Clinical trial NCT00716417: 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
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-07-16
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
timeFrame: 21 days
measure: Maximum Tolerated Dose (MTD) for Regimen A and Regimen B
timeFrame: 21 days
Secondary outcomes:
measure: Number of Patients With Objective Response
timeFrame: Tumor assessment were performed at screening and every 2nd cycle until end of follow up (=end of treatment + 30 days +/- 7 days)
measure: Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)
timeFrame: 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
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: 1200.37.3202 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1200.37.3201 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1200.37.3203 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: