Clinical trial NCT01169675: BIBW 2992 (Afatinib) in Combination With Pemetrexed in Advanced Solid Tumours
Official title: BIBW 2992 Phase I Combination With Pemetrexed in Advanced Solid Tumours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-07-26
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This Phase I study will investigate the safety of BIBW 2992 in combination with standard dose pemetrexed (500mg/m2) given on a 21 day cycle in patients with advanced solid cancers. BIBW 2992 will be given on two different dose schedules; dosing on days 1-21 and dosing on days 1 to 6 of a 21 day cycle.

The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), including BIBW 2992 have demonstrated efficacy in solid tumors including non-small cell lung cancer (NSCLC). In addition, pemetrexed has demonstrated efficacy and has been approved as single agent chemotherapy in second-line NSCLC patients with adenocarcinoma. The data obtained from this trial shall allow for a conclusion as to whether BIBW 2992 may be safely administered in advanced cancer patients in combination therapy with pemetrexed.


Eligibility criteria: Inclusion criteria:

1. Age 18 or older.
2. Eastern cooperative oncology group performance status of 0-2.
3. Life expectancy of at least 12 weeks.
4. Measurable disease according to Response evaluation criteria in solid tumors 1.1 criteria.
5. Written informed consent

Exclusion criteria:

1. Treatment with an investigational drug within the past 28 days prior to the start of therapy
2. Persisting toxicities which are clinically significant from previous therapy
3. Patients who are unwilling or unable to take folic acid and vitamin B12 supplementation
4. Active brain metastases
5. Other active malignancy diagnosed within the past 3 years
6. Concomitant intercurrent illnesses that would limit compliance with trial requirement
7. Patients unable or unwilling to interrupt concomitant administration of Non-steroidal anti-inflammatory drugs (NSAIDS) as per pemetrexed prescribing information
8. Patients who have received prior therapy with BIBW 2992
9. Left ventricular function by echocardiogram or Multiple gated acquisition scan (MUGA) less than institutional lower limit of normal
10. Absolute neutrophil count (ANC) less than 1,500/mm3
11. Platelet count less than 100,000/mm3
12. Hemoglobin less than 90g/L
13. Total bilirubin less than 26µmol/L
14. Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) greater than 2.5 X ULN, except in case of known liver metastasis where maximum 5 X ULN is acceptable
15. Serum creatinine level greater than 133µmol/L and/or creatinine clearance (measured or calculated) less than 45 ml/min
16. History or recent gastrointestinal bleeding, obstruction or perforation or malabsorption syndrome and must be able to swallow the BIBW 2992 in whole by mouth.
17. History of interstitial lung disease
18. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
19. Pregnancy or breast feeding
20. Known or suspected active alcohol or drug abuse
21. Patients unable to comply with the protocol
22. Has a diagnosis of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
23. Any known hypersensitivity to the trial drugs or their excipients

Primary outcomes:
measure: Investigator Defined Dose Limiting Toxicity (DLT) During First Course of Treatment, Treated Set
timeFrame: DLT were assessed during the first cycle (days 1-21)
Secondary outcomes:
measure: Investigator Defined Dose Limiting Toxicity (DLT) During All Courses of Treatment, Treated Set
timeFrame: DLT were assessed during all cycles of treatment
measure: Objective Response (OR)
timeFrame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression
measure: Disease Control
timeFrame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression
measure: Progression Free Survival (PFS)
timeFrame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression
measure: Tumour Shrinkage
timeFrame: Every 6 weeks before week 48 and every 12 weeks after week 48 until progression
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: 1200.92.1001 Boehringer Ingelheim Investigational Site
state: Alberta
city: Hamilton
country: Canada
facility: 1200.92.1002 Boehringer Ingelheim Investigational Site
state: Ontario
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Chu QS, Sangha R, Hotte SJ, Sergenson G, Schnell D, Chand VK, Hirte HW. A phase I, dose-escalation trial of continuous- and pulsed-dose afatinib combined with pemetrexed in patients with advanced solid tumors. Invest New Drugs. 2014 Dec;32(6):1226-35. doi: 10.1007/s10637-014-0139-9. Epub 2014 Jul 19.