A Dose-Escalation to Rash Study of Tarceva (Erlotinib) Plus Gemcitabine in Patients With Metastatic Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00652366
First received: April 1, 2008
Last updated: January 27, 2015
Last verified: January 2015
  Purpose

This study will compare the efficacy and safety of escalating versus standard doses to rash of Tarceva, in combination with gemcitabine, in patients with metastatic pancreatic cancer. During a 4 week run-in period, all patients will receive Tarceva 100mg/day po plus gemcitabine 1000mg/m2 iv on days 1, 8,15 and 22. After 4 weeks, patients who have not developed rash, or only develop grade 1 rash, will be randomized to one of 2 groups. Group 1 will receive a starting dose of Tarceva 150mg po daily, increased in steps of 50mg every 2 weeks up to a maximum of 250mg/day po, until development of grade 2 rash or other dose-limiting toxicity. Group 2 will continue to receive Tarceva 100mg/day po. All patients will continue to receive gemcitabine 1000mg/m2 iv on days 1, 8 and 15 of each 4 week cycle. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.


Condition Intervention Phase
Pancreatic Cancer
Drug: Erlotinib, escalating dose
Drug: Erlotinib, standard dose
Drug: Gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Dose-escalation to Rash Study to Assess the Effect of Tarceva in Combination With Gemcitabine on Overall Survival in Patients With Metastatic Pancreatic Cancer.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants Who Died Assessed From Point of Randomization [ Time Frame: Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months. ] [ Designated as safety issue: No ]
    Overall survival (OS) assessed from the point of randomization was defined as the time from randomization to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive.

  • OS Assessed From Point of Randomization [ Time Frame: Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months. ] [ Designated as safety issue: No ]
    OS assessed from the point of randomization was defined as the median time, in months, from randomization to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive. The 95 percent (%) confidence interval (CI) was determined using Kaplan-Meier methodology.


Secondary Outcome Measures:
  • Percentage of Participants With Disease Progression or Death as Assessed From Point of Randomization [ Time Frame: Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months. ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) as assessed from the point of randomization was defined as the time from randomization to the first occurrence of progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause. For target lesions (TLs), PD was defined as at least a 20% increase in the sum of longest diameter (SLD) of TLs, taking as reference the smallest SLD recorded since the treatment started. For non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment.

  • PFS Assessed From Point of Randomization [ Time Frame: Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months. ] [ Designated as safety issue: No ]
    PFS assessed from the point of randomization was defined as the median time, in weeks, from randomization to disease progression or death due to any cause. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment. The 95% CI was determined using Kaplan-Meier methodology.

  • Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST [ Time Frame: BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months. ] [ Designated as safety issue: No ]
    BOR was defined as a confirmed CR or PR for at least 4 weeks. CR was defined as the disappearance of all TLs. PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline (BL) SLD. The 95% CI for one sample binomial was determined using Pearson-Clopper method.

  • Percentage of Participants With a CR, PR, Stable Disease (SD), or PD According to RECIST [ Time Frame: BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months. ] [ Designated as safety issue: No ]
    CR was defined as the disappearance of all TLs. PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.

  • Percentage of Participants With SD (Maintained for at Least 8 Weeks) or CR or PR (Maintained for at Least 4 Weeks) According to RECIST [ Time Frame: BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months. ] [ Designated as safety issue: No ]
    Disease control was defined as a participant with a response of CR or PR for at least 4 weeks at any time during treatment, or SD that was maintained for at least 8 weeks after the start of treatment. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.

  • Percentage of Participants Who Died as Assessed From Start of 4-Week Run-In [ Time Frame: BL and weekly thereafter for up to 46 months. ] [ Designated as safety issue: No ]
    OS assessed from the start of the 4-week run in period was defined as the time from BL to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive.

  • OS Assessed From Start of 4-Week Run-In [ Time Frame: BL and weekly thereafter for up to 46 months. ] [ Designated as safety issue: No ]
    OS assessed from the start of the 4-week run in period was defined as the median time, in months, from BL to the date of death, due to any cause. Participants who were still alive at the time of analysis were censored at the date they were last known to be alive. The 95% CI was determined using Kaplan-Meier methodology.

  • Percentage of Participants With Disease Progression or Death as Assessed From the Start of 4-Week Run-In [ Time Frame: BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months. ] [ Designated as safety issue: No ]
    PFS as assessed from the start of 4-week run-in was defined as the time from BL to the first occurrence of PD according to RECIST or death due to any cause. For TLs, PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, PD was defined as unequivocal progression of existing NTLs. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment.

  • PFS Assessed From the Start of 4-Week Run-In [ Time Frame: BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months. ] [ Designated as safety issue: No ]
    PFS assessed from the start of 4-week run-in was defined as the median time, in weeks, from BL to disease progression or death due to any cause. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment. The 95% CI was determined using Kaplan-Meier methodology.


Enrollment: 467
Study Start Date: May 2008
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Gemcitabine, Erlotinib Standard Dose
Participants received erlotinib, 100 milligrams (mg), orally (PO), once daily until disease progression or unacceptable toxicity. Participants also received gemcitabine, 1000 mg per (/) square meter (m^2), intravenously (IV), on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression or unacceptable toxicity.
Drug: Erlotinib, standard dose
100mg, PO, once daily
Other Name: Tarceva
Drug: Gemcitabine
1000 mg/m2, IV, on days 1,8 and 15 of each 4 week cycle
Experimental: Gemcitabine, Erlotinib Escalating Dose
Participants received erlotinib, beginning at 150 mg/day, PO, once daily, and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal. Participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression or unacceptable toxicity.
Drug: Erlotinib, escalating dose
100mg, PO, once daily, escalating to a maximum of 250mg, PO, once daily
Other Name: Tarceva
Drug: Gemcitabine
1000 mg/m2, IV, on days 1,8 and 15 of each 4 week cycle

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • histologically or cytologically confirmed pancreatic cancer with measurable or non-measurable metastatic disease;
  • ECOG performance status of 0-1.

Exclusion Criteria:

  • local, or locally advanced, pancreatic cancer;
  • prior systemic treatment for metastatic pancreatic cancer;
  • <=6 months since last adjuvant chemotherapy;
  • other malignancies within last 5 years, except for adequately treated cancer in situ of the cervix, or basal or squamous cell skin cancer.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00652366

  Show 89 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00652366     History of Changes
Other Study ID Numbers: BO21128, 2007-003751-37
Study First Received: April 1, 2008
Results First Received: December 8, 2014
Last Updated: January 27, 2015
Health Authority: Italy:National Institue of Health

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Erlotinib
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2015