Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Paclitaxel

Albumin-Bound Paclitaxel

Afatinib

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

patient to receive tablets of BIBW 2992 once a day, starting at high dose until progression of the disease

patient whose disease progressed on treatment with BIBW 2992 monotherapy to receive tablet of BIBW 2992 once a day in combination with i.v. paclitaxel 3 weekly

BIBW2992

tablet BIBW 2992 in combination with i.v. paclitaxel 3 weekly

BIBW2992 + paclitaxel

Boehringer Ingelheim

The primary objective of this open-label, single arm Phase II trial is to explore the efficacy of BIBW 2992 defined by the objective response rate (CR, PR) as determined by the RECIST criteria, in patients with advanced NSCLC Stage IIIB or IV whose tumours harbour activating mutations within exon 18 to exon 21 of the EGFR receptor, in patients with mutations in the HER2/neu receptor and in patients with EGFR FISH positive tumours with no EGFR mutations.

Single-arm Trial of BIBW 2992 (Afatinib) in Demographically and Genotypically Selected NSCLC Patients

A Phase II Single-arm Trial of BIBW 2992 in Demographically and Genotypically Selected NSCLC

Percentage of participants with best objective response: confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0.

Percentage of participants with OR or stable disease (SD) as determined by RECIST version 1.0.

PFS time defined as time from the start of treatment to the earliest of progression (RECIST), clinical progression (investigator), start of new anti-cancer treatment or death.

Pre-dose Concentrations of Afatinib in Plasma at Steady State on Days 15, 29 and 57 (Cpre,ss,15, Cpre,ss,29 and Cpre,ss,57)

Afatinib 50mg film coated tablets were administered once daily as long as they were tolerated by patients, until disease progression (according to the response evaluation criteria in solid tumors)

Afatinib 50mg

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.

Percentage of Participants With Best Objective Response

Percentage of Participants With Disease Control (DC)

Progression Free Survival (PFS) Time

Cpre,ss,15 (N=13)

Cpre,ss,29 (N=12)

Cpre,ss,57 (N=5)

Patients with no data available for the relevant parameter and dose were excluded from analysis.

Summary of Pre-dose Concentrations of Afatnib in Plasma

Overall Study

Bevacizumab

Carboplatin

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Part A and B:80mg/m2 given on Day 1, 8 and 15 of 28 Day cycle.

BIBW 2992

Escalating dose Cohorts - 5mg / kg, 7.5mg / kg and 10mg / kg given Day 1 and Day 15 of a 28 days cycle

The main purpose of this study is to assess the optimum dose of the following medications when they are given together:

* BIBW 2992 and paclitaxel (Taxol)
* BIBW 2992 and paclitaxel and bevacizumab (Avastin)
* BIBW 2992 and carboplatin
* BIBW 2992 and paclitaxel and carboplatin The effect of the different drug combinations will also be assessed.

Trial Exploring Afatinib (BIBW 2992) + Paclitaxel (Part A), Afatinib + Paclitaxel + Bevacizumab (Part B), Afatinib + Carboplatin (Part C) and Afatinib+ Paclitaxel +Carboplatin(Part D) in Patients With Advanced Solid Tumours

A Phase I Open Label Trial of Continuous Dosing With BIBW 2992 Combined With Paclitaxel and BIBW 2992 Combined With Paclitaxel and Bevacizumab, BIBW 2992 Combined With Carboplatin and BIBW 2992 Combined With Paclitaxel and Carboplatin in Patients With Advanced Solid Tumours

Dose limiting toxicity (DLT) was defined as an Adverse Event (AE) or laboratory abnormality considered as related to study treatment.

The MTD of afatinib in selected combination treatments was defined as the highest dose at which no more than 1 out of 6 patients experienced DLTs during the first treatment cycle, i.e. the highest dose with a DLT incidence ≤17%. The MTD was determined separately for Afatinib in combination with Paclitaxel (part A), Afatinib in combination with Paclitaxel and Bevacizumab (part B), Afatinib and Carboplatin (part C), and Afatinib in combination with Paclitaxel and Carboplatin (part D).

