BIBW 2992 After Administration of Docetaxel in Patients With Advanced Solid Tumors

A Phase I Open-label Dose Escalation Study of Single Oral Daily Doses of BIBW 2992 for Three Days After Administration of Docetaxel, in Patients With Advanced Solid Tumors

Maximum tolerated dose (MTD), safety, pharmacokinetic and pharmacodynamic parameters, and efficacy of pulsatile administration of BIBW 2992 in combination with docetaxel (Taxotere®)

Inclusion Criteria:

• Male or female patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumors, of types historically known to express EGFR and/or HER2, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment preferably patients with breast, prostate, or ovarian cancer. In addition, patients with a disease amenable for standard treatment with docetaxel
• Age 18 years or older
• Life expectancy of at least three (3) months
• Written informed consent that is consistent with International Conference on Harmonization - Good Clinical Practice guidelines
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
• Patients recovered (Common Terminology Criteria (CTC) Grade 0 or 1) from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies
• Patients recovered from previous surgery

The 12 additional patients recruited at the MTD must also meet the following criteria:

• Measurable tumor deposits (Response Evaluation Criteria in Solid Tumors) by one or more techniques (X-ray, CT, MRI) and/or recognized tumor markers such as prostate specific antigen (prostate cancer) or cancer antigen 125 (Ovarian cancer)

Exclusion Criteria:

• Active infectious disease
• Gastrointestinal disorders that might interfere with the absorption of the study drug or chronic diarrhea
• Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
• 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 eight weeks, no history of cerebral edema or bleeding in the past eight weeks and no requirement for steroids or anti-epileptic therapy
• Cardiac left ventricular function with resting ejection fraction CTC ≥ Grade 1
• Absolute neutrophil count (ANC) less than 1500 / mm3
• Platelet count less than 100 000 / mm3
• Bilirubin > upper limit of normal (ULN)
• Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) > 1.5 x ULN
• Alkaline Phosphatase > 2.5 x ULN
• Serum creatinine > 1.5 mg / dl (> 132 μmol / L, SI (Système Internationale) unit equivalent)
• Women and men sexually active and unwilling to use a medically acceptable method of contraception
• Pregnancy or breast-feeding
• Treatment with other investigational drugs; chemotherapy, immunotherapy, radiotherapy or hormone therapy (excluding luteinising hormone-releasing hormone agonists, other hormones taken for breast cancer, or bisphosphonates) or participation in another clinical study within the past four weeks before start of therapy or concomitantly with this study
• Treatment with an EGFR- or HER2 inhibiting drug within the past four weeks before start of therapy or concomitantly with this study (8 weeks for trastuzumab)
• Patients unable to comply with the protocol
• Active alcohol or drug abuse
• Hypersensitivity to docetaxel or any component or other drug formulated with polysorbate 80

The patient may be eligible for re-treatment after the previous course is finished. The patient will not be eligible if any of the following conditions are met:

• If patients latest X-ray, CT or MRI reveals progressive disease, or if clinical assessment reveals signs of disease progression
• Cardiac left ventricular function CTC Grade ≥ 2 at any time during the previous course
• Patients fulfilling any of the Exclusion Criteria listed before as determined on day 18 of the treatment course 1 (visit 7) or day 18 (visit R5) of the previous course
• Patients not recovered from any dose-limiting toxicity (DLT) 14 days after onset. Recovery is defined as a return to baseline level or CTC Grade <= 1, whichever is higher