BIBW 2992 (Afatinib) in Combination With Pemetrexed in Advanced Solid Tumours

Neoplasms Clinical Trial

Official title:

BIBW 2992 Phase I Combination With Pemetrexed in Advanced Solid Tumours

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01169675
• Other study ID #: 1200.92
• Status: Completed
• Phase: Phase 1
• First received: July 19, 2010
• Last updated: June 3, 2014
• Start date: July 2010
• Est. completion date: November 2012

Study information

• Verified date: January 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• BIBW 2992 low dose
patient receives low dose BIBW 2992 po daily on day 1 of 21 day cycle
• BIBW 2992 high dose
patient receives high dose BIBW 2992 po daily on day 1 of 21 day cycle
• pemetrexed
given intravenously on day 1 of a 21 day cycle
• pemetrexed
given intravenously on day 1 of a 21 day cycle
• BIBW 2992 high dose 6 day
patient receives high dose BIBW 2992 po daily on days 1-6 on 1 of 21 day cycle
• pemetrexed
given intravenously on day 1 of a 21 day cycle
• pemetrexed
given intravenously on day 1 of a 21 day cycle
• pemetrexed
given intravenously on day 1 of a 21 day cycle
• pemetrexed
given intravenously on day 1 of a 21 day cycle
• BIBW 2992 low dose 6 day
patient receives low dose BIBW 2992 po daily on days 1-6 on day 1 of 21 day cycle
• BIBW 2992 medium dose 6 day
patient receives medium dose BIBW 2992 po daily on day1 to 6 of a 21 day cycle
• BIBW 2992 medium dose
patient receives medium dose BIBW 2992 po daily on day 1 of 21 day cycle

Locations

Country	Name	City	State
Canada	1200.92.1001 Boehringer Ingelheim Investigational Site	Edmonton	Alberta
Canada	1200.92.1002 Boehringer Ingelheim Investigational Site	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigator Defined Dose Limiting Toxicity (DLT) During First Course of Treatment, Treated Set	Occurence of DLT during the first course of treatment to determine the maximum tolerated dose (MTD) of Afatinib at two different dose schedules in combination with the standard established dose of pemetrexed (500 mg/m2).	DLT were assessed during the first cycle (days 1-21)	No
Secondary	Investigator Defined Dose Limiting Toxicity (DLT) During All Courses of Treatment, Treated Set	Occurence of DLT during all courses of treatment with Afatinib at two different dose schedules in combination with the standard established dose of pemetrexed (500 mg/m2).	DLT were assessed during all cycles of treatment	No
Secondary	Objective Response (OR)	Objective Response is defined as complete response or partial response according to the response evaluation criteria in solid tumours (RECIST) version 1.1.; Complete Response (CR): disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR): at least 30% decrease of the sum of longest diameter (LD) of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of LD of target lesions together with an absolute increase in the sum of LD of at least 5 millimeters; Stable Disease (SD): neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD.	Every 6 weeks before week 48 and every 12 weeks after week 48 until progression	No
Secondary	Disease Control	Disease Control is defined as complete response, partial response, or stable disease according to the response evaluation criteria in solid tumours (RECIST) version 1.1.	Every 6 weeks before week 48 and every 12 weeks after week 48 until progression	No
Secondary	Progression Free Survival (PFS)	PFS was defined as the time from the first treatment to the occurence of tumour progression or death, whichever came first. It was assessed according to RECIST version 1.1 criteria.	Every 6 weeks before week 48 and every 12 weeks after week 48 until progression	No
Secondary	Tumour Shrinkage	Tumour shrinkage is defined as the maximum percentage decrease from baseline in the sum of the longest diameters of target lesions.	Every 6 weeks before week 48 and every 12 weeks after week 48 until progression	No

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