Clinical Trial to investigate the efficacy and safety of nintedanib/vargatef when combined with paclitaxel (chemotherapy) for treatment of patients suffering from metastatic melanoma with BRAF wildtyp
- Conditions
- Advanced (unresectable stage III or IV) BRAF V600 wildtype cutaneous malignant melanomaMedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-004458-34-DE
- Lead Sponsor
- niversity of Essen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 126
1. Histologically confirmed, (surgically incurable or unresectable) stage III or IV, BRAF
V600 wildtype metastatic cutaneous malignant melanoma.
2. Written informed consent
3. A minimum of 1 measurable lesion according to RECIST v1.1 criteria.
4. ECOG performance status of 0-1.
5. Adequate hematologic, renal and liver function as defined by laboratory values
performed within 14 days prior to initiation of dosing:
• Hematologic:
o Absolute neutrophil count (ANC) =1.5 x 109/L
o Hemoglobin = 9 g/dL (5.6 mmol/L; Subjects may not have had a transfusion
within 7 days of screening assessment)
o Platelets: = 100 x 109/L
• Hepatic
o Total bilirubin: = 1.0 x ULN
o AST and ALT: = 1.5 x ULN (In the case of liver metastases: 2.5 x ULN)
• Renal
o Serum creatinine: = 1.5 mg/dL (133 µmol/L) or, if greater than 1.5 mg/dL:
Calculated creatinine clearance: = 50 mL/min
6. Women of childbearing potential (WOCBP) should be using an effective method of
contraception (Pearl-Index <1) to avoid pregnancy for at least 6 months after completion
of paclitaxel treatment and for at least 3 months after completion of nintedanib/placebo
monotherapy as directed by their physician. Women will be considered to be of
childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal
ligation/salpingectomy, or post-menopausal for at least two years. WOCBP must have a
negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units
of HCG) up to 28 days prior to commencement of dosing.
7. Men should use an effective method of contraception during treatment and for at least 6
months after completion of paclitaxel treatment and for at least 3 months after
completion of nintedanib/placebo monotherapy as directed by their physician.
8. Patients must have recovered from all prior treatment-related toxicities to NCI CTCAE
(v4.0) Grade of 0 or 1, except for toxicities not considered a safety risk such as alopecia.
9. Male or female, aged 18 years or older
10. Life expectancy at least 3 months
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 63
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 63
1. Prior systemic therapy with taxanes or kinase inhibitors. Any prior therapy for metastatic
disease must have been discontinued at least 4 weeks prior to initiation of dosing.
2. Major surgery or radiation therapy within 4 weeks of starting the study treatment (minor
surgical procedures such as biopsies are allowed, however patients must have
recovered).
3. Known inherited predisposition to bleeding or thrombosis and therapeutic
anticoagulation (except low-dose heparin and/or heparin flush as needed for
maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for
low-dose therapy with acetylsalicylic acid < 325mg per day)
Patients with the following coagulation parameters will be excluded:
o International normalised ratio (INR) > 2
o Prothrombin time (PT) and partial thromboplastin time (PTT): > 50% of deviation
of institutional ULN
4. History of clinically significant haemorrhagic or thromboembolic event in the past 6
months
5. NCI CTCAE (V4.0) grade 3 hemorrhage within 4 weeks of starting the study treatment.
6. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within 6 months prior to randomization.
7. Serious, non-healing wound, ulcer, or bone fracture.
8. Known CNS disease.
9. Previous Grade 2 or higher sensory neuropathy.
10. History of or known spinal cord compression, or carcinomatous meningitis, or evidence
of active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment
with radiotherapy, symptomatic, requiring treatment with anti-convulsants;
dexamethasone therapy will be allowed if administered as stable dose for at least one
month before randomization) or leptomeningeal disease on screening CT or MRI scan.
11. Any of the following within the 6 months prior to enrolment: myocardial infarction,
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic
congestive heart failure, cerebrovascular accident or transient ischemic attack, or
pulmonary embolism.
12. New York Heart Association (NYHA) Grade II or greater congestive heart failure.
13. Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade = 2.
14. Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications).
15. Symptomatic peripheral vascular disease.
16. Proteinuria at screening as demonstrated by urine dipstick for proteinuria = 2+ (patients
discovered to have = 2+ proteinuria on dipstick urinalysis at baseline should undergo a
24 hour urine collection and must demonstrate = 1g of protein in 24 hours to be eligible).
17. Known hypersensitivity reaction to any of the components of study treatment (e.g.
contrast media) or other severe acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method