bystander cytotoxicity of T-DXd will result in the release of neoantigens promoting immune mediated antitumor activity in the tumor microenvironment.
Experimental: PRE2 Zanidatamab (Ziihera®, ZW25, zani) + Tucatinib (TUKYSA®)
Zanidatamab is a bispecific IgG1-like antibody directed against two distinct HER2 epitopes. It induces formation of receptor clusters and internalization resulting in downregulation. It also inhibits growth factor-dependent and -independent tumor cell proliferation and potently activates ADCC, ADCP, and CDC. FDA approved for metastatic HER2+ bile duct cancer.~Tucatinib is a highly selective, small molecule tyrosine kinase inhibitor (TKI) of HER2 compared to other TKI's (i.e., EGFR). It is well tolerated, crosses the blood brain barrier and can treat CNS disease. FDA approved for HER2+ breast cancer.~Given the promising clinical data for each of these drugs which have different mechanisms, the effect of zanidatamab after T-DXd (Enhertu®) in breast cancer patients, and the favorable toxicity profile of both drugs, we hypothesize that the combination of tucatinib and zanidatamab will be well tolerated and more efficacious than either drug alone for the treatment of HER2+ breast cancer.
Experimental: PRE4 TTX-MC138
TTX-MC138 is an antisense oligonucleotide targeting miR-10b. MicroRNA-10b (miR-10b) was identified in metastatic cell lines and tumors from participants with metastatic breast cancer and has been shown to regulate the ability of metastatic tumor cells to survive outside of the primary tumor and to migrate and invade surrounding tissue. miRNA-10b is critical to tumor growth and is a master regulator of metastatic cell viability in a range of cancers, including breast, pancreatic, ovarian, colon cancer, glioblast.~This is a PRE-ISPY PHASE II study of TTX-MC138 as interception treatment in patients with Stage I-III adenocarcinoma of the colon or rectum (Cohort A) who have documented minimal residual disease by tumor informed ctDNA, that was collected following completion of standard therapy with curative intent.
Related Therapeutic Areas
Sponsors
Collaborators: Pfizer, Jazz Pharmaceuticals, ALX Oncology Inc., TransCode Therapeutics
Leads: QuantumLeap Healthcare Collaborative

This content was sourced from clinicaltrials.gov

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