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

Boehringer Ingelheim

Status and phase

Completed

Phase 1

Conditions

Neoplasms

Treatments

Drug: BIBW 2992

Study type

Interventional

Funder types

Industry

Identifiers

NCT02171663

1200.2

Details and patient eligibility

About

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.

Enrollment

43 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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)

Exclusion criteria

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
Active alcohol or drug abuse

The patient may be eligible for re-treatment after the previous course finished. The patient will not be eligible if the following criteria are met:

Patients with clinical signs of disease progression or if latest X-ray, CT or MRI reveals progressive disease
Cardiac left ventricular function CTC Grade ≥ 2 at any time during the previous course
Patients fulfilling any of the Exclusion Criteria as mentioned before on Day 29 of the previous course
Patients not recovered from any dose-limiting toxicity (DLT) 14 days after the last administration of BIBW 2992 in the previous course. Recovery is defined as a return to baseline level or CTC Grade 1, whichever is higher