Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 (Afatinib) Plus Sirolimus (Rapamune®) in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib

NCT00993499 | Completed Phase 1 Results

• 2 other identifiers: 1200.702009-010432-18
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 8

Brief Summary

The primary objective of this trial is to identify the Maximum Tolerated Dose of BIBW 2992 therapy when given continuously in combination with Sirolimus. The MTD will be based on the Dose Limiting Toxicity information collected during the first two cycles. Overall safety, pharmacokinetics and anti-tumour efficacy will be evaluated as secondary objectives.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Occurrence of Dose Limiting Toxicities (DLT)

  Number of participants with of dose limiting toxicities (DLT)

  2 first cycles, 56 days

Secondary Outcomes (11)

• Best Overall Response

  From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

• Objective Response

  From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

• Rate of Disease Control

  From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

• Exploratory Examination of EGFR Mutations (Exons 19, 20 and 21 and Others) in Serum/Plasma DNA and Tumour DNA.

  Multiple time points during the trial

• Maximum Measured Plasma Concentration of Afatinib at Steady State (Cmax,ss)

  24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib

Study Arms (1)

BIBW 2992 + Sirolimus

EXPERIMENTAL

Dose escalation of the combination BIBW 2992 plus Sirolimus.

Drug: BIBW 2992; Drug: Sirolimus (rapamycin)

Interventions

BIBW 2992 DRUG

Dose escalation (19-40 patients): low or high dose oral + 12 addit. pat. at MTD, until progression or undue AEs

BIBW 2992 + Sirolimus

Sirolimus (rapamycin) DRUG

Dose escalation (19-40 patients): several dose levels + 12 addit. pat. at MTD until progression or undue AEs.

BIBW 2992 + Sirolimus

Eligibility Criteria

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

You may qualify if:

• Pathologically or cytologically confirmed diagnosis of Stage IIIB or Stage IV NSCLC
• Patients who have failed conventional treatment (at least 1 prior treatment line), or for whom no therapy of proven efficacy exists
• Patients whose tumors:
• are EGFR mutation-positive or
• are EGFR mutation-negative or unknown provided they had disease progression after achieving either response or stable disease for at least 6 months from a previous treatment with erlotinib (Tarceva®) or gefitinib (Iressa®)
• Patients aged 18 years or older
• Life expectancy of at least three (3) months
• Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0-2
• Written informed consent that is consistent with ICH-GCP guidelines

You may not qualify if:

• Prior major surgery, chemotherapy or radiation therapy within 4 weeks before start of therapy.
• Prior treatment with an mTOR inhibitor within the past 4 weeks before start of therapy or concomitantly with this study
• Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of run-in treatment with Sirolimus
• Active CNS metastases (defined as stable for \<4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants or steroids)
• Severe alteration in serum fasting cholesterol (equal or more than 350 mg/dL) or triglycerides (equal or more than 400 mg/dL). Patients may be allowed to enrol on the trial after initiation of lipid lowering agents.
• Requirement for treatment with any of the prohibited concomitant medications:
• Concomitant CYP3A4 inhibitors within the past 7 days before start of therapy or concomitantly with this study.
• Concomitant CYP3A4 inducers within the past 14 days before start of therapy or concomitantly with this study.
• Any contraindications for therapy with Sirolimus.
• Known hypersensitivity to BIBW 2992, Sirolimus or other rapamycin analogues (everolimus, temsirolimus, deforolimus, etc.) or the excipients of any of the trial drugs.
• Use of any investigational drug within 4 weeks before start of therapy.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (8)

1200.70.34001 Boehringer Ingelheim Investigational Site

Badalona (Barcelona), Spain

Location

1200.70.34008 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1200.70.34009 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1200.70.34006 Boehringer Ingelheim Investigational Site

Girona, Spain

Location

1200.70.34007 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat (Barcelona), Spain

Location

1200.70.34005 Boehringer Ingelheim Investigational Site

Majadahonda (Madrid), Spain

Location

1200.70.34004 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

1200.70.34002 Boehringer Ingelheim Investigational Site

Zaragoza, Spain

Location

Related Publications (1)

• Moran T, Palmero R, Provencio M, Insa A, Majem M, Reguart N, Bosch-Barrera J, Isla D, Costa EC, Lee C, Puig M, Kraemer S, Schnell D, Rosell R. A phase Ib trial of continuous once-daily oral afatinib plus sirolimus in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer and/or disease progression following prior erlotinib or gefitinib. Lung Cancer. 2017 Jun;108:154-160. doi: 10.1016/j.lungcan.2017.03.009. Epub 2017 Mar 22.

  PMID: 28625629 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib; Sirolimus

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; Macrolides; Lactones

Results Point of Contact

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

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2009
• First Posted: October 12, 2009
• Study Start: October 1, 2009
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 7, 2015
• Results First Posted: October 7, 2015

Record last verified: 2015-09

Locations

ES (8)