RAMucirumab in Combination Wth TAS102 vs. TAS102 Alone in Chemotherapy Refractory Metastatic Colorectal Cancer Patients

NCT03520946 | Completed Phase 3 DMC

• 2 other identifiers: RAMTAS2017-004162-99
• Study Type: interventional
• Target: 430
• Locations: 1 country
• Sites: 28

Brief Summary

Interventional, prospective, randomized (1:1), controlled, open label, multicenter phase IIb study in patients with advanced metastatic colorectal cancer. The scope of the trial is to evaluate overall survival of either regimen (TAS102 +/- Ramucirumab) and evaluate safety and tolerability.

Conditions

Colorectal Cancer

Keywords

colorectal cancer; ramucirumab; tas102

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Overall survival according to Kaplan-Meier

  Up to 4 years

Secondary Outcomes (9)

• Overall response rate (ORR)

  Up to 4 years

• Disease control rate (DCR)

  Up to 4 years

• Progression-free survival (PFS)

  Up to 4 years

• Overall survival (OS) rate at different time points

  6 months and 1 year

• Efficacy (ORR) subgroup

  Up to 4 years

Other Outcomes (3)

• Explorative: Overall response rate (ORR)

  Up to 4 years

• Explorative: Overall survival (OS)

  Up to 4 years

• Explorative: Progression-free survival (PFS)

  Up to 4 years

Study Arms (2)

Arm A (ramucirumab + TAS102)

EXPERIMENTAL

Patients randomized to arm A will receive ramucirumab 8 mg/kg iv over 60 min on d1+15, q4w and TAS102 35mg/m2 p.o. twice daily (BID) d1-5 and 8-12, q4w until progression or intolerance or completion of 6 cycles.

Drug: Ramucirumab; Drug: TAS 102

Arm B (TAS102 only)

ACTIVE COMPARATOR

Patients randomized to arm B will receive TAS102 35mg/m2 p.o. twice daily (BID) d1-5 and 8-12, q4w until progression, intolerance or completion of 6 cycles.

Drug: TAS 102

Interventions

Ramucirumab DRUG

8 mg/kg iv over 60 min on d1+15, q4w

Arm A (ramucirumab + TAS102)

TAS 102 DRUG

35mg/m2 p.o. twice daily (BID) d1-5 and d8-12, q4w

Arm A (ramucirumab + TAS102); Arm B (TAS102 only)

Eligibility Criteria

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

You may qualify if:

• Metastatic and inoperable, colorectal cancer who has progressed on/after, or did not tolerate, refuse or have contraindications to: fluoropyrimidines, oxaliplatin, irinotecan, anti-angiogenic therapies (bevacizumab, aflibercept, regorafenib or ramucirumab) and if indicated anti-EGFR antibodies (cetuximab or panitumumab).
• Intolerance is defined as a permanent discontinuation of the respective treatment resulting from toxicity
• Signed informed consent before start of specific protocol procedure
• Histologically or cytologically documented diagnosis of adenocarcinoma of the colon or rectum
• Presence of at least one measurable site of disease following RECIST 1.1 criteria
• ECOG (Eastern Cooperative Oncology Group) performance 0-1
• Known RAS and BRAF V600E mutational status
• Life expectancy of at least 3 months
• Adequate hematological, hepatic and renal function parameters:
• Leukocytes ≥3000/mm³, platelets ≥100,000/mm³, neutrophil count (ANC) ≥1500/μL, hemoglobin ≥9 g/dL (5.58 mmol/L)
• Adequate coagulation function as defined by International Normalized Ratio (INR) ≤1.5, and a partial thromboplastin time (PTT) ≤5 seconds above the ULN (upper limit of normal) (unless receiving anticoagulation therapy). Patients receiving warfarin/phenprocoumon must be switched to low molecular weight heparin and have achieved a stable coagulation profile prior to first dose of protocol therapy
• Serum creatinine ≤1.5 x upper limit of normal or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is \>1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed)
• Urinary protein ≤1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥2+, a 24-hour urine collection for protein must demonstrate \<1000 mg of protein in 24 hours to allow participation in this protocol)
• Bilirubin ≤1.5 x upper limit of normal, AST and ALT ≤3.0 x upper limit of normal, ≤5xULN if liver metastasis present, alkaline phosphatase ≤6 x upper limit of normal
• Patient able and willing to provide written informed consent and to comply with the study protocol

You may not qualify if:

• Known hypersensitivity against ramucirumab or TAS102
• Other known contraindications against ramucirumab, TAS102, or other anti-angiogenic therapies
• Prior therapy with TAS102
• Drug-related severe adverse events upon pretreatment with antiangiogenic drugs that would require permanent discontinuation and not allow re-challenge with the same class of drug (i.e. ramucirumab) such as noncontrollable severe hypertension or thromboembolic events
• Any antineoplastic treatment including irradiation within 14 days (42 days for mitomycin c) prior to start of therapy.
• Major surgery within 4 weeks of starting therapy within this study, or minor surgery/subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial.
• Symptomatic brain metastasis
• Clinically significant cardiovascular disease
• NYHA\>II°, myocardial infarction within 6 months prior study entry
• Known clinically significant valvular defect
• Uncontrolled or poorly-controlled hypertension (\>160 mmHg systolic or \>100 mmHg diastolic for \>4 weeks) despite standard medical management
• Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy
• History of deep vein thrombosis (DVT), symptomatic pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy
• Active clinically serious infections (\> grade 2 NCI-CTC version 4.0)
• Chronic inflammatory bowel disease

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Eli Lilly and Company: collaborator
• Trium Analysis Online GmbH: collaborator

Study Sites (28)

MVZ Gesundheitszentrum St. Marien GmbH

Amberg, 922241, Germany

Location

HELIOS Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Charité - Universitätsmedizin Berlin Campus Mitte

Berlin, 10115, Germany

Location

MVZ Seestrasse

Berlin, 13347, Germany

Location

St.-Johannes-Hospital

Dortmund, 44137, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Krankenhaus Nordwest GmbH

Frankfurt, 60488, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Asklepios Klinik Hamburg Barmbek

Hamburg, 22307, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Marien Hospital Herne

Herne, 44625, Germany

Location

Vincentius-Diakonissen-Kliniken gAG

Karlsruhe, 76137, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum Ludwigsburg

Ludwigsburg, 71640, Germany

Location

Tagestherapiezentrum am ITM Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

Johannes Wesling Klinikum Minden

Minden, 32429, Germany

Location

Kliniken Maria Hilf GmbH

Mönchengladbach, 41063, Germany

Location

Klinikum der Universität München-Großhadern

München, 81377, Germany

Location

Unversitätsklinikum Münster

Münster, 48149, Germany

Location

Klinikum Nürnberg

Nuremberg, 90419, Germany

Location

Studienzentrum Onkologie Ravensburg

Ravensburg, 88212, Germany

Location

MedCenter Nordsachsen

Schkeuditz, 04435, Germany

Location

Leopoldina Krankenhaus

Schweinfurt, 97422, Germany

Location

MVZ Klinik Dr. Hancken GmbH

Stade, 21680, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Klinikum Wilhelmshaven

Wilhelmshaven, 26389, Germany

Location

Hämatologisch-Onkologische Praxis

Würselen, 52146, Germany

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Ramucirumab; trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2018
• First Posted: May 11, 2018
• Study Start: January 24, 2019
• Primary Completion: July 30, 2024
• Study Completion: July 30, 2024
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (28)