Phase 1
Completed N=53
BIBW 2992 (Afatinib) in Combination With Pemetrexed in Advanced Solid Tumours
Neoplasms
Source: ClinicalTrials.gov NCT01169675 ↗
Enrolled (actual)
53
Serious AEs
41.5%
Results posted
Dec 2013
Primary outcomePrimary: Investigator Defined Dose Limiting Toxicity (DLT) During First Course of Treatment, Treated Set — 6; 2; 1; 6 participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Investigator Defined Dose Limiting Toxicity (DLT) During First Course of Treatment, Treated Set |
6; 2; 1; 6; 4 | — |
| SECONDARY Investigator Defined Dose Limiting Toxicity (DLT) During All Courses of Treatment, Treated Set |
11; 2; 3; 11; 4 | — |
| SECONDARY Objective Response (OR) |
2; 0; 0; 2; 0 | — |
| SECONDARY Disease Control |
6; 1; 3; 6; 2 | — |
| SECONDARY Progression Free Survival (PFS) |
2.49; 2.52; 2.56; 2.52; 2.69 | — |
| SECONDARY Tumour Shrinkage |
10; 2; 3; 5; 1; 2 | — |
Eligibility Criteria
Inclusion criteria
- Age 18 or older.
- Eastern cooperative oncology group performance status of 0-2.
- Life expectancy of at least 12 weeks.
- Measurable disease according to Response evaluation criteria in solid tumors 1.1 criteria.
- Written informed consent
Exclusion criteria
- Treatment with an investigational drug within the past 28 days prior to the start of therapy
- Persisting toxicities which are clinically significant from previous therapy
- Patients who are unwilling or unable to take folic acid and vitamin B12 supplementation
- Active brain metastases
- Other active malignancy diagnosed within the past 3 years
- Concomitant intercurrent illnesses that would limit compliance with trial requirement
- Patients unable or unwilling to interrupt concomitant administration of Non-steroidal anti-inflammatory drugs (NSAIDS) as per pemetrexed prescribing information
- Patients who have received prior therapy with BIBW 2992
- Left ventricular function by echocardiogram or Multiple gated acquisition scan (MUGA) less than institutional lower limit of normal
- Absolute neutrophil count (ANC) less than 1,500/mm3
- Platelet count less than 100,000/mm3
- Hemoglobin less than 90g/L
- Total bilirubin less than 26µmol/L
- 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
- Serum creatinine level greater than 133µmol/L and/or creatinine clearance (measured or calculated) less than 45 ml/min
- History or recent gastrointestinal bleeding, obstruction or perforation or malabsorption syndrome and must be able to swallow the BIBW 2992 in whole by mouth.
- History of interstitial lung disease
- Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
- Pregnancy or breast feeding
- Known or suspected active alcohol or drug abuse
- Patients unable to comply with the protocol
- Has a diagnosis of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
- Any known hypersensitivity to the trial drugs or their excipients
Data sourced from ClinicalTrials.gov (NCT01169675). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.