Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Pancreatic Neoplasms

Disease Progression

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Capecitabine

Bevacizumab

Erlotinib Hydrochloride

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

bevacizumab [Avastin]

Escalating doses of 500/650/750/900mg/m2 bid

capecitabine [Xeloda]

erlotinib [Tarceva]

Clinical Trials

This 2 part study will evaluate the safety and efficacy of a combination of Avastin, Tarceva and Xeloda (ATX) as second-line treatment in patients with locally advanced and/or metastatic pancreatic cancer. In the first part of the study, cohorts of patients will receive escalating doses of combination treatment to determine the maximum tolerated dose. The recommended dose will be used in the second part of the study to determine the efficacy of the ATX regime, in terms of its effect on disease progression. The anticipated time on study treatment is 3-12 months, and the target sample size is \<100 individuals.

ATX Study:A Study of Avastin (Bevacizumab), Tarceva (Erlotinib) and Xeloda (Capecitabine) in Patients With Locally Advanced and/or Metastatic Pancreatic Cancer

An Open Label Study to Evaluate the Safety and Effect on Disease Progression of Triple Combination Treatment With Erlotinib (Tarceva), Bevacizumab (Avastin), and Capecitabine (Xeloda) in Patients With Locally Advanced and/or Metastatic Pancreatic Cancer (REBECA-Trial).

MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33 percent (%) of participants of the same quality category. DLT was defined as any greater than or equal to (\>=) Grade (G) 3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to adverse events (AEs).

MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as \>= G3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs.

Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33% of participants of the same quality category. DLT was defined as \>= G3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.

Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as \>= G3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.

As per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions (target and non-target lesions) or the unequivocal progression of existing non-target lesions.

A participant was defined as having controlled disease if they sustained a Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) during the assessment. As per RECIST v1.1, CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level; PR is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter; SD for target lesions is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started and SD for non-target lesions defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.

Clinical benefit response was defined as a composite of pain control, Karnofsky performance status (KPS), and weight. The KPS allows participants to be classified as per their functional impairment (abnormal function). It was recorded on an 11-point scale; 0= "dead" to 100= "Normal, no complaints, no evidence of disease" and sub-divided to 3 categories; 0 to 40 = "Unable to care for self, requires institutional or hospital care or equivalent, disease may be rapidly progressing"; 50 to 70= "Unable to work, able to live at home and care for most personal needs, varying amount of assistance needed and 80 to 100= "Able to carry on normal activity; no special care is needed".

Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive.

Hoffmann-La Roche

Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

ERL+BEV+CAP Dose Level-1

Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

ERL+BEV+CAP Dose Level-2

Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

ERL+BEV+CAP Dose Level-3

Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

ERL+BEV+CAP Dose Level-4

Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

ERL+BEV+CAP Dose Level-5

Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

ERL+BEV+CAP Dose Level-6

Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (Dose levels \[DL\]-1, 2, 3, 4, 5 and 6) were administered either oral 100 mg or 150 mg of erlotinib tablet daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

Triple Combination (Bevacizumab/Erlotinib/Capecitabine)

Age, Continuous

Sex: Female, Male

Per-protocol population: All participants who received at least 1 evaluation period of 3 cycles of the complete study regimen (of all 3 drugs) at the recommended dose unless withdrawn from therapy earlier because of toxicity.

Planned Part 2 of the study was not implemented and outcome measures related to Part 2 were not analyzed.

Medical Communications

Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

Part 1: Maximum Tolerated Dose (MTD) of Capecitabine

Dose-escalation was performed using a substance related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DL-1, 2, 3, 4, 5 and 6) were administered with either 100 mg or 150 mg of erlotinib daily orally, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

Part 1: MTD of Erlotinib

Erlotinib (n=6,6,6,6,3,3)

OSI-420 (n=6,6,6,6,3,3)

Capecitabine (n=6,6,6,6,3,3)

5'-DFCR (n=5,5,6,6,3,3)

5'-DFUR (n=4,5,6,6,3,3)

Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m\^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively.

Part 1: Maximum Serum Concentration (Cmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR] and 5'-Deoxy-5-Fluorouridine [5'-DFUR])

Part 1: MTD of Bevacizumab

Part 1: Preliminary Recommended Dose (PRD) of Capecitabine for Part 2

Part 1: Time to Reach Cmax (Tmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)

Part 1: Last Quantifiable Drug Concentration (Clast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)

Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)

Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented.

Part 2: Percentage of Participants Free From Disease Progression

Part 2: Percentage of Participants With Disease Control

Part 2: Percentage of Participants With Clinical Benefit Response

Part 2: Overall Survival

Part 1: PRD of Erlotinib for Part 2

Part 1: PRD of Bevacizumab for Part 2

Participants were administered oral 100 milligrams (mg) of erlotinib (ERL) tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 milligrams per kilogram (mg/kg) of bevacizumab (BEV) intravenous (IV) infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 milligrams per square meter (mg/m\^2) of capecitabine (CAP) tablet twice daily (BID) within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.

Spots Global Cancer Trial Database for ATX Study:A Study of Avastin (Bevacizumab), Tarceva (Erlotinib) and Xeloda (Capecitabine) in Patients With Locally Advanced and/or Metastatic Pancreatic Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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