An Dose Escalation Trial of Oral BIBF 1120 in Combination With Intravenous Vinorelbine in Elderly Patients With Advanced Non Small Lung Cell Cancer - Stage IV (VENUS-1)

NCT01684111 | Completed Phase 1

• 2 other identifiers: ABC-2011-NSCLC-052011-003094-28
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 4

Brief Summary

To investigate the maximum tolerated dose of BIBF 1120, safety and pharmacokinetics in escalating doses administered with Vinorelbine i.v. in elderly patients with advanced Non-Small Lung Cancer (Stage IV).

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non Small Cell Lung Cancer - Stage IV; NSCLC Stage IV

Outcome Measures

Primary Outcomes (1)

• To investigate the maximum tolerated dose of BIBF 1120

  Cycle 1 day 1, day 2, day 8, day 15; Cycle 2 day 1, day 2, day 8, day 15; Cycle 3 day 1, day 8, day 15; Cycle 4 day 1, day 8, day 15; day 84

Secondary Outcomes (4)

• Incidence of adverse events

  Cycle 1 day 1, day 2, day 8, day 15; Cycle 2 day 1, day 2, day 8, day 15; Cycle 3 day 1, day 8, day 15; Cycle 4 day 1, day 8, day 15; day 84

• Pharmacokinetic parameters: Aerea Under Curve (AUC)

  0,15, 0,50, 1, 1,50, 2, 3, 4, 6, 7, 24, 24,15, 24,50, 25, 25,5, 26, 27, 28, 30, 31, 48, 168 hours post dose

• Pharmacokinetic parameters: C-max

  0,15, 0,50, 1, 1,50, 2, 3, 4, 6, 7, 24, 24,15, 24,50, 25, 25,5, 26, 27, 28, 30, 31, 48, 168 hours post dose

• Response Rate

  Day 43 (prior start of cycle 3), day 84

Study Arms (1)

BIBF 1120, Vinorelbine

EXPERIMENTAL

To determine the 'Maximum Tolerated Dose', dose escalation for BIBF 1120 will be conducted following the 3 + 3 design. A cohort of three patients will be treated at the starting dose level 150mg bid and observed until the end of the first cycle. Under certain conditions the dose level will be escalated to 200mg bid in a second cohort.

Drug: BIBF 1120; Drug: Vinorelbine

Interventions

BIBF 1120 DRUG

2 x 150 mg capsules, oral, daily (Start dose)

BIBF 1120, Vinorelbine

Vinorelbine DRUG

25 mg/m2 i.v. on day 1 and 8 (three-week cycle)

BIBF 1120, Vinorelbine

Eligibility Criteria

• Age: 71 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Histological confirmed Non-Small-Cell lung cancer (NSCLC)
• Tumor stage IV (UICC 7th Version)
• ECOG \<2
• Age \> 70 years
• No previous chemotherapy for stage IV NSCLC (UICC 7th Version)
• Adjuvant or neoadjuvant chemotherapy for NSCLC must be completed at least one year prior to study enrolment (from end of chemotherapy)
• Patients with prior radiation therapy may be eligible for this study if they meet the following guidelines:
• Previous radiation therapy is allowed to \<25% of the bone marrow (Cristy and Eckerman 1987), but should have been limited and must not have included whole pelvis radiation.
• Patients must have recovered from the toxic effects of the treatment prior to study enrolment (except for alopecia).
• Prior thoracic radiotherapy must be completed 30 days before study enrolment.
• Lesions that have been irradiated cannot be included as sites of measurable disease unless clear tumour progression has been documented in these lesions since the end of radiation therapy.
• Palliative extrathoracic radiotherapy to pre-existing lesions may continue on study; however, these lesions may not be included as sites of measurable disease.
• Adequate haematological laboratory parameters:
• Haemoglobin ≥9 g/dl
• WBC ≥3.000/µl

You may not qualify if:

• Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardise compliance with the protocol
• Serious infections requiring systemic antibiotic (e.g antiviral, antimicrobial, antifungal) therapy
• Investigational drug therapy outside of this trial during or within 4 weeks of study entry
• Known hypersensitivity to the trial drugs or their excipients.
• History of other malignancies in the last 5 years, in particular those which could affect compliance with the protocol or interpretation of results. Patients with adequately treated basal or squamous cell skin cancer are generally eligible.
• Serious concomitant disease, especially those that would limit compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the investigator would make the patient inappropriate for entry into the trial.
• Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 9 months, congestive heart failure \> NYHA II)
• Known inherited predisposition to bleeds or to thrombosis.
• Patient with brain metastases that are symptomatic and/or require therapy.
• Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy(except for chronic low-dose therapy with acetylsalicylic acid ≤325mg per day)
• History of major thrombotic events or clinically relevant major bleeding event in the past 6 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis below the joint space of the knee)
• Current peripheral neuropathy ≥ CTCAE grade 2 except due to trauma
• Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
• Active alcohol or drug abuse.
• Men who are sexually active and unwilling to use a medically acceptable method of contraception

Sponsors & Collaborators

• Aktion Bronchialkarzinom e.V.: lead
• Boehringer Ingelheim: collaborator

Study Sites (4)

Klinikum Kassel GmbH

Kassel, Hesse, 34125, Germany

Location

LungenClinic Großhansdorf GmbH

Großhansdorf, 22927, Germany

Location

Thoraxklinik Universitätsklinikum Heidelberg

Heidelberg, D-69126, Germany

Location

Klinikum der Universität München

München, D-80336, Germany

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

nintedanib; Vinorelbine

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)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Prof. Dr. Rudolf M. Huber, MD

  Klinikum der Universität München, D-80336 München

  PRINCIPAL INVESTIGATOR

• Prof. Dr. Martin Wolf, MD

  Klinikum Kassel GmbH, D-34125 Kassel

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2012
• First Posted: September 12, 2012
• Study Start: June 1, 2013
• Primary Completion: January 1, 2016
• Last Updated: January 18, 2016

Record last verified: 2016-01

Locations

DE (4)