Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Anti-Bacterial Agents

Azacitidine

Antibiotics, Antitubercular

Antimetabolites

Enzyme Inhibitors

Azacitidine 75 mg/m\^2/day Subcutaneous for 7 days Day every 28 days for up to 6 cycles

Subjects will receive azacitidine 75 mg/m2/day SC for 7 days every 28 days for up to 6 cycles, unless they are discontinued from the treatment. In addition, subjects may receive best supportive care as needed, including antibiotics and transfusions, per Investigator discretion.

C L Beach, PharmD

The primary purpose of this study is to determine the effectiveness and safety of azacitidine in the treatment of Taiwanese subjects with higher-risk Myelodysplastic Syndrome (MDS).

The study has 3 phases which include the Screening Phase, the Treatment Phase, and the Post-Treatment Phase and outlined as follows:

Screening Phase:

Subjects will provide informed consent prior to undergoing any study-related procedures. Screening procedures are to take place within 28 days prior to the initiation of azacitidine treatment (Day 1, Cycle 1). Subject eligibility will be based on central pathology review. Bone marrow aspirate and bone marrow biopsy will be collected at screening and sent for morphological assessment by a central pathology reviewer prior to the subject receiving IP. The central pathology reviewer will document the MDS classification according to the FAB and WHO criteria (Appendix A and B, respectively).

A standard cytogenetic metaphase preparation will be prepared from the bone marrow aspirate and sent to the local or central laboratory (for sites without local analysis capability) for the cytogenetic analysis prior to receiving IP.

The IPSS score will be calculated using the central reviewer's pathology report for bone marrow blast percentage, local cytogenetic assessment for karyotype, and central laboratory report for number of cytopenias (Appendix D).

Treatment Phase:

The first dose of azacitidine for each subject begins on Day 1 of Cycle 1. All subjects will receive azacitidine 75 mg/m2/day SC for 7 days every 28 days for up to 6 cycles, unless they are discontinued from treatment. Visits during the treatment phase are to be scheduled weekly for the first 2 cycles, then every other week for all subsequent cycles throughout the rest of the study. Safety and efficacy measures are to be performed weekly, every other week, every 4 weeks, or at 24 weeks, depending on the procedure.

Post-Treatment Phase:

All discontinued subjects, regardless of reason for discontinuation, should undergo end-of-study procedures at the time of study discontinuation. Subjects will have a follow-up visit for the collection of adverse events up to 28 days after last IP dose.

Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)

A Phase 4, Open-Label, Single-Arm Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes.

A participant was considered transfusion dependent at baseline if the participant had one or more Red Blood Cell transfusions during the 56 days prior to first dose. During the study, a participant was considered transfusion independent during the on-treatment period if the participant had no transfusions during any 56 consecutive days or more (e.g., Day 1 through 56, Day 2 through 57, etc). Otherwise, they were considered transfusion dependent.

The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: RBC dependent at BL=32, RBC independent at BL=12)

A participant was considered RBC transfusion-independent at baseline if the participant had no RBC transfusions during the 56 days prior to first dose. During the study, a participant was considered transfusion independent during the on-treatment period if the participant had no RBC transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered transfusion dependent.

The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: RBC dependent at BL=32, RBC independent at BL=12)

A participant was considered platelet transfusion dependent at baseline if the participant had one or more platelet transfusions during the 56 days prior to first dose. During the study, a participant was considered platelet transfusion independent during the on-treatment period if the participant had no platelet transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered platelet transfusion dependent.

The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: platelet dependent at BL=18, platelet independent at BL=26)

A participant was considered platelet transfusion independent at baseline if the participant had no platelet transfusions during the 56 days prior to first dose. During the study, a participant was considered platelet transfusion independent during the on-treatment period if the participant had no platelet transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered platelet transfusion dependent.

The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: platelet dependent at BL=18, platelet independent at BL=26)

Hematologic Response according to the 2000 International Working Group (IWG) response criteria for MDS was based on the Investigators determination and defined as:

* Complete Response (CR): repeat bone marrow (BM) shows \<5% myeloblasts, and peripheral blood values lasting ≥ 2 months of hemoglobin (hgb) (\>110 g/L), neutrophils (≥1.5x10\^9/L), platelets (≥100x10\^9/L), blasts (0%) and no dysplasia
* Partial Response (PR): same as CR for peripheral blood: BM shows blasts decrease by ≥ 50% or a less advanced FAB classification from pretreatment
* Stable disease (SD): failure to achieve a PR, no evidence of progression for at least 2 months.
* Failure: death during treatment or disease progression
* Relapse After CR or PR: return to pretreatment BM blast percent or decrement of ≥ 50% from remission/response levels in granulocytes or platelets; or reduction in hgb by ≥20 g/L or transfusion dependence
* Disease Progression: change in blast levels
* Disease Transformation to AML

Hematologic improvements (HI) have 4 categories:

1. Erythroid response (HI-E): Major \>20g/L increase or transfusion independent. Minor- 10-20g/L increase or ≥50% decrease in transfusion requirements.
2. Platelet response (HI-P): Major absolute increase of ≥30x10\^9/L or platelet transfusion independence. Minor-≥50% increase.
3. Neutrophil response (HI-N): Major 100% increase or an absolute increase of \>0.5x10\^9/L. Minor-≥100% increase and absolute increase of \<0.5x10\^9/L
4. Progression or relapse after HI

Overall hematological improvement (HI) was defined as any type (major or minor) of improvement of HI-E, HI-P, or HI-N. Criteria: Pretreatment=hemoglobin \<100g/L or RBC transfusion-dependent, platelet count \<100x10\^9/L or platelet transfusion dependent, absolute neutrophil count \<1.5x10\^9/L. Sponsor's determination was derived using clinically relevant data.

Denominator for progression/relapse after HI included participants who had achieved HI.

The number of transfusions received 56 days prior to treatment and during study were standardized per 28 days and summarized by cycle for RBCs. The formula for standardizing per 28 days was: \[(# of transfusions in the measurement period / length of the measurement period (days)) x 28\], where the measurement period was either baseline or the relevant cycle length. For each participant the overall post-baseline average was calculated as the average of # of RBC transfusions per cycle.

The number of transfusions received 56 days prior to treatment and during study was standardized per 28 days and summarized by cycle for platelets. The formula for standardizing per 28 days was: \[(# of transfusions in the measurement period / length of the measurement period (days)) x 28\], where the measurement period was either baseline or the relevant cycle length. For each participant the overall post-baseline average was calculated as the average of # of platelet transfusions per cycle.

The on-treatment adverse event of infection requiring IV antibiotics, antifungals, or antivirals per 28 days/cycle. The overall post-baseline average is the average of number of infections requiring IV antibiotics or IV antiviral per 28 days/cycle. For each participant the overall post-baseline average was calculated as the average of # of infections requiring IV antibiotics or IV antiviral per 28 days per cycle.

An AE that resulted in any of the following outcomes was defined as a serious adverse event (SAE):

* Death;
* Life-threatening event;
* Any inpatient hospitalization or prolongation of existing hospitalization;
* Persistent or significant disability or incapacity;
* Congenital anomaly or birth defect;
* Any other important medical event.

The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. Treatment Emergent AEs (TEAE) were defined as AEs with an onset date on or after the first dose of study drug and within 28 days after the date of the last dose. In addition, any AE that occurred beyond this timeframe and that was assessed by the investigator as possibly related to study drug was considered a TEAE.

Area under the plasma concentration-time curve from time zero to infinity (AUC∞) following multiple doses of Azacitidine on Day 7; if possible, the area under the concentration-time curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity was calculated according to the following equation: AUC∞ = AUCt + (Ct/ λz ), where Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If % AUC extrapolated is ≥ 25%, AUC∞ was not reported.

Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear trapezoidal rule when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

The observed maximum plasma concentration obtained directly from the observed concentration versus time data.

Time to maximum observed plasma concentration obtained directly from the observed concentration versus time data.

The apparent terminal half-life was calculated according to the following equation t½ = 0.693/λz.

Apparent total plasma clearance (CL/F) of Azacitidine was calculated as Dose/AUC∞

Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz

Celgene

Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

FAB is a classification system for five (5) subtypes of myelodysplastic syndrome that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts or a monocytosis. Classification was made by the Local Reviewer.

Myelodysplastic Syndrome (MDS) French-American-British (FAB) Classification

The World Health Organization (WHO) classification recognizes eight subtypes of MDS that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts (i.e., erythroid precursors with iron deposits surrounding the nucleus), presence of a monocytosis or a deletion 5q.

World Health Organization (WHO) Classification

The international prognostic scoring system (IPSS) is a standard for risk assessment in primary myelodysplastic syndromes (MDS) that categorizes prognoses taking into account cytogenetics, cytopenias, blasts and blood counts. The IPSS prognostic subgroups consist of low-, intermediate-1-, intermediate-2-, and high-risk groups. The scale is 0-3.5 at 0.5 increments. Scores of 0=Low; 0.5-1.0=Int-1; 1.5-2.0=Int-2; 2.5-3.5=High risk which corresponds to poorer prognosis. The assessment was performed by the local investigator

International Prognostic Scoring System (IPSS)

The intention-to-treat (ITT) population was defined as all enrolled participants.

