Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Tivozanib

Antimetabolites

Protein Kinase Inhibitors

Enzyme Inhibitors

Tivozanib 1.0 mg or 1.5 mg oral once daily for 2 weeks followed by 1 week off. Capecitabine 825 mg/m2, 1000 mg/m2, or 1250 mg/m2, oral twice daily for 2 weeks followed by 1 week off. 1 cycle= 3 weeks. Cycles will be repeated in the absence of disease progression or unacceptable toxicity.

tivozanib (AV-951) and capecitabine (Xeloda®)

Shefali Agarwal, M.D.

This is an open-label, multi-center, dose-finding study of tivozanib administered in combination with capecitabine. During the dose-escalation portion, sequential cohorts of subjects with advanced solid tumors will be enrolled in order to establish the maximum tolerated dose (MTD). If the MTD is not reached, the recommended Phase 2 dose (RP2D) will be determined. In the expansion cohort, subjects with locally advanced or metastatic breast or colon cancer will be enrolled at MTD (or RP2D) to further evaluate safety and activity of this combination in these tumor types.

This is a Phase Ib, open-label, multi-center, dose-escalation study of orally administered tivozanib in combination with capecitabine to approximately 24 subjects with advanced solid tumors and, in the expanded MTD cohort, subjects with locally advanced or metastatic breast or colorectal cancer. This study is designed to evaluate the safety, tolerability, dose-limiting toxicities, maximum tolerated dose, pharmacokinetic, and antineoplastic activity. The number of cohorts evaluated and the maximum doses to be administered will depend upon the observed tolerability. Dose level "0", tivozanib HCl 1.5 mg and capecitabine 1000 mg/m² BID, is the starting dose level. Once assigned to a cohort, each subject will continue to be treated at the same dose level and schedule throughout the course of the study.

A Trial of Tivozanib (AV-951) in Combination With Capecitabine (Xeloda®) in Subjects With Advanced Solid Tumors

A Phase 1b, Open-Label, Dose-Escalating Trial of Tivozanib (AV-951) in Combination With Capecitabine (Xeloda®) in Subjects With Advanced Solid Tumors

Assessment of any dose-limiting toxcities

PK parameters of tivozanib and capecitabine will be calculated from serum and plasma levels. These will be summarized descriptively and presented by visit and dose cohort. PK parameters will be calculated using non compartmental and/or compartmental models and PK parameters will be summarized and presented. The mean (± STDEM) concentration-time profiles of tivozanib, capecitabine, and their metabolite(s) will be presented for each dose.

Disease and response assessments will be determined using Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0). Disease assessment is to include disease classification, tumor marker assessments, and diagnostic imaging / measurement of marker lesions. Computerized tomography (CT) will be considered the standard method for evaluating disease status. All subjects should have a CT scan (or MRI) of the head, chest, abdomen, and pelvis at baseline. The location and dimensions of "marker" lesions will be documented.

AVEO Pharmaceuticals, Inc.

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Hematinics

Liver Extracts

Primary objectives :

To evaluate the tumor response rate, local control rate and compliance (acute and late toxicity, esp. gastrointestinal tract toxicity) of concurrent chemo-radiotherapy with oral capecitabine in patients with unresectable locally advanced pancreatic carcinoma

Secondary objectives :

To evaluate the impact of concurrent chemo-radiotherapy with oral capecitabine in patients with unresectable locally advanced pancreatic carcinoma by analyzing the progression-free survival rate and overall survival rate.

Capecitabine is administered orally at a dose of 800 mg/m2 twice daily (total daily dose 1600mg/ m2) continuous regimen regimen during RT (5 days of treatment followed by a 2 day rest: Saturday and Sunday). Capecitabine is given approximately 12 hours apart and taken orally with water within 30 minutes after ingestion of food (breakfast or dinner).

Capecitabine (Xeloda®)

Radiation dose and planning

1. Total dose 55.8Gy, 28 fractions, 6-7 weeks (1.8 Gy/day). A cone down after 45 Gy will be performed to emcompass GTV with a margin of 1-1.5cm.
2. Dose prescription : 90% isodose volume of prescribed dose encompassed PTV
3. The dose-volume histogram (DVH) of targets, such as GTV, CTV, and PTV, and the normal tissues, such as the liver, duodenum, stomach, the kidneys, spinal cord, etc., was calculated.

Localization, simulation and immobilization

Tae Hyun Kim

The only curative option for pancreatic cancer patients is surgery, but the patients within 20% of them are possible for a radical surgery. Accordingly, concurrent chemo-radiation therapy is generally used for palliation of unresectable pancreatic cancer patients. So far, the use of 5-fluorouracil (5-FU) was the traditional method of chemotherapy. However, these days, oral anti-cancer medicine, capecitabine(Xeloda®), was developed and considered as an alternative medicine of 5-fluorouracil (5-FU). Furthermore, according to the recent results of clinical trials, the clinical use of capecitabine(Xeloda®) with radiation therapy was proved to be very effective and safe. The purpose of this trial is to improve the therapeutic effects by using proton therapy and chemotherapy concurrently.

Concurrent Chemo-radiotherapy With Capecitabine for Unresectable Locally Advanced Pancreatic Carcinoma

A Phase II Study of Concurrent Chemo-radiotherapy With Capecitabine for Unresectable Locally Advanced Pancreatic Carcinoma

National Cancer Center, Korea

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Disease Progression

Breast Diseases

Skin Diseases

Docetaxel

Tubulin Modulators

Antimitotic Agents

1250 mg/m\^2 capecitabine (Xeloda®) orally twice a day on days 1 to 14 of each 3 week cycle, in combination with docetaxel (Taxotere®) 75 mg/m\^2 intravenous on day 1 of each 3 week cycle.

825 mg/m\^2 capecitabine orally twice a day on days 1 to 14 of each 3 week cycle, in combination with docetaxel 75 mg/m\^2 intravenous on day 1 of each 3 week cycle.

825 mg/m\^2 or 1250 mg/m2 orally twice a day on days 1 to 14 of each 3 week cycle.

capecitabine (Xeloda®)

75 mg/m\^2 intravenous on day 1 of each 3 week cycle

docetaxel (Taxotere®)

Clinical Trials

This 2 arm study compared the efficacy and safety of label dose of capecitabine (Xeloda®) to that of a lower dose of Xeloda® plus docetaxel (Taxotere®) in patients with locally advanced or metastatic breast cancer after failure of chemotherapy with an anthracycline. Patients were randomized to receive either 1250 mg/m\^2 or 825 mg/m\^2 orally twice a day (po bid) on days 1-14 of each 3 week cycle, in combination with Taxotere® 75 mg/m2 intravenous (iv) on day 1 of each 3 week cycle. The anticipated time on study treatment was until disease progression and the target sample size was 440 individuals.

A Study to Assess Capecitabine (Xeloda®) in Patients With Locally Advanced or Metastatic Breast Cancer

A Randomized, Open-label Study of the Effect of Different Dosing Regimens of Xeloda® in Combination With Taxotere® on Disease Progression in Patients With Locally Advanced and/or Metastatic Breast Cancer

Progression Free Survival was defined as the time from the date of randomization to the day of documented disease progression or death due to any cause.

According to Response Evaluation Criteria in Solid Tumors (RECIST) criteria: CR is defined as the disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the nadir sum LD.

For patients with Best Overall Response being Complete Response (CR) or Partial Response (PR), time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR were met. The percentage of participants with overall response within the given time ranges in each of the categories: Weeks 1-6, 7-12, 13-18, 19-24, 25-30, 31-36, and 43-48 are reported.

Duration of overall response was measured from the time that measurement criteria were first met for Complete Response or Partial Response until the first date that progressive disease or death was documented.

The time to treatment failure was the time from the date of randomization to the first occurrence of any of the following events:

* adverse events
* insufficient therapeutic response (disease progression)
* death
* failure to return
* refusing treatment/being unwilling to cooperate
* withdrawing consent.

Overall Survival was measured as the time from the date of randomization to the date of death.

An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.

A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is Life-Threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Additional information about Adverse Events can be found in the Adverse Event Section.

Hoffmann-La Roche

Safety Population included all randomized participants who received study drug. Note: 14 patients randomized to the 1250 mg/m\^2 arm actual received an initial dose that ranged from 480 to 984 mg/m\^2 so were included in the 825 mg/m\^2 arm for safety.

1250 mg/m^2 Capecitabine + Docetaxel

825 mg/m^2 Capecitabine + Docetaxel

Total

Age Continuous

Sex: Female, Male

Medical Communications

Per protocol population included all participants who received at least one dose of study and who did not have any major protocol deviations.

Time to Progression of Disease or Death

Intent to treat population included all randomized participants.