In part C, dose escalation was not continued beyond the dose level A40C6, due to safety and pharmacokinetic considerations and upon mutual agreement between the investigators and the sponsor. Formally, no MTD was determined, however a recommended phase II dose was determined and is presented here.

0=not maximum tolerated dose, 1=is maximum tolerated dose

Note, the depicted order of treatment groups is driven by dose level, not by the actual dosing steps.

Incidence and Intensity of AEs (Adverse Events) graded according to the maximum CTCAE (Common Toxicity Criteria for Adverse Events) grade based on the number of patients with AEs with CTCAE Grade 1-5.

Area under the concentration-time curve of Afatinib in plasma at steady state.

Maximum measured concentration of Afatinib in plasma at steady state.

AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours.

Maximum measured concentration of Paclitaxel in plasma.

Bevacizumab plasma concentration after infusion of Bevacizumab 5mg/kg after end of 1st and 2nd infusion in Cycle 1.

AUCt,ss: Area under the concentration-time curve of Afatinib in plasma at steady state.

AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours.

Maximum measured concentration of Carboplatin in plasma.

AUCt,ss: Area under the concentration-time curve of Afatinib at steady state.

AUC0-23: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 23 hours.

Number of subjects with objective tumour response (unconfirmed).

Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR).

Number of subjects with confirmed objective tumour response.

Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR). Objective response was to be confirmed by a second tumour assessment at least 4 weeks after the assessment of CR or PR.

Afatinib (film-coated tablet) 20 mg qd (once daily) was administered orally in combination with Paclitaxel 80 mg/m2 administered as intravenous infusion on Days 1, 8, and 15 of a 28-day cycle.

Part A: A20P80 (Afatinib + Paclitaxel)

Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Paclitaxel 80 mg/m2 administered as intravenous infusion on Days 1, 8, and 15 of a 28-day cycle.

Part A: A40P80 (Afatinib + Paclitaxel)

Afatinib (film-coated tablet) 50 mg qd (once daily) was administered orally in combination with Paclitaxel 80 mg/m2 administered as intravenous infusion on Days 1, 8, and 15 of a 28-day cycle.

Part A: A50P80 (Afatinib + Paclitaxel)

Afatinib (film-coated tablet) 20 mg qd (once daily) was administered orally in combination with Paclitaxel 80 mg/m2 administered as intravenous infusion on Days 1, 8 and 15 and Bevacizumab 5mg/kg administered as intravenous infusion on Days 1 and 15 of a 28-day cycle.

Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)

Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Paclitaxel 80 mg/m2 administered as intravenous infusion on Days 1, 8 and 15 and Bevacizumab 5mg/kg administered as intravenous infusion on Days 1 and 15 of a 28-day cycle.

Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)

Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Paclitaxel 80 mg/m2 administered as intravenous infusion on Days 1, 8 and 15 and Bevacizumab 5mg/kg administered as intravenous infusion on Days 1 and 15 of a 28-day cycle.

Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)

Afatinib (film-coated tablet) 20 mg qd (once daily) was administered orally in combination with Paclitaxel 80 mg/m2 administered as intravenous infusion on Days 1, 8 and 15 and Bevacizumab 7.5 mg/kg administered as intravenous infusion on Days 1 and 15 of a 28-day cycle.

Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)

Afatinib (film-coated tablet) 20 mg qd (once daily) was administered orally in combination with Paclitaxel 80 mg/m2 administered as intravenous infusion on Days 1, 8 and 15 and Bevacizumab 10 mg/kg administered as intravenous infusion on Days 1 and 15 of a 28-day cycle.

Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)

Afatinib (film-coated tablet) 20 mg qd (once daily) administered orally in combination with Carboplatin (intravenous infusion) at a dose targeting an AUC (Area Under the Concentration-time curve) of 6 mg/mL min (AUC6) administered on Day 1 of a 21-day cycle.

Part C: A20C6 (Afatinib + Carboplatin)

Afatinib (film-coated tablet) 40 mg qd (once daily) administered orally in combination with Carboplatin (intravenous infusion) at a dose targeting an AUC (Area Under the Concentration-time curve) of 6 mg/mL min (AUC6) administered on Day 1 of a 21-day cycle.

Part C: A40C6 (Afatinib + Carboplatin)

Afatinib (film-coated tablet) 20 mg qd (once daily) was administered orally in combination with Carboplatin AUC5 (intravenous infusion) and Paclitaxel 175 mg/m2 (intravenous infusion) which were administered on Day 1 of a 21-day cycle.

Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)

Afatinib (film-coated tablet) 30 mg qd (once daily) was administered orally in combination with Carboplatin AUC5 (intravenous infusion) and Paclitaxel 175 mg/m2 (intravenous infusion) which were administered on Day 1 of a 21-day cycle.

Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)

Afatinib (film-coated tablet) 40 mg qd (once daily) was administered orally in combination with Carboplatin AUC5 (intravenous infusion) and Paclitaxel 175 mg/m2 (intravenous infusion) which were administered on Day 1 of a 21-day cycle.

Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)

Afatinib (film-coated tablet) 20 mg qd (once daily) was administered orally in combination with Carboplatin AUC6 (intravenous infusion) and Paclitaxel 175 mg/m2 (intravenous infusion) which were administered on Day 1 of a 21-day cycle.

Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)

Total

Treated Set: Patients who received at least 1 dose of study treatment were included in the treated set.

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

Maximum Tolerated Dose (MTD)

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Incidence and Intensity of AEs According to the Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade

Part A: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15

Part A: Afatinib Cmax,ss on Day 15

Day 1 (N=3, 6, 5)

Day 15 (N=3, 6, 5)

Part A: AUC0-24: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From Zero Extrapolated to 24 Hours on Day 1 and Day 15

Day 1

Day 15

Part A: Paclitaxel Cmax on Day 1 and Day 15

Part B: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15

Part B: Afatinib Cmax,ss on Day 15

Part B: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours on Day 1 and Day 15

Part B: Paclitaxel Cmax on Day 1 and Day 15

Dose escalation of Bevacizumab administered as intravenous infusion to 5 mg/kg. Bevacizumab administered on Days 1 and 15 of a 28-day cycle.

Part B: End of 1st Infusion of Cycle 1

Part B: End of 2nd Infusion of Cycle 1

Part B: Bevacizumab Plasma Concentration

Part C: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State in Cycle 2

Part C: Afatinib Cmax,ss in Cycle 2

Cycle 1 (N=3, 9)

Cycle 2 (N=3, 6)

Part C: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2

Part C: Carboplatin Cmax in Cycle 1 and Cycle 2

Part D: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State.

Part D: Afatinib Cmax,ss

Cycle 1 (N=5, 7, 5, 6)

Cycle 2 (N=8, 5, 2, 4)

Part D: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 23 Hours in Cycle 1 and Cycle 2

Part D: Paclitaxel Cmax in Cycle 1 and 2

Cycle 1 (N=5, 7, 5, 7)

Cycle 2 (N=8, 5, 2, 5)

Part D: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2

Part D: Carboplatin Cmax in Cycle 1 and 2

Objective response: No

Objective response: Yes

Objective Tumour Response (Unconfirmed)

Objective Tumour Response (Confirmed)

Talcum powder 4 g + Afatinib 0,4 g. Is entered once

Used Afatinib particles of which had an average size of 22 μm and a volume concentration of small particles (\<5 μm) - only 19%

Used Talcum powder particles of which had an average size of 24.5 μm and a volume concentration of small particles (\<5 μm) - only 11%

Talcum powder

In non-small cell lung cancer and metastases in the pleural cavity, pathological effusion is formed.

Currently, the most common and effective method of obliteration of the pleural cavity is pleurodesis with talcum powder.

Talc, when it surface of the pleura, causes chemical inflammation that leads to the soldering of the lungs and chest wall. As a result, the liquid ceases to accumulate.

The addition of a therapeutic dose of afatinib to talc not only blocks effusion into the pleural cavity, but also reduces tumor and metastatic processes.