Anne McClain

Overall (CR+PR)

Overall (CR+PR+SD)

Complete Remission (CR)

Partial Remission (PR)

Stable Disease (SD)

Disease Progression (DP)

Transformation to AML

Failure

No Response Assessed

The intention-to-treat (ITT) population was defined as all enrolled participants

Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator

Any improvement

Hematologic Improvement-E (major)

Hematologic Improvement-E (minor)

Hematologic Improvement-P (major)

Hematologic Improvement-P (minor)

Hematologic Improvement-N (major)

Hematologic Improvement-N (minor)

Progression/relapse after HI

Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor

Baseline Dependent: On-Treatment Independent

Baseline Dependent; On-Treatment Dependent

The intent-to-treat (ITT) participants who were transfusion dependent

Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline

Baseline Independent; On-Treatment Independent

Baseline Independent; On-Treatment Dependent

The Intent to Treat (ITT) participants who were transfusion independent

Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline

Baseline (N = 44)

Overall Post-Baseline Average (N = 44)

overall Change from Baseline ( N = 44)

Cycle 1 ( N = 44)

Cycle 2

Cycle 3

Cycle 4

Cycle 5

Cycle 6

ITT Population- The intent-to-treat (ITT) population was defined as all enrolled participants.

Number of Red Blood Cell (RBC) Transfusions by Cycle

Baseline Dependent; On-Treatment Independent

The intent-to-treat (ITT) population who were transfusion dependent

Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline

Baseline Independent: On-Treatment Independent

The intent-to-treat (ITT) participants who were transfusion independent

Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline

Baseline ( N = 44)

Overall Post-Baseline Average ( N= 44)

OverallChange from Baseline ( N = 44)

The intent-to-treat (ITT) population was defined as all enrolled participants.

Number of Platelet Transfusions by Cycle

Baseline

Overall Post Baseline

Overall Change from Baseline

Cycle 1

Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days

≥ 1 TEAE

≥ 1 NCI Grade 3 or 4 TEAE

≥ TEAE related to study drug

≥ 1 NCI Grade 3 or 4 TEAE related to study drug

≥ 1 serious TEAE

≥ 1 NCI CTC Grade 3 or 4 serious TEAE

≥ 1 serious TEAE related to study drug

TEAE leading to discontinuation of study drug

TEAE leading to study drug dose reduction

TEAE leading to study drug dose interruption

TEAE leading to dose reduction or interruption

TEAE leading to death

Safety Population included enrolled participants who received at least one dose of investigational product and had at least one postdose assessment

Number of Participants With Adverse Events (AE)

The PK population includes all participants with evaluable azacitidine plasma PK profile.

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Azacitidine

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Azacitidine

Maximum Observed Plasma Concentration (Cmax) of Azacitidine

Time to Maximum Plasma Concentration (Tmax) of Azacitidine

Terminal Phase of Half-life (T1/2) of Azacitidine

Apparent Total Plasma Clearance (CL/F) of Azacitidine

Apparent Volume of Distribution (Vd/F) of Azacitidine

Overall Study

Digestive System Diseases

Colorectal Neoplasms

Intestinal Diseases

Rectal Neoplasms

Gastrointestinal Diseases

Gastrointestinal Neoplasms

Intestinal Neoplasms

Digestive System Neoplasms

Rectal Diseases

Micronutrients

Hematinics

Vitamins

Pemetrexed

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Modufolin ( \[6R\] 5,10-methylenetetrahydrofolate) and Pemetrexed

10, 50, 100, 200, and 500 mg/m2 IV on day 1, day 8 day and day 15 of each 21-day cycle. 3 cycles.

[6R] 5,10-methylenetetrahydrofolate (arfolitixorin)

500 mg/m2 IV on day 1 of each 21-day cycle. 3 cycles.

Bengt G Gustavsson, PhD, MD

The purpose of this study is to determine whether an optimal dose of \[6R\] 5,10-methylenetetrahydrofolate (arfolitixorin) in combination with pemetrexed are effective in pre-operative treatment of patients with resectable rectal cancer.

An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate (Arfolitixorin) and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer

An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer

Feasibility is defined as the ability to receive the total planned dose of pemetrexed (i.e., 1500 mg/m) administered over a period of no more than 9 weeks. Feasibility is measured as absence of the following toxicities:

1. CTC grade 4 lasting \>= 7 days, or febrile neutropenia
2. CTC grade 4 thrombocytopenia or grade 3 with bleeding.
3. CTC grade 3 nonhematologic toxicity (excluding nausea and vomiting, isolated CTC grade 3 ALT or AST that returns to the patient's pretreatment CTC grade within 3 weeks, or grade 3 fatigue lasting \<7 days).

Bleeding, anastomosis, leakage, serious infection.

Blood samples are taken before start of study treatment, in conjunction with start of every study drug cycle, and after completed study treatment. HCy measurements performed using HPLC. 5-10-methylenetetrahydrofolate is measured in tissue biopsies (tumor and adjacent mucosa) sampled in conjunction with surgery. The tissue is collected before start of study treatment, during and after completed study treatment. 5,10-methylenetetrahydrofolate levels are measured using LC/MS/MS.

RT-PCR will be used to measure and determine the gene expression levels of the genes FPGS (Folylpolyglutamate synthase) and GGH (Gamma-glutamyl hydrolase). This translational research will be compared with the clinical outcome and toxicity profiles of patients.

Plasma samples will be collected prior to study treatment, and at 10 minutes, 1, 2 and 4 hours after study treatment

Isofol Medical AB

Skin and Connective Tissue Diseases

Breast Neoplasms

Neoplasm Metastasis

Skin Diseases

Breast Diseases

Neoplastic Processes

Capecitabine

Docetaxel

Tubulin Modulators

Antimitotic Agents

Capecitabine 1000 mg/m2 twice daily on days 1-14 of each 3-week cycle.

Capecitabine 500 mg three times daily on days 1-21 of each 3-week cycle

Eligible patients will receive treatment with Capecibatine (1000 mg/ m2 twice daily D1-14 Q3W) plus docetaxel(75 mg/m2, D1,Q3W) for a maximum of 6 cycles, or be treated until disease progression, unacceptable toxicity or patient request for withdrawal, whichever occurs first. Each cycle is 3 weeks in duration.

For the the patients with SD, PR or CR after initiate treatment phrase will enter into maintenance treatment phase.

Docetaxel plus Capecitabine

Capecitabine 1000 mg/m2 twice daily on days 1-14 of each 3-week cycle

Intermittent Capecitabine

Metronomic Capecitabine

Binghe Xu, MD, PhD

Fei Ma, MD

It is a phase III trial to explore the efficacy and safety of metronomic chemotherapy with Capecitabine versus intermittent Capecitabine as maintenance therapy following first-line Capecitabine plus Docetaxel chemotherapy in treatment of HER2-negative metastatic breast cancer(mBC).

Capecitabine Maintenance Therapy Following Capecitabine Combined With Docetaxel in Treatment of mBC

A Randomized Phase III Study of Metronomic vs. Intermittent Capecitabine Maintenance Therapy Following First-line Capecitabine and Docetaxel Therapy in HER2-negative Metastatic Breast Cancer

Time from randomization to progression or death (whichever occurred first).

Adverse events (AEs) and laboratory tests graded according to the NCI CTCAE (version 4.0), premature withdrawals and vital signs. Hand-foot syndrome and diarrhea will be specially interested.

Adverse events of special interest: hand-foot syndrome and diarrhea. The estimated HFS rate will be about 60% from intermittent Capecitabine vs about 10% from metronomic Capecitabine, diarrhea rate will be about 50% from intermittent Capecitabine vs about 10% from metronomic Capecitabine.

Defined as CR+PR, assessed based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria. It will be evaluated in the initial treatment phase and the maintenance treatment phase.

Defined as CR+PR+SD, assessed based on on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria. It will be evaluated in the initial treatment phase and the maintenance treatment phase

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)	NCT01201811	Myelodysplastic...	Azacitidine	18 Years -	Celgene
An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate (Arfolitixorin) and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer	NCT01397305	Rectal Cancer	[6R] 5,10-methy... Pemetrexed	18 Years -	Isofol Medical AB
Capecitabine Maintenance Therapy Following Capecitabine Combined With Docetaxel in Treatment of mBC	NCT01917279	Breast Neoplasm... Neoplasms by Si... Neoplasm Metast... Breast Diseases Skin Diseases	Docetaxel plus ... Intermittent Ca... Metronomic Cape...	18 Years -	ChineseAMS
Hepatic Artery Infusion Chemotherapy Plus Donafenib in Patients With Hepatocellular Carcinoma After Surgery	NCT04962958	Carcinoma Carcinoma, Hepa... Liver Neoplasms Digestive Syste... Antineoplastic ... Donafenib Fluorouracil Oxaliplatin Antimetabolites	Hepatic arteria... Folfox Protocol Donafenib	18 Years - 75 Years	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Phase I/II Study of KRN330 Plus Irinotecan in Patients With Metastatic Colorectal Cancer	NCT00838578	Colorectal Canc...	KRN330 Irinotecan	18 Years -	Kyowa Kirin Co., Ltd.

Spots Global Cancer Trial Database for antimetabolites