Percentage of Participants With Best Overall Response Being Complete Response (CR) or Partial Response (PR)

Week 1-6

Week 7-12

Week 13-18

Week 19-24

Week 25-30

Week 31-36

Week 43-48

Time to Overall Response

Duration of Overall Response

Safety Population included all randomized participants who received study drug. Note: 14 patients randomized to 1250 mg/m\^2 actual received an initial dose that ranged from 480 to 984 mg/m\^2 so are included in the 825 mg/m\^2 arm for safety.

Time to Treatment Failure

Overall Survival

Adverse Events

Serious Adverse Events

Number of Participants With Adverse Events and Serious Adverse Events

Overall Study

Rectal Neoplasms

Micronutrients

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

Arm 1 will receive chemotherapy before chemoradiation. This is called induction neoadjuvant chemotherapy arm (INCT). The neoadjuvant chemotherapy regimen is prescribed specifically as 8 cycles of FOLFOX or 5 cycles of CapeOX over a period of approximately 15-16 weeks. Endoscopic exam (2-4 wks) after chemotherapy. If stable or response then pt will have radiation with either 5-FU or capecitabine.

Arm 2 will receive chemoradiation before chemotherapy This is called the consolidation neoadjuvant chemotherapy arm (CNCT). Pt will have 6 weeks of chemoradiation therapy. Along with the radiation the pt will receive either 5-FU or capecitabine. 2-4 weeks after pt will have endoscopic exam and if stable or response pt will have will have 8 cycles of FOLFOX or 6 cycles of CapeOX.

Oxaliplatin (OXAL)

5-Fluorouracil (5-FU)

intensity modulated radiotherapy (IMRT)

Quality of Life Questionnaires

DRE-Endoscopy

Julio Garcia Aguilar, MD, PhD

The study is designed to test the hypothesis that patients with Locally advanced rectal cancer ( LARC) treated with Total neoadjuvant therapy (TNT) and Total mesorectal excision (TME) or Non-operative management (NOM) will have an improved 3-year disease-free survival (DFS) compared to patients with similar tumors treated with Chemoradiation therapy (CRT), Total mesorectal excision (TME) and Adjuvant chemotherapy (ACT).

Trial Evaluating 3-year Disease Free Survival in Patients With Locally Advanced Rectal Cancer Treated With Chemoradiation Plus Induction or Consolidation Chemotherapy and Total Mesorectal Excision or Non-operative Management

A Phase II Multicenter Randomized Trial Evaluating 3-year Disease Free Survival in Patients With Locally Advanced Rectal Cancer Treated With Chemoradiation Plus Induction or Consolidation Chemotherapy and Total Mesorectal Excision or Non-operative Management

3-year DFS will be defined as the percentage of patients alive without recurrence of disease at 3 years measured from the date of randomization

Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Trial of Tivozanib (AV-951) in Combination With Capecitabine (Xeloda®) in Subjects With Advanced Solid Tumors	NCT01306630	Advanced Solid ... Locally Advance...	tivozanib (AV-9...	18 Years -	AVEO Pharmaceuticals, Inc.
Concurrent Chemo-radiotherapy With Capecitabine for Unresectable Locally Advanced Pancreatic Carcinoma	NCT00658840	Pancreatic Canc...	Capecitabine (X... Localization, s...	18 Years -	National Cancer Center, Korea
Concurrent Chemo-radiotherapy With Capecitabine for Unresectable Locally Advanced Pancreatic Carcinoma	NCT00658840	Pancreatic Canc...	Capecitabine (X... Localization, s...	18 Years -	National Cancer Center, Korea
A Study to Assess Capecitabine (Xeloda®) in Patients With Locally Advanced or Metastatic Breast Cancer	NCT00077857	Breast Cancer	capecitabine (X... docetaxel (Taxo...	18 Years -	Hoffmann-La Roche
Trial Evaluating 3-year Disease Free Survival in Patients With Locally Advanced Rectal Cancer Treated With Chemoradiation Plus Induction or Consolidation Chemotherapy and Total Mesorectal Excision or Non-operative Management	NCT02008656	Rectal Cancer	Oxaliplatin (OX... 5-Fluorouracil ... Leucovorin Capecitabine (X... intensity modul... Quality of Life... DRE-Endoscopy	18 Years -	Memorial Sloan Kettering Cancer Center
Concurrent Chemo-radiotherapy With Capecitabine for Unresectable Locally Advanced Pancreatic Carcinoma	NCT00658840	Pancreatic Canc...	Capecitabine (X... Localization, s...	18 Years -	National Cancer Center, Korea

Spots Global Cancer Trial Database for capecitabine (xeloda®)