BIBW 2992 Plus Simvastatin vs. BIBW 2992 in Previously Treated Patients With Advanced Non-adenocarcinomatous NSCLC

NCT01156545 | Completed Phase 2

• 2 other identifiers: NCCCTS-10-489BIBW 2992 1200.113
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesized that simvastatin may enhance sensitivity to BIBW 2992 in non-adenocarcinoma that is relatively resistant to TKIs. Based on these data, the investigators will research the effectiveness comparing BIBW2992, an irreversible EGFR-TKI, plus simvastatin with BIBW2992 alone in the setting of a randomized phase II study in previously treated patients with advanced non-adenocarcinomatous non-small cell lung cancer (NSCLC).

Conditions

Non-small Cell Lung Cancer

Keywords

BIBW 2992; Simvastatin; NSCLC; advanced stage; previously treated patients; non-adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Repeat tumor assessments will be performed after the completion of Week 4, Week 8, and in 8-week intervals thereafter until progression or withdrawal for another reason

  each 8 weeks

Secondary Outcomes (5)

• Disease Control Rate

  every 8 weeks

• Progression-Free Survival

  every 8 weeks

• Overall Survival

  every 12 weeks

• Adverse event

  first drug intake until 28 days after last treatment administration

• Pharmacogenetic and biomarkers analyses

  every 8 weeks

Study Arms (2)

Treatment arm

EXPERIMENTAL

BIBW 2992 plus simvastatin arm

Drug: BIBW 2992; Drug: simvastatin

control arm

ACTIVE COMPARATOR

BIBW 2992 arm

Drug: BIBW 2992

Interventions

BIBW 2992 DRUG

BIBW 2992 40mg, once a day, oral intake, every day

Also known as: afatinib

Treatment arm; control arm

simvastatin DRUG

simvastatin 40mg, once a day, oral intake, every day.

Also known as: simvastar

Treatment arm

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed diagnosis of Stage IIIB or Stage IV non-adenocarcinomatous non-small cell lung cancer (e.g., squamous cell or large cell carcinoma).(The 7th edition of the TNM classification for lung cancer47-See Appendix 6)
• Progressive disease following the first or second line cytotoxic chemotherapy regimen(s) including at least one platinum-containing regimen.
• Measurable disease according to RECIST 1.1.40
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2.41
• Age ≥ 18 years.
• Life expectancy of at least three (3) months.
• Written informed consent that is consistent with ICH-GCP guidelines.

You may not qualify if:

• More than three (3) prior cytotoxic chemotherapy treatment regimen for relapsed or metastatic NSCLC.
• Prior treatment with EGFR targeting small molecules or antibodies (e.g., gefitinib, erlotinib, cetuximab).
• Chemotherapy, hormonal therapy (other than megestrol acetate or steroids required for maintenance non-cancer therapy), immunotherapy or surgery (other than biopsy) within 4 weeks prior to study entry.
• Radiotherapy within 2 weeks prior to study entry. Only palliative radiotherapy to non-target lesion should be allowed for the entered cases.
• Active brain metastases with clinically significant neurological symptoms or signs. Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs.
• Any other current malignancy or malignancy diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer).
• Known pre-existing interstitial lung disease.
• Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption or CTC grade ≥2 diarrhea of any etiology.
• Absolute neutrophil count (ANC) \<1500 / mm3.
• Platelet count \< 100,000 / mm3.
• Serum creatinine \>1.5 times upper limit of normal (ULN) or creatinine clearance \< 60 ml / min
• Bilirubin \> 1.5 times upper limit of normal.
• Aspartate amino transferase (AST) or alanine amino transferase (ALT) \> 3 times the upper limit of normal (ULN) (if related to liver metastases \> 5 times ULN).
• History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to study entrance.
• Cardiac left ventricular function with resting ejection fraction of less than 50%.

Sponsors & Collaborators

• National Cancer Center, Korea: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

National Cancer Center

Goyang-si, Gyeonggi-do, 410-769, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib; Simvastatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• JI-YOUN HAN, M.D. PhD.

  National Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Center for Lung Cancer

Study Record Dates

• First Submitted: July 2, 2010
• First Posted: July 5, 2010
• Study Start: October 1, 2010
• Primary Completion: December 31, 2016
• Study Completion: June 9, 2021
• Last Updated: April 6, 2022

Record last verified: 2022-04

Locations

KR (1)