The proposed procedure for dry pleurodesis consists of one stage.

Talc is introduced into the pleural cavity in several ways:

* Drainage - a tube is inserted into the pleural cavity through a puncture in the chest, and then a pasty talcum is delivered into the cavity, which spreads through the cavity during the change of the patient's body position.
* Talcum powder - under the control of thoracoscopy, dry talc is blown into the pleural cavity of the patient, which allows him to evenly distribute and significantly increases the effectiveness of the procedure.

In this Clinical Trial investigators will use the method of thoracoscopy - the blow in of talcum powder and therapeutic dose of Afatinib. Before injection, a suspension of talc and afatinib is subjected to the procedure of pharmaceutical mixing.

The operation is well tolerated by participants and lasts no more than 30 minutes. The effectiveness of the method is 90%.

Dry Pleurodesis With Talcum and Afatinib is Used to Treat Patients With Non-Small Cell Lung Carcinoma

New Method of Treatment for Thoracoscopy or Bronchoscopy by Suspension of Fine Powder of Talcum and Afatinib is Used in Patients With Positive Mutation of EGFR in Non-Small Cell Lung Carcinoma (NSCLC)

Evaluation of the effectiveness of the dry pleurodesis procedure in combination with talc and afatinib with the introduction of a powder suspension through a thoracoscope.

The assessment is performed by CT (computed tomography) of each participant twice: 30 days from the day of the procedure and 90 days later.

Center Trials & Treatment

Center Trials & Treatment Europe

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma, Squamous Cell

Esophageal Neoplasms

Recurrence

Esophageal Squamous Cell Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

International Nonproprietary Name (INN): BIBW 2992 Pharmacological dosage form: Film-coated tablet Supplier: Boehringer Ingelheim Pharma GmbH \& Co. KG Unit content: 40 mg, 30 mg, 20 mg film-coated tablet (BIBW 2992 content in film-coated tablet is related with equivalent free base BIBW 2992.) Daily dose: 40 mg Dosing period: To be successively administered once daily until a disease will develop, an unacceptable adverse event will occur, or another reason requiring discontinuation of the study will occur; For administration, study treatment consists of periods(each 4 weeks(28 days)).

Route of administration: Orally (Take by swallowing) Dosage: Once daily

As a 2nd generation EGFR-TKI that irreversibly binds to EGFR receptors, afatinib showed the possibility of superior effects to 1st generation TKIs such as erlotinib and gefitinib. In a phase III study LUX-lung 3 in patients with EGFR mutation-positive non-small-cell lung cancer, afatinib monotherapy showed longer progression-free disease survival time of 11.1 months than that (6.9 months) of pemetrexed/cisplatin combination therapy. Based on such the results, it is currently recommended as the standard first-line treatment for EGFR mutation-positive lung cancer, and clinical studies are also being actively conducted in other types of carcinomas characterized by EGFR gene mutation and overexpression. Thirty (30) solid cancer patients were included in a phase I trial of afatinib, and of them, a patient with esophageal cancer had partial response. Taken together, based upon the results from clinical trials of afatinib conducted so far, 7 out of 15 esophageal cancer patients achieved clinical responses of 3 months or longer.

Hence, the overall results from previous studies of gefitinib and erlotinib as EGFR TKIs and our study of dacomitinib, as well as from preceding studies of afatinib - a 2nd generation EGFR TKI - suggest the possibility of an effective therapy in esophageal cancer characterized by well-known EGFR overexpression. In this phase II trial, afatinib shall be administered to patients with squamous cell carcinoma of esophagus to evaluate its effects and toxicity. Also, biomarkers to predict responses to afatinib shall be explored through further studies.

