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

Neoplasms Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00716417
• Other study ID #: 1200.37
• Secondary ID: 2008-002613-43
• Status: Completed
• Phase: Phase 1
• First received: July 15, 2008
• Last updated: June 3, 2014
• Start date: July 2008

Study information

• Verified date: August 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Patients with histologically or cytologically confirmed diagnosis of non resectable and / or metastatic cancer, preferably squamous cell carcinomas of head and neck, oesophagus, lung or cervix

2. Indication for a standard treatment with either cisplatin plus paclitaxel or cisplatin plus 5 FU as judged by the investigator

3. Age 18 years or older.

4. Life expectancy of at least three (3) months.

5. Written informed consent that is consistent with ICH-GCP guidelines.

6. Eastern Cooperative Oncology Group (ECOG) performance score less or equal 2.

7. Patients must have recovered from any therapy-related toxicity from previous chemo-, hormone-, immuno-, or radiotherapies.

8. Patients recovered from previous surgery.

Exclusion criteria:

1. Active infectious disease.

2. Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea.

3. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.

4. Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least four (4) weeks, no history of cerebral oedema or bleeding in the past four (4) weeks and no requirement for steroids or anti-epileptic therapy.

5. Cardiac left ventricular function with resting ejection fraction less than 50%

6. Absolute neutrophil count (ANC) less than 1500 / mm3.

7. Platelets count less than 100 000/mm3.

8. Bilirubin more than 1.5 x upper limit of institutional norm.

9. Aspartate amino transferase (AST) or alanine amino transferase (ALT) more than 3 x upper limit of institutional norm.

10. Serum creatinine more than 1.5 x upper limit of institutional norm.

11. Women and men sexually active and unwilling to use a medically acceptable method of contraception.

12. Pregnancy or breast-feeding.

13. Treatment with other investigational drugs; chemotherapy, immunotherapy, or radiotherapy or participation in another clinical study with anti-cancer therapy within the past 4 weeks before start of therapy or concomitantly with this study.

14. Treatment with an EGFR- or HER2 inhibiting drug within the past four weeks before start of therapy or concomitantly with this study (2 weeks for trastuzumab).

15. Patients unable to comply with the protocol.

16. Active alcohol or drug abuse.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• BIBW 2992
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
low to high dose, daily

Locations

Country	Name	City	State
Belgium	1200.37.3202 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1200.37.3201 Boehringer Ingelheim Investigational Site	Edegem
Belgium	1200.37.3203 Boehringer Ingelheim Investigational Site	Gent

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)	Number of participants with DLT in the first cycle (21 days) for the determination of the MTD.	21 days	No
Primary	Maximum Tolerated Dose (MTD) for Regimen A and Regimen B	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.	21 days	No
Secondary	Number of Patients With Objective Response	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).	Tumor assessment were performed at screening and every 2nd cycle until end of follow up (=end of treatment + 30 days +/- 7 days)	No
Secondary	Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)	Cmax,ss represents the maximum concentration of afatinib in plasma at steady state	0.05hours (h) before administration and 1h, 2h, 2h 55 minutes (min), 4h, 4h 30min, 5h, 6h, 8h, 10h, 24h, 48h, 216h, 480h after administration	No

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