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

NCT00925769 | Completed Phase 1 Results

• 2 other identifiers: ML207842008-004444-36
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (6)

• Part 1: Maximum Tolerated Dose (MTD) of Capecitabine

  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).

  Up to Week 6 (Cycle 1-3)

• Part 1: MTD of Erlotinib

  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.

  Up to Week 6 (Cycle 1-3)

• Part 1: MTD of Bevacizumab

  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.

  Up to Week 6 (Cycle 1-3)

• Part 1: Preliminary Recommended Dose (PRD) of Capecitabine 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 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.

  Up to Week 6 (Cycle 1-3)

• Part 1: PRD of Erlotinib 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.

  Up to Week 6 (Cycle 1-3)

• Part 1: PRD of Bevacizumab 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.

  Up to Week 6 (Cycle 1-3)

Secondary Outcomes (8)

• 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])

  CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)

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

  CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)

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

  CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)

• 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)

  CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)

• Part 2: Percentage of Participants Free From Disease Progression

  Month 6

Study Arms (1)

1

EXPERIMENTAL

Drug: bevacizumab [Avastin]; Drug: capecitabine [Xeloda]; Drug: erlotinib [Tarceva]

Interventions

bevacizumab [Avastin] DRUG

Escalating doses of 5/10mg/kg q2w

1

capecitabine [Xeloda] DRUG

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

1

erlotinib [Tarceva] DRUG

Escalating doses of 100/150mg daily

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adult patients, \>=18 years of age;
• pancreatic cancer with locally advanced and/or metastatic disease (stage IV);
• chemonaive for metastatic or locally advanced disease;
• ECOG performance status of 0-2.

You may not qualify if:

• local (stage IA to IIB)and locally advanced (stage III) pancreatic cancer;
• previous exposure to Avastin, Tarceva or Xeloda;
• other primary tumor within the last 5 years prior to enrollment, except for adequately treated cancer in situ of cervix, or basal cell skin cancer;
• current or recent chronic use of aspirin (\>325 mg/day) or full therapeutic dose of anticoagulants or thrombolytic agents.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (2)

Unknown Facility

Vienna, 1100, Austria

Location

Unknown Facility

Vienna, 1130, Austria

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Bevacizumab; Capecitabine; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2009
• First Posted: June 22, 2009
• Study Start: January 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: August 7, 2015
• Results First Posted: August 7, 2015

Record last verified: 2015-07

Locations

AU (2)