Clinical trial NCT01251653: A Phase I Dose Escalation Trial of Afatinib Plus Gemcitabine or Plus Docetaxel
Official title: 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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-12-02
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: solid tumors

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD).
timeFrame: 3 weeks
Secondary outcomes:
measure: The Incidence and Intensity of AEs With Grading According to CTCAE.
timeFrame: From first drug administration until 28 days after last drug administration, up to 717 days.
measure: Best Overall Response According to RECIST v1.1 Criteria
timeFrame: From first drug administration until 28 days after last drug administration, up to 717 days.
measure: Disease Control According to RECIST v1.1
timeFrame: From first drug administration until 28 days after last drug administration, up to 717 days.
measure: Objective Response According to RECIST v1.1
timeFrame: From first drug administration until 28 days after last drug administration, up to 717 days.
measure: Time to Objective Response According to RECIST v1.1
timeFrame: 6 weeks, 12 weeks and 24 weeks
measure: Duration of Objective Response According to RECIST v1.1
timeFrame: From the first documented complete response or partial response to the time of disease progression or death
measure: Duration of Disease Control According to RECIST v1.1
timeFrame: From the first administration of study medication to the time of disease progression or death
measure: Progression Free Survival (PFS)
timeFrame: From the first administration of study medication to the time of disease progression or death
measure: Overall Survival (OS)
timeFrame: From the first administration of study medication to the time of death
measure: Area Under the Concentration-time Curve (AUC) Tau,ss of Afatinib
timeFrame: 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
measure: Cmax,ss of Afatinib
timeFrame: 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
measure: AUC 0-tz of Gemcitabine
timeFrame: 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
measure: Cmax of Gemcitabine
timeFrame: 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
measure: Total Clearance (CL) of Gemcitabine
timeFrame: 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
measure: Volume of Distribution at Steady State (Vss) of Gemcitabine
timeFrame: 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
measure: AUC 0-24 of Docetaxel
timeFrame: 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
measure: Cmax of Docetaxel
timeFrame: 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
measure: Total Clearance (CL) of Docetaxel
timeFrame: 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
measure: Volume of Distribution at Steady State (Vss) of Docetaxel
timeFrame: 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
Other outcomes:
Locations:
city: Dijon
country: France
facility: 1200.93.33002 Boehringer Ingelheim Investigational Site
city: Saint-Herblain cedex
country: France
facility: 1200.93.33001 Boehringer Ingelheim Investigational Site
city: Toulouse
country: France
facility: 1200.93.33003 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Hiret S, Isambert N, Gomez-Roca C, Bennouna J, Sassi M, de Mont-Serrat H, Fan J, Schnell D, Delord JP. Phase I dose-escalation trial of afatinib, an irreversible ErbB family blocker, in combination with gemcitabine or docetaxel in patients with relapsed or refractory solid tumors. Invest New Drugs. 2018 Dec;36(6):1044-1059. doi: 10.1007/s10637-018-0601-1. Epub 2018 May 29.