BLU-222 for Solid Cancers
Recruiting in Palo Alto (17 mi)
+22 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Waitlist Available
Sponsor: Blueprint Medicines Corporation
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of BLU-222, a selective inhibitor of CDK2.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you must stop all current medications, but you cannot take any prohibited medications or herbal remedies that cannot be stopped at least 2 weeks before starting the study drug.
What data supports the idea that BLU-222 for Solid Cancers is an effective drug?
The available research does not provide any specific data on the effectiveness of BLU-222 for Solid Cancers. Instead, it focuses on other treatments for metastatic breast cancer, such as combinations of docetaxel, bevacizumab, and other drugs. Without direct data on BLU-222, we cannot compare its effectiveness to these other treatments.
12345What safety data is available for BLU-222 in solid cancers?
The provided research does not contain any safety data for BLU-222 or its variants. The studies focus on other treatments such as eribulin, paclitaxel, carboplatin, trastuzumab, pertuzumab, and cisplatin, primarily in breast cancer patients. No information on BLU-222 is available in these abstracts.
678910Is the drug BLU-222 a promising treatment for solid cancers?
The drug BLU-222 is considered promising because it targets cancer stem cells, which are responsible for cancer growth and recurrence. By focusing on these cells, BLU-222 has the potential to improve cancer treatment outcomes and reduce the chances of the cancer coming back.
1112131415Eligibility Criteria
This trial is for adults with certain advanced solid tumors, including breast cancer, ovarian cancer, endometrial cancer, and stomach cancer that have worsened despite standard treatments. Participants must not be in a health crisis due to their tumor or have serious heart issues or uncontrolled infections. Women of childbearing potential and men must agree to use effective contraception.Inclusion Criteria
My endometrial or gastric cancer has worsened after 2 treatments, including a platinum-based therapy.
My cancer has worsened despite standard treatments.
My breast cancer is HR+ HER2- and worsened after CDK4/6 inhibitor treatment.
+1 more
Exclusion Criteria
I don't have lasting side effects from previous treatments.
I do not have serious heart problems like recent heart attacks or uncontrolled high blood pressure.
I do not have any major surgeries planned within 2 weeks of starting the study drug.
+12 more
Participant Groups
The study is testing BLU-222's safety and effectiveness against various cancers. It's an early-phase trial where patients will receive BLU-222 alone or combined with other drugs like Carboplatin, Ribociclib, or Fulvestrant to see how well they work together.
4Treatment groups
Experimental Treatment
Group I: BLU-222 MonotherapyExperimental Treatment2 Interventions
Dose Escalation: Multiple doses for BLU-222 for oral administration Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation
Group II: BLU-222 + Ribociclib + FulvestrantExperimental Treatment3 Interventions
Dose Escalation: Multiple doses for BLU-222 for oral administration at doses deemed appropriate based on BLU-222 Monotherapy arm along with Ribociclib and Fulvestrant at the approved doses.
Dose Expansion: Oral dose of BLU-222 as determined during dose escalation and approved doses of Ribociclib and Fulvestrant
Group III: BLU-222 + FulvestrantExperimental Treatment2 Interventions
Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation + fulvestrant at the approved dose
Group IV: BLU-222 + CarboplatinExperimental Treatment2 Interventions
Dose Escalation: Multiple doses for BLU-222 for oral administration at doses deemed appropriate based on BLU-222 Monotherapy arm and multiple doses of Carboplatin at the approved dose.
Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation and Carboplatin IV infusion at approved dose
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Virginia Comprehensive Cancer CenterCharlottesville, VA
Montefiore Medical CenterNew York, NY
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC)Baltimore, MD
UNC Hospitals at Chapel Hill - The University of North Carolina at Chapel HillChapel Hill, NC
More Trial Locations
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Who Is Running the Clinical Trial?
Blueprint Medicines CorporationLead Sponsor
References
Sequential addition of an anthracycline-based regimen to docetaxel as neoadjuvant chemotherapy in patients with operable breast cancer. [2018]The objective of this phase II study was to attempt to maximize response and survival in patients with bulky, operable breast cancer by combining sequential neoadjuvant docetaxel to a semi-intensive anthracycline-based regimen.
A phase II trial of docetaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer (TORI B01). [2020]Addition of the antiangiogenic agent bevacizumab to paclitaxel significantly improves response rates and progression-free survival for metastatic breast cancer (MBC). To assess the activity of docetaxel plus bevacizumab, a multicenter phase II trial was conducted.
A phase II trial of weekly paclitaxel, 5-fluorouracil, and leucovorin as first-line treatment for metastatic breast cancer. [2019]This phase II multicenter trial evaluated the efficacy and toxicity of weekly paclitaxel, 5-fluorouracil, and leucovorin administered as first-line therapy for metastatic breast cancer.
Phase II trial of doxorubicin and docetaxel plus granulocyte colony-stimulating factor in metastatic breast cancer: Eastern Cooperative Oncology Group Study E1196. [2022]The purpose of this multi-institutional phase II trial was to evaluate the efficacy and toxicity of doxorubicin and docetaxel plus granulocyte colony-stimulating factor (G-CSF) in patients with metastatic breast cancer. The primary objective was to determine whether the combination produced a response rate of at least 50%.
In the end what matters most? A review of clinical endpoints in advanced breast cancer. [2023]Many agents are being studied for the treatment of metastatic breast cancer (MBC), yet few studies have demonstrated longer overall survival (OS), the primary measure of clinical benefit in MBC. This paper examines the key endpoints in clinical trials and U.S. Food and Drug Administration (FDA) approvals of drugs for MBC. PubMed was searched (1980 to October 2009) for reports of phase III trials investigating chemotherapy and/or targeted therapy agents in MBC. FDA approval histories (1996-2009) for cytotoxic and biological agents indicated for MBC were reviewed. Of the 73 phase III MBC trials reviewed, a strikingly small proportion of trials demonstrated a gain in OS duration (12%, n = 9). OS gains were less frequently noted in first-line trials (8%) than in trials of second-line plus other lines of therapy (22%). Few trials were designed with the capacity to detect OS effects. Among 37 phase III trials conducted in the last 15 years, only three systemic therapies were approved for first-line use and nine were approved for use as second-line or other lines of therapy. Of these, only four were supported by results showing longer survival times. There is substantial discordance among the design and conduct of clinical trials, FDA drug approval, and the current view of OS as the ultimate measure of clinical benefit. There is an urgent need to reassess standards for clinical benefit in MBC and to establish guidelines for study design and conduct and drug approval. In the end, what matters most is ensuring rapid access to safe and effective oncology treatments.
Eribulin efficacy based on type of metastatic site: a real-life study in heavily pretreated metastatic breast cancer. [2017]The halichondrin B analog, eribulin, exerts an anticancer effect, as reported by several clinical and real-life studies on metastatic breast cancer patients. Here, we evaluated efficacy and safety of eribulin, focusing on response to treatment per metastasis type.
Efficacy and safety of eribulin in taxane-refractory patients in the 'real world'. [2017]Recent clinical, randomized and observational studies showed that eribulin, an analogous of Halichondrin B, was beneficial and well-tolerated in heavily pretreated metastatic breast cancer patients. Here, we aim to evaluate the effectiveness and safety of eribulin in taxane-refractory metastatic breast cancer patients.
Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study. [2022]In HER2-positive breast cancer (HER2+ BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC.
Clinical efficacy of weekly cisplatin for treatment of patients with breast cancer. [2022]We will investigate the efficacy and safety of weekly cisplatin (WC) for treatment of patients with breast cancer (BC) systematically.
Economic burden of selected adverse events in patients aged ≥65 years with metastatic renal cell carcinoma. [2018]To estimate the costs of adverse events (AEs) in patients aged ≥65 years with metastatic renal cell carcinoma (mRCC).
Simultaneous Targeting of Differentiated Breast Cancer Cells and Breast Cancer Stem Cells by Combination of Docetaxel- and Sulforaphane-Loaded Self-Assembled Poly(D, L-lactide-co-glycolide)/Hyaluronic Acid Block Copolymer-Based Nanoparticles. [2021]Breast cancer stem cells (BCSCs) are implicated in the initiation and progression of breast cancer and are responsible for metastasis and recurrence. In this study, we attempted to simultaneously target differentiated breast cancer cells (DBCCs) and BCSCs by using a combination of docetaxel (DTX)- and sulforaphane (SFN)-loaded poly(D, L-lactide-coglycolide)/hyaluronic acid (PLGA-b-HA)-based nanoparticles. BCSCs were identified as having an ESA+CD44+CD24– phenotype, which exhibited docetaxel resistance. Drug-loaded nanoparticles exhibited enhanced cytotoxicity towards both DBCCs and BCSCs compared with free drugs. SFN-loaded nanoparticles were more effective in inhibiting BCSCs than free SFN in vitro by down-regulating β-catenin expression. In vivo analysis of anti-tumor activity showed that the combination therapy with DTX- and SFN-loaded nanoparticles had the strongest antitumor efficacy. In vivo analysis of anti-BCSCs activity showed that the self-renewal ability of BCSCs was strongly inhibited in DTX- and SFN-loaded nanoparticle-treated groups. In conclusion, the combination of SFN- and DTX-loaded PLGA-b-HA nanoparticles shows therapeutic potential in the treatment of breast cancer by simultaneously targeting DBCCs and BCSCs.
Clinical implications of CD44+/CD24- tumor cell ratio in breast cancer. [2017]To investigate the association of the CD44+/CD24- cancer stem cell (CSC) ratio with clinicopathologic features and its prognostic value in breast cancer.
The flavonoid apigenin reduces prostate cancer CD44(+) stem cell survival and migration through PI3K/Akt/NF-κB signaling. [2022]Cancer stem cells (CSCs) are involved in drug resistance, metastasis and recurrence of cancers. The efficacy of apigenin on cell survival, apoptosis, migration and stemness properties were analyzed in CSCs.
Targeting Breast Cancer Stem Cells to Overcome Treatment Resistance. [2023]Despite advances in breast cancer diagnosis and treatment, many patients still fail therapy, resulting in disease progression, recurrence, and reduced overall survival. Historically, much focus has been put on the intrinsic subtyping based in the presence (or absence) of classical immunohistochemistry (IHC) markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-related protein (HER2). However, it is widely understood that tumors are composed of heterogeneous populations of cells with a hierarchical organization driven by cancer stem cells (CSCs). In breast tumors, this small population of cells displaying stem cell properties is known as breast CSCs (BCSCs). This rare population exhibit a CD44⁺/CD24-/low phenotype with high ALDH activity (ALDH⁺), and possesses higher tolerability to chemotherapy, hormone therapy, and radiotherapy and is able to reproduce the bulk of the tumor after reduction of cell populations sensitive to first-line therapy leading to disease relapse. In this review, we present special attention to BCSCs with future directions in the establishment of a therapy targeting this population. Drugs targeting the main BCSCs signaling pathways undergoing clinical trials are also summarized.
The therapeutic promise of the cancer stem cell concept. [2023]Cancer stem cells (CSCs) are a subpopulation of tumor cells that selectively possess tumor initiation and self-renewal capacity and the ability to give rise to bulk populations of nontumorigenic cancer cell progeny through differentiation. As we discuss here, they have been prospectively identified in several human malignancies, and their relative abundance in clinical cancer specimens has been correlated with malignant disease progression in human patients. Furthermore, recent findings suggest that clinical cancer progression driven by CSCs may contribute to the failure of existing therapies to consistently eradicate malignant tumors. Therefore, CSC-directed therapeutic approaches might represent translationally relevant strategies to improve clinical cancer therapy, in particular for those malignancies that are currently refractory to conventional anticancer agents directed predominantly at tumor bulk populations.