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

NCT01206816 | Completed Phase 1 Results

• 2 other identifiers: 1230.202010-019437-97
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 3

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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLT)

  MTD was defined on the basis of DLTs occuring during Cycle 1 of the dose escalation part in each of the 2 treatment schedules. DLTs were defined as drug related based on Common Terminology Criteria for AE's (CTCAE) Grade(G) :1) G4 neutropenia (ANC, including bands, \<500/mm³) for more than 7 days, 2) G3 or 4 neutropenia associated with fever \>38.5° C (febrile neutropenia),3) Neutropenic infection G ≥3, 4) G4 thrombocytopenia or G3 thrombocytopenia associated with bleeding requiring whole blood transfusion.5) Non-haematological G ≥3 toxicity excluding: (a) untreated G3 diarrhoea, (b) untreated G3 nausea and/or vomiting, (c) untreated G3 rash. 6) G2 increase in AST and/or ALT in conjunction with an elevated bilirubin level of G ≥2, 7) G2 nausea and/or vomiting despite optimal supportive/antiemetic treatment for at least 7consecutive days. 8) G2 diarrhoea for 2 or more consecutive days despite antidiarrhoeal medication/hydration, 9) Decrease in left ventricular function G ≥2.

  22 Days

• Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib.

  Maximum Tolerable Dose (MTD) was determined by dose escalation for volasertib and afatinib. The "3 + 3 design with de-escalation" for both the Schedules A and B. Patients were sequentially allocated to the dose cohorts. Apart from allocation to the treatment schedules, escalation and/or de-escalation to determine the MTD occurred independently within the 2 dose schedules. Cohorts of 3 patients were to be treated at the starting dose levels according to the treatment schedule. Before entering patients at a higher dose level, all patients at the previous dose level combination had to complete at least the initial cycle of 21 days.

  MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days)

Secondary Outcomes (4)

• Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0

  After the first drug administration until 28 days after the last drug administration, up to 413 days.

• Number of Patients With Objective Response (OR)

  Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

• Number of Patients With Best Overall Response.

  Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

• Number of Patients With Disease Control

  Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

Study Arms (1)

two experimental arms

EXPERIMENTAL

patients receive increasing doses of BI 6727 in combination with increasing doses of BIBW 2992

Drug: BI 6727 + BIBW 2992

Interventions

BI 6727 + BIBW 2992 DRUG

BI 6727 administered i.v. every 21 days + BIBW 2992 given orally once a day

two experimental arms

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

1230.20.32001 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1230.20.32003 Boehringer Ingelheim Investigational Site

Edegem, Belgium

Location

1230.20.32002 Boehringer Ingelheim Investigational Site

Ghent, Belgium

Location

Related Publications (1)

• 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.

  PMID: 26349473 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

BI 6727; Afatinib

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

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

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: September 22, 2010
• Study Start: October 4, 2010
• Primary Completion: November 15, 2012
• Study Completion: November 15, 2012
• Last Updated: February 1, 2019
• Results First Posted: February 1, 2019

Record last verified: 2018-08

Locations

BE (3)