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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00652366




Registration number
NCT00652366
Ethics application status
Date submitted
1/04/2008
Date registered
3/04/2008
Date last updated
11/02/2015

Titles & IDs
Public title
A Dose-Escalation to Rash Study of Tarceva (Erlotinib) Plus Gemcitabine in Patients With Metastatic Pancreatic Cancer
Scientific 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.
Secondary ID [1] 0 0
2007-003751-37
Secondary ID [2] 0 0
BO21128
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Erlotinib, escalating dose
Treatment: Drugs - Erlotinib, standard dose
Treatment: Drugs - Gemcitabine

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.

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.


Treatment: Drugs: Erlotinib, escalating dose
100mg, PO, once daily, escalating to a maximum of 250mg, PO, once daily

Treatment: Drugs: Erlotinib, standard dose
100mg, PO, once daily

Treatment: Drugs: Gemcitabine
1000 mg/m2, IV, on days 1,8 and 15 of each 4 week cycle

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Died Assessed From Point of Randomization - 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.
Timepoint [1] 0 0
Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.
Primary outcome [2] 0 0
OS Assessed From Point of Randomization - 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.
Timepoint [2] 0 0
Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.
Secondary outcome [1] 0 0
Percentage of Participants With Disease Progression or Death as Assessed From Point of Randomization - 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.
Timepoint [1] 0 0
Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.
Secondary outcome [2] 0 0
PFS Assessed From Point of Randomization - 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.
Timepoint [2] 0 0
Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.
Secondary outcome [3] 0 0
Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST - 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.
Timepoint [3] 0 0
BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.
Secondary outcome [4] 0 0
Percentage of Participants With a CR, PR, Stable Disease (SD), or PD According to RECIST - 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.
Timepoint [4] 0 0
BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.
Secondary outcome [5] 0 0
Percentage of Participants With SD (Maintained for at Least 8 Weeks) or CR or PR (Maintained for at Least 4 Weeks) According to RECIST - 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.
Timepoint [5] 0 0
BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.
Secondary outcome [6] 0 0
Percentage of Participants Who Died as Assessed From Start of 4-Week Run-In - 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.
Timepoint [6] 0 0
BL and weekly thereafter for up to 46 months.
Secondary outcome [7] 0 0
OS Assessed From Start of 4-Week Run-In - 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.
Timepoint [7] 0 0
BL and weekly thereafter for up to 46 months.
Secondary outcome [8] 0 0
Percentage of Participants With Disease Progression or Death as Assessed From the Start of 4-Week Run-In - 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.
Timepoint [8] 0 0
BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months.
Secondary outcome [9] 0 0
PFS Assessed From the Start of 4-Week Run-In - 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.
Timepoint [9] 0 0
BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
- Canberra
Recruitment hospital [2] 0 0
- Liverpool
Recruitment hospital [3] 0 0
- St. Leonards
Recruitment hospital [4] 0 0
- Sydney
Recruitment hospital [5] 0 0
- Brisbane
Recruitment hospital [6] 0 0
- Adelaide
Recruitment hospital [7] 0 0
- Ballarat
Recruitment hospital [8] 0 0
- Frankston
Recruitment postcode(s) [1] 0 0
2606 - Canberra
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2065 - St. Leonards
Recruitment postcode(s) [4] 0 0
2076 - Sydney
Recruitment postcode(s) [5] 0 0
4101 - Brisbane
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
