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
Condition: Neoplasms
Intervention: BIBW 2992; BIBW 2992
Intervention description: 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.; low to high dose, daily
Intervention MeSH terms: Afatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.