Clinical trial NCT01206816: An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 (Volasertib)in Combination With Oral BIBW 2992 (Afatinib) in Patients With Advanced Solid Tumours
Official title: An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 in Combination With Oral BIBW 2992 in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-09-22
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: The primary objective of the current study is to investigate the Maximum Tolerated Dose (MTD) in terms of safety and tolerability of the combination of BI 6727 with BIBW 2992, in patients with advanced or metastatic solid tumours. Dosages of both BI 6727 and BIBW 2992 will be varied to establish the MTD of the combination. Two combination treatment schedules will be tested, the MTD of each combination will be determined.

Secondary objectives are the exploration of pharmacokinetics, overall safety and preliminary efficacy.


Eligibility criteria: Inclusion criteria:

* Patients with histologically or cytologically confirmed diagnosis of advanced, non resectable and/or metastatic, relapsed or refractory solid tumours not amenable to standard therapy and for whom no therapy of proven efficacy exists
* Eastern Cooperative Oncology Group performance score 0 - 2
* Recovery from clinically significant toxicities from previous systemic anti-cancer therapies or radiotherapy

Exclusion criteria:

* Serious illness, concomitant non-oncological disease or mental problem considered by the investigator to be incompatible with participation to the trial
* Known hypersensitivity to the trial drugs or their excipients
* Treatment with any other investigational drug or active participation in any other interventional trial within 28 days before first administration of trial drug(s) or concomitantly with this trial
* Major surgery or radiotherapy within 28 days before start of therapy or concomitantly with this trial
* Systemic anti-cancer therapy within 28 days before start of therapy or concomitantly with this trial
* Requirements for treatment with any of the prohibited concomitant medications
* Active infectious disease or known HIV I/II infection
* Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea
* Active brain metastases
* History or presence of cardiovascular abnormalities deemed clinically relevant by the investigator
* Cardial left ventricular function with resting ejection fraction \< 50%
* Inadequate hepatic, renal and haematologic organ function
* QT prolongation deemed clinically relevant by the investigator
* Active alcohol or drug abuse
* Women of childbearing potential and men who are able to father a child unwilling to use a medically acceptable method of contraception during the trial and 28 days thereafter
* Pregnancy or breast-feeding
* Patients unable to comply with the protocol
* Patients with known pre-existing interstitial lung disease

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLT)
timeFrame: 22 Days
measure: Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib.
timeFrame: MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days)
Secondary outcomes:
measure: Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0
timeFrame: After the first drug administration until 28 days after the last drug administration, up to 413 days.
measure: Number of Patients With Objective Response (OR)
timeFrame: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).
measure: Number of Patients With Best Overall Response.
timeFrame: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).
measure: Number of Patients With Disease Control
timeFrame: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: 1230.20.32001 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1230.20.32003 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1230.20.32002 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Machiels JP, Peeters M, Herremans C, Surmont V, Specenier P, De Smet M, Pilz K, Strelkowa N, Liu D, Rottey S. A phase I study of volasertib combined with afatinib, in advanced solid tumors. Cancer Chemother Pharmacol. 2015 Oct;76(4):843-51. doi: 10.1007/s00280-015-2860-2. Epub 2015 Sep 8.