Dose Escalation Study of BIBW 2992 in Patients With Advanced Solid Tumors

NCT02171663 | Completed Phase 1

• 1 other identifier: 1200.2
• Study Type: interventional
• Target: 43
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective was the assessment of safety of BIBW 2992 as assessed by the maximum tolerated dose (MTD). Secondary objectives were collection of overall safety data, antitumor efficacy data, as well as the determination of pharmacokinetics and the pharmacodynamic modulation of biomarkers by BIBW 2992.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  up to 22 months

• Incidence and intensity of Adverse Events (AE) according to Common Terminology Criteria (CTC Version 3), that were associated with increasing doses of BIBW 2992

  up to 22 months

Secondary Outcomes (15)

• Assessment of biomarker modulation (EGFR, p-EGFR, p-MAPK (mitogen-activated protein kinase), p-Akt, Ki 67, p-27KIP1) in skin biopsies

  Baseline and day 21 of the first treatment period

• Assessment of biomarker modulation (EGFR, p-EGFR, Her2, p-MAPK, p-Akt, Ki 67, p-27KIP1) in tumor biopsies in six or more patients treated at the MTD

  Baseline and day 21 of the first treatment period

• Objective tumor responses

  up to 22 months

• Correlation of EGFR, HER2, estrogen receptor (ER) and progesterone receptor (PrR) immunohistochemical status, based on tumor biopsies or excisions obtained prior to this trial, with objective tumor responses

  up to 22 months

• Area under the plasma concentration time curve (AUC) for different time points

  up to 72 hours after last dose on day 21

Study Arms (1)

BIBW 2992

EXPERIMENTAL

Drug: BIBW 2992

Interventions

BIBW 2992 DRUG

BIBW 2992

Eligibility Criteria

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

You may qualify if:

• Male or female patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumors, of types historically known to express EGFR and/or HER2, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment preferably patients with breast, colorectal or prostate cancer
• Age 18 years or older
• Life expectancy of at least three (3) months
• Written informed consent given that is consistent with International Conference on Harmonization - Good Clinical Practice guidelines
• Eastern Cooperative Oncology Group (ECOG) performance score 0, 1, or 2
• Patients must have resolution of prior chemo-, hormone, immuno-, or radiotherapy-related toxicities to CTC Grade \<= 1 or baseline
• Patients have to be recovered from previous surgery
• The 12 additional patients recruited at the MTD must also meet the following criteria:
• Measurable tumor deposits (RECIST) by one or more techniques (X-ray, CT, MRI)

You may not qualify if:

• Active infectious disease
• Gastrointestinal disorders that might interfere with the absorption of the study drug or chronic diarrhea
• Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
• Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least eight weeks, no history of cerebral edema or bleeding in the past eight weeks and no requirement for steroids or anti-epileptic therapy
• Cardiac left ventricular function with resting ejection fraction ≥ CTC Grade 1
• Absolute neutrophil count (ANC) less than 1500 / mm3
• Platelet count less than 100 000 / mm3
• Bilirubin greater than 1.5 mg / dl (\> 26 μmol / L, SI unit equivalent)
• Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than three times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
• Serum creatinine greater than 1.5 mg / dl (\> 132 μmol / L, SI (Système Internationale) unit equivalent)
• Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
• Pregnancy or breast-feeding
• Treatment with other investigational drugs; chemotherapy, immunotherapy, radiotherapy or hormone therapy (excluding Luteinizing Hormone-Releasing Hormone agonists, other hormones taken for breast cancer, or bisphosphonates) or participation in another clinical study within the past four weeks before start of therapy or concomitantly with this study
• Treatment with an EGFR- or HER2 inhibiting drug within the past four weeks before start of therapy or concomitantly with this study (8 weeks for trastuzumab)
• Patients unable to comply with the protocol

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Neoplasms

Interventions

Afatinib

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: June 20, 2014
• First Posted: June 24, 2014
• Study Start: March 1, 2004
• Primary Completion: February 1, 2006
• Last Updated: January 28, 2015

Record last verified: 2015-01