There are 5 clinical trials
This study is a single arm, pilot study of sirolimus in patient with Phosphatidylinositide-3-kinase (PIK3CA) mutation, PIK3CA amplification , PIK3CA-AKT pathway aberration Refractory solid tumor and/or specific sensitivity to mTOR inhibitors by Avatar scan that has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy. sirolimus 1mg will be administered orally daily. To investigate the efficacy and safety of sirolimus in patient with Refractory solid tumor.
- Patients must be >= 19 years of age - Phosphatidylinositide-3-kinase (PIK3CA) mutation, PIK3CA amplification , PIK3CA-AKT pathway aberration( H1047R, E542K, E545K, PTEN LOSS) Refractory solid tumor and/or specific sensitivity to mTOR inhibitors by Avatar scan that has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy. --- H1047R --- --- E542K ---
In people whos cancers have a PIK3CA mutation, this trial will be evaluating the drug BKM120 as a possible treatment. BKM120 works by blocking the phosphatidylinositol-3-kinase (PI3K)pathway, thereby inhibiting tumor growth and survival. The purpose of this study is to learn if the study drug BKM120 can shrink or slow the growth of your tumor. The safety of BKM120 will also be studied. Your physical state, symptoms, change in the size of your tumor, and laboratory findings obtained while you are on study will help the research team decide if BKM120 is safe and effective in patients with advanced cancers.
Inclusion Criteria: - At least 1 site of measurable disease - Life expectancy >/= 12 weeks - Adequate marrow and organ function - Diagnosis of lung cancer, breast cancer, colorectal cancer, cholangiocarcinoma, gastric cancer, pancreatic cancer, prostate cancer, uterine cancer, ovarian cancer, esophageal cancer, or head and neck cancer - Pathologically documented, definitively diagnosed, advanced solid tuor that is refractory to standard treatment, for which no standard therapy is available, or the subject refuses standard therapy - Cancer must have at least one of the following PIK3CA mutations: E542K, E545K, H1047R, H1047L. --- E542K ---
The PIK3CA mutation must be documented in a CLIA approved laboratory Exclusion Criteria: - Prior treatment with a P13K inhibitor - Known hypersensitivity to BKM120 or its excipients - Untreated brain metastases - Acute or chronic liver, renal disease or pancreatitis - Currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A - Diarrhea >/= CTCAE grade 2 - Any concurrent severe and/or uncontrolled medical condition - Active cardiac disease - History of cardiac dysfunction - Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus - Significant symptomatic deterioration of lung function - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKDM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) - Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant - Pregnant or breast-feeding - Known diagnosis of HIV infection - History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix - Unable to swallow the medication in its prescribed form Inclusion Criteria: - At least 1 site of measurable disease - Life expectancy >/= 12 weeks - Adequate marrow and organ function - Diagnosis of lung cancer, breast cancer, colorectal cancer, cholangiocarcinoma, gastric cancer, pancreatic cancer, prostate cancer, uterine cancer, ovarian cancer, esophageal cancer, or head and neck cancer - Pathologically documented, definitively diagnosed, advanced solid tuor that is refractory to standard treatment, for which no standard therapy is available, or the subject refuses standard therapy - Cancer must have at least one of the following PIK3CA mutations: E542K, E545K, H1047R, H1047L. --- P13K --- --- E542K ---
Description: Objective Response Rate (CR or PR) by RECIST 1.1 criteria
Measure: Response Rate Time: 2 yearsDescription: Clinical Benefit Rate (CR, PR, or SD) by RECIST 1.1 criteria
Measure: Clinical Benefit Rate Time: 2 yearsDescription: Progression Free Survival (PFS)
Measure: Survival Time: 2 yearsDescription: Determine if the presence of specific co-existing mutations may influence clinical benefit from BKM120
Measure: Clinical Benefit Time: 2 yearsThis phase II trial studies how well copanlisib works in treating patients with endometrial cancer that has not decreased or disappeared, and the cancer may still be in the body despite treatment (persistent) or has come back (recurrent). Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Associations between mutation subtypes and clinical outcomes will be explored using standard statistical methods for categorical and time to event data.. Inclusion Criteria: - Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up - Women of child-bearing potential (WOCBP) must agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug - Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial - Patients must have recurrent or persistent endometrial cancer (endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation of the primary tumor is required - All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patients must have at least one ?target --- R88Q --- --- N345K --- --- C420R --- --- E542K ---
lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy); there is no delay required for minor procedures (e.g., tumor fine-needle aspiration [FNA] or core biopsy, venous access device placement) - Patients may have received prior radiation therapy for treatment of endometrial cancer; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy; all radiation therapy must be completed at least 4 weeks prior to registration - Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration - Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration - Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but not required to receive, up to a total of 3 lines of chemotherapy - Appropriate stage for study entry based on the following diagnostic workup: - History/physical examination within 28 days prior to registration - Imaging of target lesion(s) within 28 days prior to registration - Completion of pre-study protocol specific assessments as required - Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2 within 28 days prior to registration - Absolute neutrophil count (ANC) >= 1,500/mcl - Platelets >= 75,000/mcl - Hemoglobin (Hgb) >= 8 g/dL - Creatinine =< 1.5 x upper limit of normal (ULN) - Bilirubin =< 1.5 x ULN (=< 3 x ULN for patients with Gilbert syndrome) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN - Left ventricular ejection fraction (LVEF) >= 50% - Fasting cholesterol less than or equal to 300 mg/dl; fasting triglycerides less than or equal to 300 mg/dl - Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of normal - The patient must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information - Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry - Patients with hypertension on medical management must have systolic blood pressure < 150 mmHG or diastolic pressure < 90 mmHG at study entry - Note: ULN is institutional or laboratory upper limit of normal - Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy Exclusion Criteria: - Patients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitor - Patients who have the following histologies: mucinous, squamous, sarcomas, carcinosarcomas, clear cell - Congestive heart failure > New York Heart Association (NYHA) class II - Myocardial infarction or unstable angina less than 6 months before registration - Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration - Non-healing wound, ulcer or bone fracture - Active, clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 - History of, or current autoimmune disease - Human immunodeficiency virus (HIV) infection - Hepatitis B (HBV) or hepatitis C (HCV); all patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel; patients with active HBV or hepatitis C infection are not eligible for enrollment; patients with serologic markers of HBV immunization due to known vaccination (hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B core [HBc] negative and anti-hepatitis B surface [HBs] positive) will be eligible - Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated: - Cervical carcinoma in situ - Non-melanoma skin cancer - Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) - Patients with seizure disorder requiring medication - Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration - Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h - History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) - Concurrent diagnosis of pheochromocytoma - Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure, excluding alopecia - Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation - Strong CYP3A4 inhibitors and inducers; concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within two weeks prior to start of study treatment and for the duration of treatment with copanlisib - Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study - Anti-arrhythmic therapy other than beta blockers or digoxin - Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed; patients may be using topical or inhaled corticosteroids - Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies - Concomitant radiotherapy - Women who are breast feeding Inclusion Criteria: - Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up - Women of child-bearing potential (WOCBP) must agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug - Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial - Patients must have recurrent or persistent endometrial cancer (endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation of the primary tumor is required - All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patients must have at least one ?target --- R88Q --- --- N345K --- --- C420R --- --- E542K ---
Description: Confirmation of complete and partial responses in tumor evaluations at least 4 weeks apart is required. Exact 95% confidence limits, accounting for the interim analysis, will be provided.
Measure: Frequency of objective response defined by RECIST 1.1 criteria Time: Up to 5 yearsDescription: Will be estimated using Kaplan-Meier product limit estimates.
Measure: PFS defined using RECIST 1.1 criteria Time: Duration of time from study entry to time of progression or death, whichever occurs first, or date of last contact, assessed at 6 monthsDescription: Will be estimated using Kaplan-Meier product limit estimates.
Measure: Median PFS using RECIST 1.1 criteria Time: Duration of time from study entry to time of progression or death, whichever occurs first, or date of last contact, assessed up to 5 yearsDescription: Will be estimated using Kaplan-Meier product limit estimates.
Measure: OS Time: Duration of time from study entry to time of death or the date of last contact, assessed up to 5 yearsDescription: Frequencies of maximum grade of adverse events by term or category will be reported. Grade 5 adverse events will be individually reported.
