Comparison of a standard chemotherapy with additional medication (Ramucirumab) in one group for patients with metastatic colorectal cancer after chemotherapie

Phase 1

• Conditions: Advanced metastatic colorectal cancer; MedDRA version: 27.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004162-99-DE
• Lead Sponsor: Frankfurter Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-04-04
• Last Update Posted: 8 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 426

Inclusion Criteria

1. Metastatic and inoperable, colorectal cancer who has progressed on/after, 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
2. Signed informed consent before start of specific protocol procedure
3. Histologically or cytologically documented diagnosis of adenocarcinoma of the colon or rectum
4. Presence of at least one measurable site of disease following RECIST 1.1 criteria
5. ECOG performance 0-1
6. Known RAS and BRAF V600E mutational status
Note: If KRAS (or NRAS) is mutated, NRAS (or KRAS, respectively) and BRAF mutational status is not required as the mutations are mutually exclusive and NRAS (or KRAS, respectively) and BRAF is assumed as wildtype then.
7. Life expectancy of at least 3 months
8. Adequate hematological, hepatic and renal function parameters:
a. Leukocytes = 3000/mm³, platelets = 100,000/mm³, neutrophil count (ANC) =1500/µL, hemoglobin =9 g/dL (5.58 mmol/L),
b. Adequate coagulation function as defined by International Normalized Ratio (INR) = 1.5, and a partial thromboplastin time (PTT) = 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin/ phenprocoumon must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy.
c. 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)
d. 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)
e. 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
9. Patient able and willing to provide written informed consent and to comply with the study protocol
10. Female and male patients = 18. Patients in reproductive age must be willing to use adequate contraception during the study and for 7 months after the end of ramucirumab treatment (Appropriate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, vasectomy) or hormonal contraception (implantable, patch, oral). Women who use a hormonal contraception method should use an additional barrier method like IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 426
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 426

Exclusion Criteria

1. Known hypersensitivity against ramucirumab or TAS102
2. Other known contraindications against ramucirumab, TAS102, or other anti-angiogenic therapies
3. Prior therapy with TAS102
4. Drug-related severe adverse events upon pretreatment with anti-angiogenic drugs that would require permanent discontinuation and not allow re-challenge with the same class of drug (i.e. Ramucirumab) such as nonctrollable severe hypertension or thromboembolic events (see Table 16 on p. 66 for additional examples).
5. Any antineoplastic treatment including irradiation within 14 days (42 days for mitomycin c) prior to start of therapy.
6. 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
7. Symptomatic brain metastasis
8. Clincially significant cardiovascular disease
- NYHA>II°, myocardial infarction within 6 months prior study entry
- Known clincially 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
9. Active clinically serious infections (> grade 2 NCI-CTC version 4.0)
10. Chronic inflammatory bowel disease
11. History of uncontrolled HIV infection or chronic hepatitis B or C
12. Patients with evidence of bleeding diathesis
13. Grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy
14. Receiving chronic antiplatelet therapy, including aspirin (Once-daily aspirin use (maximum dose 325 mg/day) is permitted), nonsteroidal anti-inflammatory drugs (including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents
15. History of gastrointestinal perforation or fistulae in past 6 months or risk factors for perforation
16. Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy
17. Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, Stage I uterine cancer or early breast cancer. Other here non-listed malignancies should be discussed with the coordinating investigatior before enrolment of the patient.
18. Any condition that could jeopardize the safety of the patient and their compliance of the study
19. Medical, psychological or social conditions that may interfere with the participation in the study
20. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or ascites. Clinically meaningful ascites is defined as ascites from cirrhosis requir

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified