View clinical trials related to Advanced Breast Cancer.
Filter by:This is a single-arm, open-label, phase Ib study. In this trial, patients with Triple Negative (TN) Advanced Breast Cancer (ABC) will be treated with increasing doses of LDE225 (sonidegib) and docetaxel to determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D) of the combination. Eligible patients with hormonal receptors negative and Human Epidermal Growth Factor Receptor 2 (HER2) negative ABC will be included and treated with docetaxel intravenously in every three weeks cycles. LDE225 will be administered orally at three dose levels 400, 600 and 800mg one a day (QD) (a -1 dose level is included just in case dose de-escalation is needed). Treatment will be repeated on day 1 of a 21-day cycle until radiographic or symptomatic progression, unacceptable toxicity or withdraws informed consent. The investigators propose to develop a phase Ib trial with the combination of docetaxel with LDE225 in TN ABC patients to define the safety, tolerability and RP2D, as well as to have some information about the efficacy of the combination.
Background: - The poly (ADP-ribose) polymerase (PARP) family of enzymes is critical for maintaining genomic stability by regulating a variety of deoxyribonucleic acid (DNA) damage repair mechanisms. - Talazoparib (BMN 673) is a PARP inhibitor with greater in vitro activity than any other PARP inhibitor currently in development. BMN 673 has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines and has potent antitumor activity in animal models of tumors harboring mutations in DNA repair pathways. - BMN 673 is showing promising single-agent activity in patients with advanced ovarian and breast cancer harboring deleterious BRCA mutations. - This pilot study will evaluate the pharmacodynamic effects of BMN 673 on DNA damage and apoptosis markers in tumor biopsy tissue. Primary Objective: -Determine the pharmacodynamic effect of BMN 673 in tumor biopsies from patients with advanced ovarian, breast, or other solid tumor and deleterious BRCA mutations. Secondary Objectives: - Determine the response rate (Complete Response (CR) + Partial Response (PR) of treatment with BMN 673 in patients with advanced ovarian or primary peritoneal carcinoma and deleterious BRCA mutations. - Determine the response rate (CR + PR) of treatment with BMN 673 in patients with advanced breast carcinoma and deleterious BRCA mutations. - Determine the response rate (CR + PR) of treatment with BMN 673 in patients with advanced solid tumor (other than breast or ovarian) and deleterious BRCA mutations. Eligibility: - Adult patients with documented deleterious BRCA 1 or 2 mutations with histologically confirmed ovarian, primary peritoneal, breast, prostate, pancreas, gastric or other solid tumor whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options. - No major surgery, radiation, or chemotherapy within 4 weeks prior to study enrollment, and recovered from toxicities of prior therapies to at least eligibility levels. - Age greater than or equal to 18 years of age; Eastern Cooperative Oncology Group (ECOG) performance status less than equal to 2 - Adequate organ function. - Willingness to undergo tumor biopsies. Study Design: - BMN 673 will be administered orally each day in 28-day cycles. - Dosing will be at the established recommended Phase II dose of 1000 mcg/day each day for 28 days. - We plan to accrue a total of 12 evaluable patients per cohort for a total of 36 patients. To allow for some patients who will not be evaluable, the accrual ceiling is 42 patients. - Tumor biopsies will be mandatory at baseline (pre-dose), and then approximately 3-6 hours post BMN 673 on day 8. An optional tumor biopsy may also be collected at time of disease progression. SCHEMA - BMN 673 is administered orally each day in 28-day cycles - Tumor biopsies will be performed at baseline (pre-treatment) and 3-6 hrs post dose on cycle 1 day 8. An optional tumor biopsy may also be collected at time of disease progression. Tumor biopsies will be evaluated for protease activated receptor (PAR) levels, DNA damage response markers such as >=H2A.X Variant Histone (H2AX), cleaved caspase 3, excision repair cross-complementing group 1 (ERCC1), pNbs1, XPF, RAD51, and pT1989ATR, and, as indicators of ataxia telangiectasia and Rad3-related protein (ATR)/ataxia telangiectasia mutated (ATM) activation, Checkpoint kinase 1 (chk1) and Checkpoint kinase 2 (chk2) - Blood samples for circulating tumor cells (CTC) analyses will be collected at baseline (pre-treatment), on cycle 1 day 1(3-6 hours post dose), on cycle 1 day 8 (3-6 hours post dose), and on cycle 2 day 1 (3-6 hours post dose) - Blood samples for pharmacokinetic (PK) analysis will be collected on cycle 1 day 1 pre-dose and 0.5, 1, 2, 3, 4, 6,8, and 24 hours post-dose, on cycle 1 day 8 (3-6 hours post dose), and on cycle 2 day 1 pre-dose and 3-6 hours post dose.
Standard of care: Treatment with Trastuzumab Experimental: 21-Day Cycle of Combination therapy with T-DM1 intravenously on Day 1 and oral PD-0332991 on Days 5-18 Study Design and Methodology: This is a phase 1B inter-patient dose escalation study of PD-0332991 in combination with T-DM1 in patients with recurrent or metastatic HER2-positive breast cancer after prior trastuzumab or other HER2-directed therapies. The subjects will be administered T-DM1 by intravenous infusion at 3.6 mg/kg for 90 minutes on day 1 of each 21 day cycle. Infusion timing may vary from 30-90 minutes depending on how well the subject tolerates the treatment. A standard 3+3 trial design will be used for PD-0332991 dose escalation cohorts.The dosing of PD-0332991 will be divided into 3 cohorts, the subjects will receive PD-0332991 on days 5-18 of each 21 day cycle. Cohort 1 : PD-0332991 - 100 mg daily (oral) Cohort 2 : PD-0332991 - 150 mg daily (oral) Cohort 3 : PD-0332991 - 200 mg daily (oral) The 3+3 design entails that if one patient out of the first three patients has a DLT, up to three additional patients will be entered at that dose level Treatment cycles will continue until disease progression or withdrawal from study.
Brief Description: This study is designed to evaluate the safety and tolerability of oral Selatinib Ditosilate Tablets, and explore the maximum tolerated dose (MTD) and dose-limiting toxicity in patients with advanced breast cancer.
This research study will examine how patients with advanced breast cancer and their oncology team communicate and plan ongoing care.The purpose of this study is to find out more about care planning during advanced breast cancer. The study will see if certain aspects of communication make a difference in how patients understand their illness.
There are three major subtypes of breast cancer: 1. Hormone receptor positive (contain cells that express the estrogen receptor or progesterone receptor). 2. Tumors that express the epidermal growth factor receptor gene ( HER-2) 3. Triple negative (cancer cells that lack the hormone receptors and the epidermal growth factor receptor gene HER-2. While effective therapies exist for most cases of breast cancer at first occurrence, many patients eventually exhibit disease that does not respond to all standard breast therapies, particularly in the metastatic setting. There are therapies that are used to treat other types of cancers with genetic mutations that are in the process of being evaluated for use in breast cancer. The current techniques used for detecting mutations in the genes of breast cancer patients, which can be treated with drugs specific for the genetic mutations, are invasive and identifying effective diagnostic non-invasive procedures are the next challenge for physicians. This study will compare the ability to detect genetic mutations samples from non-invasive procedures such as a blood draw, to more invasive procedures such as tissue taken from a biopsy sample. There is also a concern with current techniques used to detect genetic mutations that cells from a single tissue sample may not be representative of the types of cells present in all the tumors in the body and therapies selected using a single tissue sample may not be effective for all of the cancer in the body. This study will use blood drawn from participants prior to any drug therapy and compare the genes from this blood to tissue samples from multiple sites of disease. The study will also compare the genetic profile of the metastatic tumors to the genetic profile of the original breast cancer to determine if there are any changes in the genetics of the tumor cells. The participants that have newly diagnosed metastatic disease will provide tissue from their primary site of disease via an image guided biopsy. These participants will also provide tissue from at least 2 other distant metastatic sites (lung, pleural/peritoneal, liver, brain, or skin). Each biopsy procedure will attempt to obtain 2-3 samples for research purposes. Participants that have locally recurrent disease in the breast will have the tissue from the site of re-occurrence biopsied as well as two distant metastatic sites (lung, pleural/peritoneal, liver, brain, or skin). Participants that have either multi-centric disease or bilateral disease will have all tumors sampled with the intention of providing 2-3 samples/tumor for research purposes. Participants with multi-centric and bilateral disease will also have 2 distant sites of distant disease sampled (lung, pleural/peritoneal, liver, brain, or skin). Prior to any scheduled biopsy procedures all participants will have a blood draw used to examine the genetics of the tumor cells in the blood. The participants will have 8 tubes of blood drawn for the test and then they will proceed onto the tissue sampling portion of the study.
The Combination of GnRh Analogue and Aromatase Inhibitor in Receptor Positive Premenopausal Women with Advanced Breast Cancer A Prospective Trial.
This study is a multicentre, open label, non-randomized phase I study. The main objectives of the study are to determine the pharmacokinetic profile of the drug at different dose levels in the patients with Advanced Breast Cancer. Maximum Tolerated Dose (MTD) and safety of Paclitaxel Nanoparticle will also be simultaneously assessed.
Primary objective of the study is to evaluate the correlation between level of HER2-neu gene amplification evalued by dual-color Fluorescent in-situ hybridization (FISH) test and time to progression (TTP) in patients with HER2-positive advanced breast cancer treated with trastuzumab-containing regimens.
This is a phase 2, open-label, multicenter, 2-arm study of bosutinib administered in combination with exemestane versus exemestane alone. This is a 2-part study consisting of a safety lead-in phase and randomized phase 2 portion. Subjects in part 1 will receive bosutinib and exemestane daily, and will be closely monitored for 28 days. If no safety concerns arise, then future eligible subjects will be randomly assigned to the main phase of the study. They will either receive bosutinib daily combined with daily exemestane, or daily exemestane alone for a specified period of time. Subjects will be followed up for survival after treatment discontinuation.