Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Paclitaxel

Fluorouracil

Albumin-Bound Paclitaxel

Cisplatin

Afatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

daily oral dose of BIBW 2992 combined with 3-weekly infusion of cisplatin-paclitaxel

daily oral dose of BIBW 2992 combined with 3-weekly infusion of cisplatin-5FU

In each arm, BIBW 2992 dose will be escalated to determine MTD. Starting dose will be 20mg daily followed by 40 mg (with the option of an intermediary dose of 30 mg) then 50mg daily. Dose escalation will stop at 50 mg. No intra patient dose escalation.

BIBW 2992

Boehringer Ingelheim

Study to determine the maximum tolerated dose of BIBW 2992 when combined with backbone chemotherapies consisting in cisplatin plus paclitaxel or cisplatin plus 5 FU.

The overall safety, the pharmacokinetics and the anti-tumour efficacy will also be assessed.

Study to Determine the Maximum Tolerated Dose of BIBW 2992 (Afatinib) When Combined With Cisplatin/Paclitaxel or Cisplatin/5-FU in Patients With Advanced Solid Tumours

A Phase Ib Open Label Study to Assess the Safety, Tolerability and Pharmacokinetics of Continuous Dosing With BIBW 2992 Combined With Two Different Regimens of Backbone Chemotherapy: Cisplatin Combined With 5 Fluorouracil and Cisplatin Combined With Paclitaxel in Patients With Advanced Solid Tumors.

Number of participants with DLT in the first cycle (21 days) for the determination of the MTD.

The MTD was determined using a standard 3 +3 dose escalation cohort design. The sample size and the number of patients who receive each dose in this design depends on the frequency of DLT at each dose level in cycle 1.

Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.0. Objective response is defined as complete response (CR) and partial response (PR).

Cmax,ss represents the maximum concentration of afatinib in plasma at steady state

Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m\^2 and Cisplatin 50mg/m\^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Pac175 + Cis50 + Afatinib20

Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m\^2 and Cisplatin 75mg/m\^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Pac175 + Cis75 + Afatinib20

Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m\^2 and Cisplatin 75mg/m\^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Pac175 + Cis75 + Afatinib30

Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m\^2 and Cisplatin 75mg/m\^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Pac175 + Cis75 + Afatinib40

Patients received continous daily dosing with Afatinib 50mg film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel 175mg/m\^2 and Cisplatin 75mg/m\^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Pac175 + Cis75 + Afatinib50

Patients received continous daily dosing with Afatinib 20mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m\^2 and Cisplatin 75mg/m\^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Cis75 + 5FU750 + Afatinib20

Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m\^2 and Cisplatin 75mg/m\^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Cis75 + 5FU750 + Afatinib30

Patients received continous daily dosing with Afatinib 40mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m\^2 and Cisplatin 75mg/m\^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Cis75 + 5FU750 + Afatinib40

Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 750mg/m\^2 and Cisplatin 100mg/m\^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Cis100 + 5FU750 + Afatinib30

Patients received continous daily dosing with Afatinib 30mg film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil 1000mg/m\^2 and Cisplatin 100mg/m\^2 on day 1 of each cycle. Treatment until disease progression or toxicity.

Cis100 + 5FU1000 + Afatinib30

Total

Age, Continuous

Sex: Female, Male

Boehringer Ingelheim Call Center

Treated Set (TS) - TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib.

Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

Maximum tolerated dose - Afatinib

Maximum tolerated dose - Cisplatin

Maximum tolerated dose - Pac (A) or 5-FU (B)

Patients received continous daily dosing with Afatinib film-coated tablets over 21 day treatment cycles and infusions of Paclitaxel and Cisplatin on day 1 of each cycle in 5 dose levels as outlined in first primary endpoint.

Pac + Cis + Afatinib (Regimen A)

Patients received continous daily dosing with Afatinib film-coated tablets over 21 day treatment cycles and infusions of 5-Fluorouracil and Cisplatin on day 1 of each cycle in 5 dose levels as outlined in first primary endpoint.

5FU + Cis + Afatinib (Regimen B)

Maximum Tolerated Dose (MTD) for Regimen A and Regimen B

Number of Patients With Objective Response

The pharmacokinetic analysis set includes all patients who took at least one dose of trial medication and provided at least one blood sample following drug administration. Values were excluded from descriptive statistics when a comparison with plasma concentrations in the same treatment group was impossible.

Spots Global Cancer Trial Database for Study to Determine the Maximum Tolerated Dose of BIBW 2992 (Afatinib) When Combined With Cisplatin/Paclitaxel or Cisplatin/5-FU in Patients With Advanced Solid Tumours

Trial Identification

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Interventions

Study Description

Keywords

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