A Phase I Dose Escalation Trial of Afatinib Plus Gemcitabine or Plus Docetaxel

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01251653
First received: December 1, 2010
Last updated: April 22, 2016
Last verified: April 2016

December 1, 2010
April 22, 2016
November 2010
April 2015   (final data collection date for primary outcome measure)
Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD). [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
DLT was based on following criterions: 1. Grade 4 uncomplicated (not associated with fever >38.5° C (Celsius)) neutropenia for ≥7 days. 2. Grade 3 or 4 neutropenia concomitant with fever >38.5º C or Grade ≥3 infection. 3. Platelet count of <25x 10^9/L or <50x 10^9/L with bleeding requiring whole blood transfusion. 4. Grade ≥3 non-haematological toxicity (except untreated nausea, untreated vomiting, or untreated diarrhoea). 5. Grade ≥2 decrease in cardiac left ventricular function. 6. Grade ≥2 worsening of renal function as measured by serum creatinine, newly developed proteinuria, or a newly developed decrease in glomerular filtration rate. Toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0
The primary objective is to determine the maximum tolerated dose (MTD) of oral Afatinib given in combination with gemcitabine or docetaxel in patients with relapsed or refractory tumors [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01251653 on ClinicalTrials.gov Archive Site
  • The Incidence and Intensity of AEs With Grading According to CTCAE. [ Time Frame: From first drug administration until 28 days after last drug administration, up to 717 days. ] [ Designated as safety issue: Yes ]
    The incidence and intensity of adverse events with grading according to CTCAE. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
  • Best Overall Response According to RECIST v1.1 Criteria [ Time Frame: From first drug administration until 28 days after last drug administration, up to 717 days. ] [ Designated as safety issue: No ]
    Best overall response (according to Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) was the best response recorded at any time from the date of the first administration of afatinib or gemcitabine/docetaxel to the end of treatment (EOT). Partial response is for patients with measurable disease. Missing categories signifies that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed.
  • Disease Control According to RECIST v1.1 [ Time Frame: From first drug administration until 28 days after last drug administration, up to 717 days. ] [ Designated as safety issue: No ]
    Disease control according to RECIST v1.1 Disease control is complete response, partial response or stable disease for measurable patients and complete response or non−CR/non−PD for non−measurable patients. Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed.
  • Objective Response According to RECIST v1.1 [ Time Frame: From first drug administration until 28 days after last drug administration, up to 717 days. ] [ Designated as safety issue: No ]
    Objective response according to RECIST v1.1. Objective response is complete response or partial response for patients with measurable disease. Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed.
  • Time to Objective Response According to RECIST v1.1 [ Time Frame: 6 weeks, 12 weeks and 24 weeks ] [ Designated as safety issue: No ]
    Objective response according to RECIST v1.1. Objective response is complete response or partial response for patients with measurable disease. Time to objective response is the time from the start of treatment to the date of first documented complete response or partial response. Descriptive analyses has been performed for the time to objective response (N(%) of patients with first occurrence of objective response at 6, 12 and 24 weeks). Onset of objective response is derived for patient with measurable disease.
  • Duration of Objective Response According to RECIST v1.1 [ Time Frame: From the first documented complete response or partial response to the time of disease progression or death ] [ Designated as safety issue: No ]
    Duration of objective response was the time from the first documented complete response or partial response to disease progression or death.
  • Duration of Disease Control According to RECIST v1.1 [ Time Frame: From the first administration of study medication to the time of disease progression or death ] [ Designated as safety issue: No ]
    Duration of disease control according to RECIST v1.1.
  • Progression Free Survival (PFS) [ Time Frame: From the first administration of study medication to the time of disease progression or death ] [ Designated as safety issue: No ]
    Progression-free survival was defined as the time from the first administration of study medication to the time of disease progression or death, whichever occurred first.
  • Overall Survival (OS) [ Time Frame: From the first administration of study medication to the time of death ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the first administration of study medication to the time of death from any cause.
  • Area Under the Concentration-time Curve (AUC) Tau,ss of Afatinib [ Time Frame: PK samples were taken at hours; 167:55, 479:55, 481:05, 482:05, 483:05, 485:05, 487:05 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 ] [ Designated as safety issue: No ]
    Area under the concentration-time curve of Afatinib in plasma over a uniform dosing interval t at steady state.
  • Cmax,ss of Afatinib [ Time Frame: PK samples were taken at hours; 167:55, 479:55, 481:05, 482:05, 483:05, 485:05, 487:05 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 ] [ Designated as safety issue: No ]
    Maximum concentration of Afatinib in plasma at steady state.
  • AUC 0-tz of Gemcitabine [ Time Frame: PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 ] [ Designated as safety issue: No ]
    Area under the concentration-time curve of Gemcitabine in plasma over the time interval from 0 up to the last quantifiable data point
  • Cmax of Gemcitabine [ Time Frame: PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 ] [ Designated as safety issue: No ]
    Maximum concentration of Gemcitabine in plasma.
  • Total Clearance (CL) of Gemcitabine [ Time Frame: PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 ] [ Designated as safety issue: No ]
    Total Clearance (CL) of Gemcitabine from plasma.
  • Volume of Distribution at Steady State (Vss) of Gemcitabine [ Time Frame: PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3 ] [ Designated as safety issue: No ]
    Apparent volume of distribution at steady state (Vss) of Gemcitabine.
  • AUC 0-24 of Docetaxel [ Time Frame: PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 ] [ Designated as safety issue: No ]
    Area under the concentration-time curve of docetaxel in plasma over the time interval from 0 up to 24 hours
  • Cmax of Docetaxel [ Time Frame: PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 ] [ Designated as safety issue: No ]
    Maximum concentration of docetaxel in plasma.
  • Total Clearance (CL) of Docetaxel [ Time Frame: PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 ] [ Designated as safety issue: No ]
    Total Clearance (CL) of Docetaxel from plasma.
  • Volume of Distribution at Steady State (Vss) of Docetaxel [ Time Frame: PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55 ] [ Designated as safety issue: No ]
    Apparent volume of distribution at steady state (Vss) of Docetaxel.
  • Secondary objectives are : To assess the safety of the combination [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  • Secondary objectives are: To investigate the PK characteristics of docetaxel or gemcitabine and of oral Afatinib in the tested treatment schedule [ Time Frame: 23 days ] [ Designated as safety issue: No ]
  • Secondary objectives are: To assess antitumor activity [ Time Frame: Until progression ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Phase I Dose Escalation Trial of Afatinib Plus Gemcitabine or Plus Docetaxel
A Phase I Dose Escalation Trial of Once Daily Oral Treatment Using Afatinib (BIBW2992) Plus Gemcitabine or Docetaxel in Patients With Relapsed or Refractory Solid Tumors.

To establish the maximum tolerated dose (MTD) of oral afatinib (BIBW2992) given in combination with gemcitabine or docetaxel in patients with relapsed or refractory tumors.

To assess the safety of the combination. To investigate the PK characteristics of docetaxel or gemcitabine and of oral afatinib (BIBW2992) in the tested treatment schedule. To assess antitumor activity.

Not Provided
Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:
Pharmacokinetic samples
Non-Probability Sample
solid tumors
Neoplasms
  • Drug: Afatinib
    Maximum Tolerated Dose of Afatinib in combination with gemcitabine
  • Drug: docetaxel
    Maximum Tolerated Dose of Afatinib in combination with docetaxel
  • Drug: gemcitabine
    Maximum Tolerated Dose of Afatinib in combination with gemcitabine
  • Afatinib and docetaxel
    Interventions:
    • Drug: Afatinib
    • Drug: docetaxel
  • Afatinib and gemcitabine
    Interventions:
    • Drug: Afatinib
    • Drug: gemcitabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
94
April 2015
April 2015   (final data collection date for primary outcome measure)

Inclusion criteria:

1. histologically or cytologically confirmed diagnosis of any advanced or metastatic relapsed or refractory solid tumor.

Exclusion criteria:

  1. Active brain metastases
  2. Patients with known pre-existing interstitial lung disease
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT01251653
1200.93, 2010-020560-37
Not Provided
Not Provided
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP