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

NCT01169675 | Completed Phase 1 Results

• 1 other identifier: 1200.92
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 2

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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (5)

• Investigator Defined Dose Limiting Toxicity (DLT) During All Courses of Treatment, Treated Set

  DLT were assessed during all cycles of treatment

• Objective Response (OR)

  Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

• Disease Control

  Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

• Progression Free Survival (PFS)

  Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

• Tumour Shrinkage

  Every 6 weeks before week 48 and every 12 weeks after week 48 until progression

Study Arms (6)

BIBW 2992 low dose

EXPERIMENTAL

patient receives low dose tablet BIBW 2992 po daily plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle

Drug: BIBW 2992 low dose; Drug: pemetrexed

BIBW 2992 medium dose

EXPERIMENTAL

patient receives medium dose BIBW 2992 po daily plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle

Drug: pemetrexed; Drug: BIBW 2992 medium dose

BIBW 2992 high dose

EXPERIMENTAL

patient receives high dose BIBW 2992 po daily plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle

Drug: BIBW 2992 high dose; Drug: pemetrexed

BIBW 2992 low dose 6 day

EXPERIMENTAL

patient receives low dose BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle

Drug: pemetrexed; Drug: BIBW 2992 low dose 6 day

BIBW 2992 medium dose 6 day

EXPERIMENTAL

patient receives medium BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle

Drug: pemetrexed; Drug: BIBW 2992 medium dose 6 day

BIBW 2992 high dose 6 day

EXPERIMENTAL

patient receives high dose BIBW 2992 po daily on days 1-6 plus pemetrexed 500mg/m\^2 on day 1 of 21 day cycle

Drug: BIBW 2992 high dose 6 day; Drug: pemetrexed

Interventions

BIBW 2992 low dose DRUG

patient receives low dose BIBW 2992 po daily on day 1 of 21 day cycle

BIBW 2992 low dose

BIBW 2992 high dose DRUG

patient receives high dose BIBW 2992 po daily on day 1 of 21 day cycle

BIBW 2992 high dose

pemetrexed DRUG

given intravenously on day 1 of a 21 day cycle

BIBW 2992 medium dose

BIBW 2992 high dose 6 day DRUG

patient receives high dose BIBW 2992 po daily on days 1-6 on 1 of 21 day cycle

BIBW 2992 high dose 6 day

BIBW 2992 low dose 6 day DRUG

patient receives low dose BIBW 2992 po daily on days 1-6 on day 1 of 21 day cycle

BIBW 2992 low dose 6 day

BIBW 2992 medium dose 6 day DRUG

patient receives medium dose BIBW 2992 po daily on day1 to 6 of a 21 day cycle

BIBW 2992 medium dose 6 day

BIBW 2992 medium dose DRUG

patient receives medium dose BIBW 2992 po daily on day 1 of 21 day cycle

BIBW 2992 medium dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (2)

1200.92.1001 Boehringer Ingelheim Investigational Site

Edmonton, Alberta, Canada

Location

1200.92.1002 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Location

Related Publications (1)

• 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.

  PMID: 25037863 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Afatinib; Pemetrexed

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2010
• First Posted: July 26, 2010
• Study Start: July 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: June 9, 2014
• Results First Posted: December 20, 2013

Record last verified: 2014-01

Locations

CA (2)