A Phase II Trial of Afatinib in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of Esophagus

Yonsei University

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

During RT: 75 mg/m2 daily , 4 weeks after RT: given days 1 to 5 of 28 day cycles (150 mg/m2 in cycle 1, 200 mg/m2 in cycle 2 up to cycle 6)

Radiotherapy

Escalating dose cohorts during Radiotherapy(RT) period, fixed dose after RT

Escalating dose cohorts during Radiotherapy(RT) period , fixed dose after RT

This study is a phase I, open label trial to determine the Maximum Tolerated Dose (MTD), safety, pharmacokinetics, and efficacy of BIBW 2992 (an epidermal growth factor receptor(EGFR)inhibitor) to be used in combination with:

* radiotherapy alone (in patients with an unmethylated (functioning) MGMT gene regulator) or
* radiotherapy and Temozolomide (in patients with a methylated (silenced) O6-methylguanine-DNA methyltransferase gene (MGMT) to treat newly diagnosed patients with Grade IV Glioblastoma (primary brain cancer).

Open Label Trial to Explore Safety of Combining Afatinib (BIBW 2992) and Radiotherapy With or Without Temozolomide in Newly Diagnosed Glioblastoma Multiform

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Single-arm Trial of BIBW 2992 (Afatinib) in Demographically and Genotypically Selected NSCLC Patients	NCT00730925	Carcinoma, Non-...	BIBW2992 BIBW2992 + pacl...	18 Years -	Boehringer Ingelheim
Trial Exploring Afatinib (BIBW 2992) + Paclitaxel (Part A), Afatinib + Paclitaxel + Bevacizumab (Part B), Afatinib + Carboplatin (Part C) and Afatinib+ Paclitaxel +Carboplatin(Part D) in Patients With Advanced Solid Tumours	NCT00809133	Neoplasms	Paclitaxel Carboplatin BIBW 2992 Paclitaxel BIBW2992 Paclitaxel Carboplatin Bevacizumab BIBW 2992 BIBW 2992	18 Years -	Boehringer Ingelheim
Dry Pleurodesis With Talcum and Afatinib is Used to Treat Patients With Non-Small Cell Lung Carcinoma	NCT03827070	Non Small Cell ...	Afatinib Talcum powder	21 Years - 40 Years	Center Trials & Treatment Europe
Single-arm Trial of BIBW 2992 (Afatinib) in Demographically and Genotypically Selected NSCLC Patients	NCT00730925	Carcinoma, Non-...	BIBW2992 BIBW2992 + pacl...	18 Years -	Boehringer Ingelheim
Dry Pleurodesis With Talcum and Afatinib is Used to Treat Patients With Non-Small Cell Lung Carcinoma	NCT03827070	Non Small Cell ...	Afatinib Talcum powder	21 Years - 40 Years	Center Trials & Treatment Europe
Trial Exploring Afatinib (BIBW 2992) + Paclitaxel (Part A), Afatinib + Paclitaxel + Bevacizumab (Part B), Afatinib + Carboplatin (Part C) and Afatinib+ Paclitaxel +Carboplatin(Part D) in Patients With Advanced Solid Tumours	NCT00809133	Neoplasms	Paclitaxel Carboplatin BIBW 2992 Paclitaxel BIBW2992 Paclitaxel Carboplatin Bevacizumab BIBW 2992 BIBW 2992	18 Years -	Boehringer Ingelheim
A Phase II Trial of Afatinib in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of Esophagus	NCT02353936	Squamous Cell C...	BIBW2992	20 Years -	Yonsei University
Open Label Trial to Explore Safety of Combining Afatinib (BIBW 2992) and Radiotherapy With or Without Temozolomide in Newly Diagnosed Glioblastoma Multiform	NCT00977431	Glioblastoma	Temozolomide Radiotherapy BIBW2992 Radiotherapy BIBW2992	18 Years - 69 Years	Boehringer Ingelheim
Research of Biomarkers of Activity and Efficacy of BIBW2992 in Untreated Non-metastatic HNSCC Patients	NCT01415674	Carcinoma, Squa...	Afatinib	18 Years -	UNICANCER
A Phase II Trial of Afatinib in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of Esophagus	NCT02353936	Squamous Cell C...	BIBW2992	20 Years -	Yonsei University

Spots Global Cancer Trial Database for bibw2992

Every month we try and update this database with for bibw2992 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bibw2992

Every month we try and update this database with for bibw2992 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bibw2992 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.