Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Gemcitabine

Docetaxel

Afatinib

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Maximum Tolerated Dose of Afatinib in combination with gemcitabine

Maximum Tolerated Dose of Afatinib in combination with docetaxel

docetaxel

gemcitabine

Boehringer Ingelheim

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.

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.

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 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 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 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. 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.

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 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.

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 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 of Afatinib in plasma over a uniform dosing interval t at steady state.

Maximum concentration of Afatinib in plasma at steady state.

Area under the concentration-time curve of Gemcitabine in plasma over the time interval from 0 up to the last quantifiable data point

Maximum concentration of Gemcitabine in plasma.

Total Clearance (CL) of Gemcitabine from plasma.

Apparent volume of distribution at steady state (Vss) of Gemcitabine.

Area under the concentration-time curve of docetaxel in plasma over the time interval from 0 up to 24 hours

Maximum concentration of docetaxel in plasma.

Total Clearance (CL) of Docetaxel from plasma.

Apparent volume of distribution at steady state (Vss) of Docetaxel.

Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course.

Afatinib 30mg and Gemcitabine 1000mg

Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course.

Afatinib 30mg and Gemcitabine 1250mg

Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course.

Afatinib 40mg and Gemcitabine 1000mg

Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course.

Afatinib 40mg and Gemcitabine 1250mg

Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Gemcitabine 1250 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course.

Afatinib 50mg and Gemcitabine 1250mg

Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 60 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course.

Afatinib 30mg and Docetaxel 60mg

Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course.

Afatinib 30mg and Docetaxel 75mg

Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course.

Afatinib 40mg and Docetaxel 75mg

Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course.

Afatinib 50mg and Docetaxel 75mg

Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Docetaxel 60 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course

Total

Age, Continuous

Sex: Female, Male

Treated Set (TS): The Treated Set consists of all patients who received at least one application of the trial drug.

Boehringer Ingelheim, Call Center

Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD).

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

The Incidence and Intensity of AEs With Grading According to CTCAE.

Complete response (CR)

Partial response

Stable disease/ Non-CR/Non-PD

Progressive disease (PD)

Not evaluable

Missing

Best Overall Response According to RECIST v1.1 Criteria

Disease Control According to RECIST v1.1

Objective Response According to RECIST v1.1

6 Weeks

12 Weeks

24 Weeks

Not applicable

Time to Objective Response According to RECIST v1.1

TS for patients who experienced objective response.

Duration of Objective Response According to RECIST v1.1

TS for patients who experienced disease control.

Duration of Disease Control According to RECIST v1.1

Progression Free Survival (PFS)

Overall Survival (OS)

Afatinib 40mg With Gemcitabine 1000 mg

Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in 3- week treatment course.

Afatinib 40mg Without Gemcitabine

Afatinib 30mg With Docetaxel 60mg

Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in 3- week treatment course.

Afatinib 30mg Without Docetaxel 60mg

Afatinib 30mg With Docetaxel 75mg

Afatinib 30mg Without Docetaxel 75mg

The Pharmacokinetic Set (PKS) was a subset of the Treated Set that included all patients who had taken at least 1 dose of study medication and for whom at least 1 valid plasma concentration was available.

Area Under the Concentration-time Curve (AUC) Tau,ss of Afatinib

Cmax,ss of Afatinib

Gemcitabine 1000mg With Afatinib 40 mg

Gemcitabine 1000 mg/m2 administered as intravenous infusion on Days 1 and 8 of each 3- week treatment course.

Gemcitabine 1000mg Without Afatinib

AUC 0-tz of Gemcitabine

Cmax of Gemcitabine

Total Clearance (CL) of Gemcitabine

Volume of Distribution at Steady State (Vss) of Gemcitabine

Docetaxel 60mg With Afatinib 30mg

Docetaxel 60 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course.

Docetaxel 60mg Without Afatinib

Docetaxel 75mg With Afatinib 30mg

Docetaxel 75 mg/m2 administered as intravenous infusion on Day 1 of each 3- week treatment course.

Spots Global Cancer Trial Database for A Phase I Dose Escalation Trial of Afatinib Plus Gemcitabine or Plus Docetaxel

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial