TRICC-C (AIO-KRK-0111): BIBF 1120 Versus Placebo in Patients Receiving Oxaliplatin Plus Fluorouracil and Leucovorin (mFOLFOX6) for Advanced, Chemorefractory Metastatic Colorectal Cancer (mCRC)

Colorectal Cancer Clinical Trial

— AIO-KRK-0111  

Official title:

TRICC-C: A Multicenter, Randomized, Phase II Trial: BIBF 1120 vs. Placebo in Patients Receiving Oxaliplatin Plus Fluorouracil and Leucovorin (mFOLFOX6) for Advanced, Chemorefractory Metastatic Colorectal Cancer (mCRC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01362361
• Other study ID #: TRICC-C (AIO-KRK-0111)
• Secondary ID: 2010-023050-37
• Status: Completed
• Phase: Phase 2
• Start date: June 2011
• Est. completion date: December 2016

Study information

• Verified date: September 2019
• Source: Martin-Luther-Universität Halle-Wittenberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study:

To explore the comparative effectiveness of BIBF 1120 in terms of :

• Progression-free survival (PFS), objective response, overall survival

• Evaluate and compare safety

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: December 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically proven colorectal adenocarcinoma

2. Intended treatment with mFOLFOX6 after one prior palliative chemotherapy for metastatic CRC

3. Age > 18 years

4. Metastatic disease not suitable for curative-intent surgery

5. Measurable (> 1 cm) and evaluable disease (according to RECIST 1.1 criteria)

6. Prior bevacizumab, cetuximab or panitumumab are allowed.

7. Previous adjuvant oxaliplatin-containing therapy is allowed, if the end of adjuvant chemotherapy is >12 months prior to inclusion into the trial

8. ECOG performance status 0 or 1 (see appendix 10.4)

9. Adequate hepatic function

10. Adequate Renal function

11. Adequate bone marrow function

12. Other lab parameters: proteinuria < CTCAE grade 2, Prothrombin time and/or partial thromboplastin time < 50 % deviation from normal limits

13. Life expectancy at least 3 months

14. Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation

Exclusion Criteria:

1. Known hypersensitivity to the trial drugs or their excipients.

2. Treatment with any investigational drug within 28 days of trial onset.

3. Prior treatment with more than one line of palliative standard chemotherapy for colorectal cancer, prior treatment with a tyrosine kinase inhibitor, prior palliative treatment with an oxaliplatin-containing regime.

4. 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.

5. 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.

6. Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion, or planned surgical procedures during the trial period. Portimplantation prior to therapy is allowed.

7. Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 9 months, congestive heart failure > NYHA II) (see appendix 10.3).

8. History of severe haemorrhagic or thrombotic events in the past 12 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis). Known inherited predisposition to bleeds or to thrombosis.

9. Patient with brain metastases that are symptomatic and/or require therapy.

10. 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)

11. History of major thrombotic or clinically relevant major bleeding event in the past 6 months

12. Current peripheral neuropathy = CTCAE grade 2 except due to trauma

13. Serious infections requiring systemic antibiotic (e.g antiviral, antimicrobial, antifungal) therapy

14. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug

15. Active alcohol or drug abuse.

16. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception

17. Pregnancy or breast-feeding

18. Leptomeningeal disease

19. Radiographic evidence of cavitary or necrotic tumours

20. Centrally located tumours with radiographic evidence (CT or MRI) of local invasion of major blood vessels

21. Severe chemotherapy-associated toxicity during or after adjuvant or palliative first-line chemotherapy like 5-FU-associated cardiac toxicity (coronary spasm) or persistent oxaliplatin-associated peripheral neuropathy (= CTCAE grade 2) with paresthesia associated with pain or functional impairment (after adjuvant oxaliplatin-containing chemotherapy).

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• mFOLFOX6 + BIBF 1120
mFOLFOX6 + BIBF1120 (2x200 mg/d d1-d14) (repeated every 14 days)
• mFOLFOX6+placebo
mFOLFOX6 + placebo (2x200 mg/d d1-d14) (repeated every 14 days)

Locations

Country	Name	City	State
Germany	Schwerpunktpraxis für Hämatologie und Onkologie Bottrop und Dorsten	Bottrop
Germany	Universitätsklinikum Greifswald -Klinik für Innere Medizin A	Greifswald
Germany	Gemeinschaftspraxis und Tagesklinik Onkologie und Gastroenterologie - Halle	Halle
Germany	Universitätsklinikum Halle	Halle	Sachsen-Anhalt
Germany	Klinikum Karlsruhe, Medizinische Klinik III	Karlsruhe
Germany	Kliniken der Stadt Köln gGmbH - Krankenhaus Holweide	Köln
Germany	Universitätsmedizin Mannheim - TTZ am Interdisziplinären Tumorzentrum	Mannheim
Germany	Joh. Wesling Klinikum Minden	Minden
Germany	Klinikum der Universität München-Großhadern - Medizinische Klinik und Poliklink III	München
Germany	Stauferklinikum Schwäbisch Gmünd - Mutlangen - Zentrum Innere Medizin	Mutlangen
Germany	Leopoldina-Krankenhaus Schweinfurt - Medizinische Klinik 2	Schweinfurt
Germany	Universitätsklinikum Ulm - Klinik für Innere Medizin I	Ulm

Sponsors (2)

Lead Sponsor	Collaborator
Martin-Luther-Universität Halle-Wittenberg	GALMED GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression free survival		1 year