03350 - Ballarat
Recruitment postcode(s) [8] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Florencio Varela
Country [3] 0 0
Argentina
State/province [3] 0 0
Rosario
Country [4] 0 0
Argentina
State/province [4] 0 0
Santa Fe
Country [5] 0 0
Austria
State/province [5] 0 0
Salzburg
Country [6] 0 0
Austria
State/province [6] 0 0
Wien
Country [7] 0 0
Belgium
State/province [7] 0 0
Antwerpen
Country [8] 0 0
Belgium
State/province [8] 0 0
Bruxelles
Country [9] 0 0
Belgium
State/province [9] 0 0
Gent
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Belgium
State/province [11] 0 0
Liege
Country [12] 0 0
Brazil
State/province [12] 0 0
BA
Country [13] 0 0
Brazil
State/province [13] 0 0
MG
Country [14] 0 0
Brazil
State/province [14] 0 0
RS
Country [15] 0 0
Brazil
State/province [15] 0 0
SP
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Croatia
State/province [17] 0 0
Zagreb
Country [18] 0 0
Denmark
State/province [18] 0 0
Herlev
Country [19] 0 0
Denmark
State/province [19] 0 0
Hillerod
Country [20] 0 0
Denmark
State/province [20] 0 0
København
Country [21] 0 0
France
State/province [21] 0 0
Angers
Country [22] 0 0
France
State/province [22] 0 0
Besancon
Country [23] 0 0
France
State/province [23] 0 0
Brest
Country [24] 0 0
France
State/province [24] 0 0
Paris
Country [25] 0 0
France
State/province [25] 0 0
St-Priest-En-Jarez
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Germany
State/province [27] 0 0
Bochum
Country [28] 0 0
Germany
State/province [28] 0 0
Bonn
Country [29] 0 0
Germany
State/province [29] 0 0
Esslingen
Country [30] 0 0
Germany
State/province [30] 0 0
Halle
Country [31] 0 0
Germany
State/province [31] 0 0
Hamburg
Country [32] 0 0
Germany
State/province [32] 0 0
Hamm
Country [33] 0 0
Germany
State/province [33] 0 0
Kaiserslautern
Country [34] 0 0
Germany
State/province [34] 0 0
Leipzig
Country [35] 0 0
Germany
State/province [35] 0 0
Marburg
Country [36] 0 0
Germany
State/province [36] 0 0
Muenchen
Country [37] 0 0
Germany
State/province [37] 0 0
Mönchengladbach
Country [38] 0 0
Germany
State/province [38] 0 0
Saarbruecken
Country [39] 0 0
Germany
State/province [39] 0 0
Trier
Country [40] 0 0
Germany
State/province [40] 0 0
Ulm
Country [41] 0 0
Greece
State/province [41] 0 0
Heraklion
Country [42] 0 0
Greece
State/province [42] 0 0
Thessaloniki
Country [43] 0 0
Hong Kong
State/province [43] 0 0
Hong Kong
Country [44] 0 0
Israel
State/province [44] 0 0
Haifa
Country [45] 0 0
Israel
State/province [45] 0 0
Jerusalem
Country [46] 0 0
Israel
State/province [46] 0 0
Petach Tikva
Country [47] 0 0
Israel
State/province [47] 0 0
Tel Aviv
Country [48] 0 0
Israel
State/province [48] 0 0
Zerifin
Country [49] 0 0
Italy
State/province [49] 0 0
Abruzzo
Country [50] 0 0
Italy
State/province [50] 0 0
Campania
Country [51] 0 0
Italy
State/province [51] 0 0
Friuli-Venezia Giulia
Country [52] 0 0
Italy
State/province [52] 0 0
Piemonte
Country [53] 0 0
Italy
State/province [53] 0 0
Puglia
Country [54] 0 0
Italy
State/province [54] 0 0
Toscana
Country [55] 0 0
Lithuania
State/province [55] 0 0
Vilnius
Country [56] 0 0
Mexico
State/province [56] 0 0
Distrito Federal
Country [57] 0 0
Poland
State/province [57] 0 0
Gliwice
Country [58] 0 0
Poland
State/province [58] 0 0
Lublin
Country [59] 0 0
Poland
State/province [59] 0 0
Poznan
Country [60] 0 0
Poland
State/province [60] 0 0
Warszawa
Country [61] 0 0
Romania
State/province [61] 0 0
Brasov
Country [62] 0 0
Romania
State/province [62] 0 0
Bucuresti
Country [63] 0 0
Romania
State/province [63] 0 0
Cluj Napoca
Country [64] 0 0
Romania
State/province [64] 0 0
Sibiu
Country [65] 0 0
Serbia
State/province [65] 0 0
Belgrade
Country [66] 0 0
Serbia
State/province [66] 0 0
Sremska Kamenica
Country [67] 0 0
Singapore
State/province [67] 0 0
Singapore
Country [68] 0 0
Spain
State/province [68] 0 0
Madrid
Country [69] 0 0
Taiwan
State/province [69] 0 0
Taipei
Country [70] 0 0
United Kingdom
State/province [70] 0 0
London
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Salisbury

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00652366
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications