Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

TAS0612

Taiho Oncology, INC

Erika Hamilton

Funda Meric-Bernstam

Capucine Baldini

The purpose of this study is to see if TAS0612 is safe in participants with advanced or metastatic solid tumor cancer.

A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer

A Phase 1 Study of TAS0612 in Patients With Locally Advanced or Metastatic Solid Tumors

Structure elucidation of TAS0612 metabolites in human plasma.

To explore the correlation between the incidence of exposures of TAS0612 in plasma and QT prolongation

To investigate potential predictive biomarkers for TAS0612.

To explore the correlation between PK and antitumor activity or toxicity

Number of participants with DLTs during cycle 1

Percentage of participants with partial response (PR) or complete response (CR) at 6 months Prostate Cancer Working Group 3 (PCWG3)/ modified defined by the Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1.

DCR: Percentage of participants who exhibit stable disease (SD), PR or CR.

DOR: Date of PR or CR to date of objective progression or death due to any cause.

Proportion of patients experiencing a radiographic progression by PCWG3/mRECIST1.1 criteria

Proportion of patients experiencing a best overall response of Complete Response (CR) or Partial response (PR)

Proportion of patients with ≥50% reduction in PSA from baseline to lowest post-baseline result.

Area under the plasma concentration curve of TAS0612.

time it takes for plasma concentration to fall by half its original value (t1/2) of TAS0612

Total proteins will be measured in blood samples collected at different time points.

Phospho-proteins will be measured in blood samples collected at different time points. The levels/changes (dose- and concentration-dependent) of phospho-proteins will be assessed and reported for biochemical effects of TAS0612.

Selected phospho-proteins will be analyzed in tumor tissue at baseline and on-treatment in dose escalation. The levels/changes of the phospho-proteins will be assessed and reported for target modulation.

Taiho Oncology, Inc.

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Double-blinded, Randomized in a 1:1 ratio in Study Parts A and B2 Single arm Open label in Study Part B1

Double-blinded, Randomized in a 1:1 ratio in Study Parts A and B2 Not applicable in Study Part B1

alpelisib

placebo

100 mg/m² as IV infusion on Days 1, 8 and 15 of a 28-day cycle

nab-paclitaxel

Novartis Pharmaceuticals

The purpose of this study is to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in subjects with advanced triple negative breast cancer (aTNBC) who carry either a PIK3CA mutation (Study Part A) or have PTEN loss (Study Part B1) or PTEN loss without PIK3CA mutation (Study Part B2)

The recruitment of Part A was halted on 11-Nov-2022 due to slow recruitment. Since Part B1 did not meet its primary objective for confirmed overall response rate the Part B2 will not be initiated and the recruitment was halted for the entire study

Study Assessing the Efficacy and Safety of Alpelisib + Nab-paclitaxel in Subjects With Advanced TNBC Who Carry Either a PIK3CA Mutation or Have PTEN Loss

A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Nab-paclitaxel in Patients With Advanced Triple Negative Breast Cancer With Either Phosphoinositide-3-kinase Catalytic Subunit Alpha (PIK3CA) Mutation or Phosphatase and Tensin Homolog Protein (PTEN) Loss Without PIK3CA Mutation

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

PFS, defined as time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST 1.1

ORR is defined as the proportion of subjects with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1

OS is defined as the time from date of randomization to date of death due to any cause

ORR with confirmed response is the proportion of subjects with BOR of confirmed complete response (CR) or confirmed partial response (PR), as per local review and according to RECIST 1.1

Clinical benefit rate (CBR) with confirmed response is defined as the proportion of subjects with a best overall response of confirmed complete response (CR), or confirmed partial response (PR), or an overall response of stable disease (SD) lasting for a duration of at least 24 weeks. CR, PR, and SD are defined as per local review according to RECIST 1.1

Time to response (TTR) is defined as the time from the date of randomization/enrolment to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed (although date of initial response is used, not date of confirmation). CR and PR are based on tumor response data as per local review and according to RECIST 1.1

Duration of response (DOR) with confirmed response only applies to subjects whose best overall response is confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date is the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying cancer

OS is defined as the time from date of enrolment to date of death due to any cause

PFS, defined as time from the date of enrolment to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST 1.1

Summary statistics of plasma alpelisib concentrations by time point

Summary of composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment

Definitive deterioration: time from date of randomization to date of event, defined as at least a 10% worsening from baseline with no later improvement above this threshold observed during the course of the treatment or until death due to any cause, in the global health status/QOL scale score of EORTC QLQ-C30, a questionnaire to assess the quality of life of cancer patients. The questionnaire contains 30 items \& is composed of both multi-item scales \& single-item measures based on the patient's experience over the past week. This includes 5 functional scales, 3 symptom scales, 6 single items \& a global health status/QoL scale. The scales \& single-item measures range in score from 0 - 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning; a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems

PFS in patients with PIK3CA mutation as measured in ctDNA

Definitive deterioration of ECOG PS is defined as the time from the date of randomization to the date of event defined as a worsening of at least once category from baseline in ECOG PS with no later improvement above this threshold observed during the course of the treatment or until death due to any cause

Rare Diseases

Sarcoma

Osteosarcoma

Sarcoma, Ewing

Chondrosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

3+3 design for phase I for RP2D (Recommended Phase 2 Dose) for adolescents (12-17 years old) (15mg QD or 20mg QD); phase II for efficacy exploration for another 17 patients using RP2D QD

TQB3525 is an orally bioavailable, potent, class I kinase inhibitors of PI3Ka and PI3Kd.

TQB3525

Wei Guo, Ph.D and M.D.

The PI3K, protein kinase B (AKT), and mTOR signaling network promotes cell growth, survival, metabolism, and motility, but becomes a critical oncogenic driver under aberrant conditions that control the tumor microenvironment and angiogenesis. The PI3K-AKT-mTOR axis is the most frequently deregulated signaling pathway in primary osteosarcoma and other bone tumors. PI3Ka has high rates of 25-50% activating mutations associated with tumor formation in osteosarcoma. Other causes of pathway hyperactivation include loss of function of the tumor suppressor PTEN, gain-of-function mutations in AKT and PDK1, or upregulation of receptor tyrosine kinases. TQB3525 is an orally bioavailable, potent, dual catalytic site inhibitor of PI3Ka and PI3Kd. Tumor growth inhibition has been demonstrated in multiple xenograft osteosarcoma models with PI3K-mutant, PTEN-null cell lines. The investigators try to investigate TQB3525 in primary osteosarcoma and other bone tumors for its safety, tolerability, dose-limiting toxicities (DLT), MTD and antitumor efficacy.

TQB3525 for Advanced Bone Sarcomas With PI3KA Mutations or PTEN Loss

Phase I Study of TQB3525, Phosphatidylinositol-3-Kinase α and δ Inhibitors, in Patients With Advanced Bone Sarcomas

from starting treatment to progression/death

Peking University People's Hospital

Director, Head of Msculoskeletal Tumor Center

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Androgens

Ipatasertib

Hormones

Hormone Antagonists

Protein Kinase Inhibitors

Enzyme Inhibitors

Cycle 0 Days 1-7: Ipatasertib Monotherapy + Androgen Deprivation Therapy (ADT) Cycle 1+: Ipatasertib + Darolutamid + ADT

All Cycles: Ipatasertib + Darolutamide + ADT

Darolutamide

Androgen Deprivation Therapy

David VanderWeele, MD\Phd

This multicenter Phase I/II trial consists of two stages: a phase I stage in patients with castration resistant prostate cancer in which the recommended phase II dose will be determined for ipatasertib administered in combination with darolutamide; and a phase II neoadjuvant stage in which patients with high risk prostate cancer and loss of PI3K pathway activation in the tumor tissue planning on undergoing prostatectomy receive ADT, darolutamide, and ipatasertib for 24 weeks prior to planned surgery.

The proposed trial is a single arm, two stage trial looking for an efficacy signal in the neoadjuvant setting in patients with PTEN-null tumors. The active therapy is a combination of androgen deprivation therapy, darolutamide, and ipatasertib. Patients will be treated for 6 months prior to prostatectomy, since previous studies have shown that pCR+MRD rate is higher with 6 months of ADT + abiraterone (24%) than 3 months (4%) (Taplan ME et al. J Clin Oncol. 2014;32(33):3705-15). Since the combination has not been evaluated before, a lead-in cohort in patients with castration resistant prostate cancer will be performed to evaluate safety and drug-drug interaction.

The lead-in cohort will enroll 6 patients to assess the safety of ipatasertib and darolutamide. Ipatasertib has already been evaluated in combination with the AR pathway inhibitors abiraterone and enzalutamide, where 400 mg was found to be safe. Therefore patients will receive the expected final dose of darolutamide 600 mg BID and ipatasertib 400 mg daily. Toxicities will be monitored for 28 days, and blood samples will be drawn for pharmacokinetic (PK) studies. If one or fewer patients experience a DLT the trial will advance to the neoadjuvant setting. If two or more patients experience a DLT at 400 mg, the dose will be reduced for already enrolled patients and another 6 patients will be enrolled to evaluate darolutamide 600 mg BID and ipatasertib 200 mg daily.

PK evaluations will continue for a total of 6 months. Enrollment in the neoadjuvant cohort can proceed before PK studies are complete.

Patients in the Phase I portion will have response evaluated at 12 weeks, including PSA response and radiographic response per modified PCWG3. If there is progression on bone scan alone, patients should have confirmatory bone scan at least 6 weeks later. Patients will continue on therapy until the time of progression.

Subject's must be biologically male to participate in this study

Neoadjuvant Androgen Deprivation, Darolutamide, and Ipatasertib in Men With Localized, High Risk Prostate Cancer

A Single Arm, Phase I/II Trial of Neoadjuvant Androgen Deprivation, Darolutamide, and Ipatasertib in Men With Localized, High Risk Prostate Cancer Big Ten Cancer Research Consortium BTCRC-GU19-404

Combined rate of pathologic complete response (pCR) (defined as absence of pathologic disease on hematoxylin and eosin (H\&E) stain (ypT0)), or with presence of minimal residual disease (\<5 mm linearly)

A summary of all dose-limiting toxicities experienced by Phase I subjects within the first cycle (28 days) of treatment, as defined in the study protocol.

Two year biochemical recurrence-free survival (PSA ≤ 0.2 ng/mL) will be measured in men with high risk, localized, prostate cancer that is lacking PTEN

Rate of PSA0 (undetectable PSA on local institutions laboratory testing with testosterone recovery and no additional therapy) will be measured in men with high risk, localized, prostate cancer that is lacking PTEN.

David VanderWeele

Associate Professor, Medicine - Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Adverse events were recorded from the time of consent for at least 30 days after treatment discontinuation or until a new anti-cancer treatment starts, whichever occurs first, per Common Terminology Criteria for Adverse Events (CTCAE) v5.

Cycle 0 Days 1-7: Ipatasertib Monotherapy + Androgen Deprivation Therapy (ADT)

Cycle 1 Day 1+: Ipatasertib 400 mg daily (AM dose with PKs)+ Darolutamide 600 mg BID (No AM dose.PM dose taken after ipatasertib monotherapy PKs)+ ADT (per institutional standards)

Phase I De-Escalation Cohort, Level 1: Ipatasertib 400 mg Daily + Darolutamide 600 mg BID + ADT

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

A 5 Grade Group System was created to have a better way to describe how a cancer will behave and respond to treatment.

Grade group 1: Gleason score 6 or lower (low-grade cancer) Grade group 2: Gleason score 3 + 4 = 7 (medium-grade cancer) Grade group 3: Gleason score 4 + 3 = 7 (medium-grade cancer) Grade group 4: Gleason score 8 (high-grade cancer) Grade group 5: Gleason score 9 to 10 (high-grade cancer)

Gleason score

Tumor Location

Annesha Majumdar

All Cycles: Ipatasertib + Darolutamide + ADT

Ipatasertib: Ipatasertib were planned to be administered orally per Phase I cohort determined dose of 400mg daily for each cycle length of 28 days

Darolutamide: Darolutamide were planned to be administered orally at a dose of 600mg BID for each cycle length of 28 days

Androgen Deprivation Therapy: ADT per institutional standards

Phase II Neoadjuvant Cohort,MTD: Ipatasertib 400 mg + Darolutamide 600 mg BID + ADT

Study was terminated after the completion of Phase I accrual. No data for this cancelled Phase II objective was collected or analyzed as no prostatectomies were performed in any subject (a pre-requisite for determining pCR).

Phase II: Pathological Complete Response (pCR) Rate

All Cycles: Ipatasertib 400mg + Darolutamide 600mg BID + ADT per institutional guidelines

Phase I De-Escalation Cohort

Six Phase I subjects are included in the analysis population.

Summary of Dose-Limiting Toxicities

Study was terminated after the completion of Phase I accrual. No Phase II subjects were accrued, and no data for this cancelled Phase II objective were collected or analyzed. Additionally, no subjects from the Phase I study were followed for sufficient time to collect two-year biochemical recurrence-free survival, as they did not consent for this activity.

Phase II - Two Year Biochemical Recurrence-free Survival

Study was terminated after the completion of Phase I accrual. No Phase II subjects were accrued, treated, or evaluated for this objective, and no data for this cancelled Phase II objective was collected or analyzed. This analysis was planned in only Phase II subjects.

Phase II: Rate of PSA0

Cycle 0 Days 1-7: Ipatasertib Monotherapy + Androgen Deprivation Therapy (ADT)

Cycle 1 Day 1+: Ipatasertib 200 mg daily (AM dose with PKs)+ Darolutamide 600 mg BID (No AM dose.PM dose taken after ipatasertib monotherapy PKs)+ ADT (per institutional standards)

Phase I De-Escalation Cohort, Level -2: Ipatasertib 200 mg Daily + Darolutamide 600 mg BID + ADT

Cycle 0 Days 1-7: Ipatasertib Monotherapy + Androgen Deprivation Therapy (ADT)

Cycle 1 Day 1+: Ipatasertib 300 mg daily (AM dose with PKs)+ Darolutamide 600 mg BID (No AM dose.PM dose taken after ipatasertib monotherapy PKs)+ ADT (per institutional standards)

Phase I De-Escalation Cohort, Level -2: Ipatasertib 300 mg Daily + Darolutamide 600 mg BID + ADT

Study Treatment

Follow up

Blood and Lymph Conditions

Immune System Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Lymphoma

Lymphoma, Non-Hodgkin

Leukemia

Leukemia, Lymphoid

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Zhen zijun

Sun xiaofei

With the development of molecular biology and precise medical treatment, new challenges have been raised in the diagnosis and treatment of non-Hodgkin lymphoma (NHL) in children. In recent years, the criteria for clinical staging and efficacy evaluation of NHL in children have been updated. Recent clinical studies of COG in the United States and LMB in France have confirmed that molecular biological markers such as Notch1, PTEN and LOH6q are significantly associated with the prognosis of T-lymphoblastic lymphoma (T-LBL). These molecular biological markers should be included in the new risk stratification system. High-intensity treatment of high-risk patients will improve survival. Recent studies have also suggested that PET/CT is helpful in evaluating residual lesions in patients with lymphoma after chemotherapy. In order to keep pace with the times in the diagnosis, clinical staging, risk stratification, efficacy evaluation and treatment of NHL in children. SCCCG-LBL-2017 was formulated by South China Children's Cancer Group of Non-Hodgkin lymphoma, which mainly updated in clinical staging, efficacy evaluation, risk stratification, treatment,etc..

Research purpose:

1. To investigate the efficacy and safety of SCCCG-LBL-2017 in Chinese children with LBL.
2. To explore the feasibility of risk stratification of T-LBL by combining genotyping.
3. To investigate the correlation between MDD and MRD in lymphoblastic lymphoma and prognosis.
4. To investigate the role of PET/CT in the assessment of residual lymphoblastic lymphoma.
5. To explore the effect of reducing HD-MTX dosage and shortening maintenance therapy time on the efficacy and survival of low-risk LBL patients.
6. To explore the effect of prolonging the duration of maintenance therapy on the efficacy and survival of high-risk LBL patients.

A Prospective Multicenters Clinical Cohort Study of Stratified Treatment of Chinese Children With LBL

A Prospective Multicenter Cohort Study on the Efficacy and Safety of Stratified Treatment of Chinese Children With Lymphoblastic Lymphoma Based on Risk Factors

EFS is defined as time from start of treatment/randomization up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.

OS is defined as time from start of treatment/randomization up to death of any

RFS is defined as time from start of treatment/randomization up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease, or relapse.

Complete response, partial remission, objective effect, stable disease or progressive disease

Rate of patients with acute toxicity defined as grade III/IV/V AE

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer	NCT04586270	Advanced or Met...	TAS0612	18 Years -	Taiho Oncology, Inc.
Study Assessing the Efficacy and Safety of Alpelisib + Nab-paclitaxel in Subjects With Advanced TNBC Who Carry Either a PIK3CA Mutation or Have PTEN Loss	NCT04251533	Triple Negative...	alpelisib placebo nab-paclitaxel	18 Years -	Novartis
TQB3525 for Advanced Bone Sarcomas With PI3KA Mutations or PTEN Loss	NCT04690725	Safety Issues Efficacy, Self	TQB3525	12 Years -	Peking University People's Hospital
Neoadjuvant Androgen Deprivation, Darolutamide, and Ipatasertib in Men With Localized, High Risk Prostate Cancer	NCT04737109	Castrate Resist...	Ipatasertib Darolutamide Androgen Depriv...	18 Years -	Big Ten Cancer Research Consortium
A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer	NCT04586270	Advanced or Met...	TAS0612	18 Years -	Taiho Oncology, Inc.
Study Assessing the Efficacy and Safety of Alpelisib + Nab-paclitaxel in Subjects With Advanced TNBC Who Carry Either a PIK3CA Mutation or Have PTEN Loss	NCT04251533	Triple Negative...	alpelisib placebo nab-paclitaxel	18 Years -	Novartis
TQB3525 for Advanced Bone Sarcomas With PI3KA Mutations or PTEN Loss	NCT04690725	Safety Issues Efficacy, Self	TQB3525	12 Years -	Peking University People's Hospital
A Prospective Multicenters Clinical Cohort Study of Stratified Treatment of Chinese Children With LBL	NCT03971318	Lymphoma, Non-H... Lymphoblastic L... PTEN Loss NOTCH1 Gene Mut... Pediatric Cance...		1 Year - 18 Years	Sun Yat-sen University

Spots Global Cancer Trial Database for pten loss

Every month we try and update this database with for pten loss cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pten loss

Every month we try and update this database with for pten loss cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pten loss cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.