Measure: Incidence of adverse events of copanlisib using CTCAE version 4.03 Time: Up to 5 yearsDescription: Associations between mutation subtypes and clinical outcomes will be explored using standard statistical methods for categorical and time to event data.
Measure: Mutation subtypes and clinical outcomes Time: Up to 5 yearsRATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving cisplatin and paclitaxel together with everolimus may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin and paclitaxel together with everolimus and to see how well it works in treating patients with metastatic breast cancer.
- To screen for exon 9 (E542K and E545K), exon 20 (H1047R), and phosphatidylinositol 3-kinase (PI3K) (p110α) mutations in DNA extracted from paraffin blocks. --- E542K ---
Description: The recommended dose for the Phase II trial will be the most prevalent dose delivered per week in Phase I that allows for safe and feasible administration of the medications.The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy.
Measure: Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer Time: at 8 weeksDescription: The recommended dose for the Phase II trial will be the most prevalent dose delivered per day in Phase I that allows for safe and feasible administration the medication. The MTD is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy
Measure: Maximum Feasible Dose in mg of RAD001 (Everolimus)for Women With Metastatic Breast Cancer Time: at 8 weeksDescription: Patients who had not experienced disease progression and who were alive at 6 months after study entry
Measure: Patients With Progression-free Survival Time: at 6 monthsDescription: Per Response Evaluation Criteria in Solid Tumor (RECIST) criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
Measure: Patients With Overall Response Time: every 12 weeksDescription: Duration in months from date on-study to date patient exhibited progressive disease
Measure: Time to Progression Time: Up to 64 weeksDescription: Median duration in months from on-study to disease progression in patients with metastatic basal-like breast cancer. All patients with basal-like breast cancer are negative for estrogen, progesterone, and human epidermal growth factor (HER2) receptors.
Measure: Time to Progression in Patients With Metastatic Basal-like Breast Cancer. Time: Up to 64 weeksRATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole +/- goserelin (the latter for pre-menopausal women only) may fight breast cancer by lowering the amount of estrogen the body makes. OSI-906 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether hormone therapy and OSI-906 are more effective when given with or without erlotinib hydrochloride in treating hormone-sensitive metastatic breast cancer. PURPOSE: This phase II trial is studying how well giving hormone therapy together with OSI-906 with or without erlotinib hydrochloride works in treating hormone-sensitive patients with metastatic breast cancer.
Mutation analysis of PI3K (E542K, E545K, H1047R). --- E542K ---
- To correlate the mutational status of PI3K (E542K, E545K, H1047R) in DNA extracted from FFPB or fresh biopsy with clinical outcome and luminal A vs. luminal B subtypes of breast cancer OUTLINE: This is a multicenter study. --- E542K ---
Description: Duration from study enrollment to date of progressive disease (PD) as measured by Response Evaluation in Solid Tumors (RECIST) criteria v. 1.1: measurable lesions: PD is > 20% increase in the sum of the longest diameter of target lesions or appearance of new lesions
Measure: Time to progression Time: from study entry to date of progressive diseaseDescription: The number of patients with worst-grade toxicity at each of five grades following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death
Measure: Safety profile of OSI-906 and letrozole +/ goserelin, with and without erlotinib Time: at 4 weeksDescription: Per RECIST criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
Measure: Response Time: every 12 weeks to progressionDescription: Levels of the protein C-peptide and the hormone IGF-1 in the blood
Measure: Circulating C-peptide, IGF-1 Time: At baseline and on day 1 of each 28-day cycleDescription: The levels of these biomarkers will be measured in breast tumor tissue and compared and contrasted with patient's time to progression and molecular classification (luminal A vs. luminal B)
Measure: Correlation of IGF-IR, EGFR, HER2, Y1316 and Y1131 pIGF-1R, PTEN, S473 pAkt, pMAPK, S118 (MAPK site), and S167 (Akt and S6 site) pER expression with time to progression and molecular classification Time: On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgeryDescription: Breast tumor tissue will be examined for mutations in these genes.
Measure: Mutation analysis of PI3K (E542K, E545K, H1047R) Time: On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgery