Clinical trial NCT00730821: Phase I of BIBW 2992/BIBF 1120 Combination Therapy in Solid Tumors
Official title: A Combination Phase I Open Label Dose Escalation Study of Concomitant Administration of BIBW 2992 With BIBF 1120 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: 2008-08-08
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to determine the MTD of the combination of BIBW 2992/BIBF 1120 therapy administered concomitantly in a 28-day cycle schedule.

Secondary objectives are the collection of antitumor efficacy data, the determination of pharmacokinetic parameters of BIBF 1120 and BIBW 2992, and if data allow the determination of the pharmacokinetic influence of BIBW 2992 on BIBF 1120 and vice versa.


Eligibility criteria: Inclusion Criteria:

1. Male or female patients with confirmed diagnosis of advanced, non-resectable and/or metastatic solid tumors, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment.
2. Age 18 years or older.
3. Life expectancy of at least three (3) months.
4. Written informed consent that is consistent with ICH-GCP guidelines.
5. Eastern Cooperative Oncology Group performance score 0, 1or 2.
6. Patients recovered from any therapy-related toxicities from previous chemo-,hormone-, immuno-, or radiotherapies to CTC \<= Grade 1.
7. Patients must have 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 diarrhea.
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 edema 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 \<50%.
6. Absolute neutrophil count (ANC) less than 1500/mm3.
7. Platelet count less than 100,000/mm3.
8. Bilirubin greater than 1.5 mg/dl (\>26 ¿mol /L, SI unit equivalent).
9. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than two and a half times the upper limit of normal (2.5 X ULN ).
10. Serum creatinine greater than 1.5 mg/dl (\>132 ¿mol/L, SI unit equivalent).
11. Women and men who are 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, radiotherapy or hormone therapy (including LHRH agonists, megestrol acetate, or other hormones taken for breast cancer or prostate cancer); participation in another clinical study within the past 4 weeks before start of therapy or concomitantly with this study. Treatment with bisphosphonates is allowed.
14. Treatment with an EGFR- or HER2 inhibiting drug within the past 4 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.
17. Patients who require therapeutic anticoagulation or antiplatelet therapy \[except treatment with Aspirin (Acetylsalicylic Acid)\].
18. Patients with history of haemorrhagic or thrombotic events (including transient ischemic attacks) in the past 12 months. Known inherited predisposition to bleeding or thrombosis.

Primary outcomes:
measure: The primary endpoint of this trial is the safety of the combination of BIBW 2992/BIBF 1120 when administered concomitantly, and this is assessed by the dose limiting toxicity
timeFrame: Until undue toxicity or progressive disease.
Secondary outcomes:
measure: Pharmacokinetics, Objective tumor response.
timeFrame: Until undue toxicity or progressive disease.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: 1239.1.3 Boehringer Ingelheim Investigational Site
state: Arizona
city: Tampa
country: United States
facility: 1239.1.1 Boehringer Ingelheim Investigational Site
state: Florida
city: Detroit
country: United States
facility: 1239.1.2 Boehringer Ingelheim Investigational Site
state: Michigan
city: Omaha
country: United States
facility: 1239.1.4 Boehringer Ingelheim Investigational Site
state: Nebraska
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: