A Study to Test Trametinib and dabrafenib in Children and Adolescents Subjects with Cancer
- Conditions
- Children and Adolescents with Cancers Harboring V600 mutationsMedDRA version: 20.0Level: PTClassification code 10029260Term: NeuroblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003596-35-GB
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 145
1. Written informed consent – a signed informed consent and/or assent (as age appropriate) for study participation including pharmacokinetics sampling will be obtained according to institutional guidelines;
2. Male or female between one month and < 18 years of age (inclusive) at the time of signing the informed consent form
3. Part C and Part D subjects between 12 months and < 18 years of age, inclusive
4. Part A subjects < 2 years of age will not be included in the initial dose escalation
5. Must have a disease that is relapsed/refractory to all potentially curative standard treatment regimens or must have a current disease for which there is no known curative therapy, or therapy proven to prolong survival with an acceptable quality of life.
6. Prior therapy: The subject’s disease (i.e. cancer, NF-1 with PN, or LCH) must have relapsed after or failed to respond to frontline curative therapy or there must not be other potentially curative treatment options available. Curative therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities. Subjects must have recovered to grade =1 from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment.
7. Performance score of =50% according to the Karnofsky / Lansky performance status scale.
8. Females of child-bearing potential must be willing to practice acceptable methods of birth control. Additionally, females of childbearing potential must have a negative serum pregnancy test within 7 days prior to start of study drugs;
9. In France, subjects will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
10.10. Must have adequate multi organ function as defined by the following
values: renal function - 24 hr creatinine clearance (revised Schwartz
formula), or radioisotope glomerular filtration rate (GFR) >=60 milliliter
(mL) per minute per 1.73 meter square (mL/min/1.73m^2); or a serum
creatinine <=upper limit of normal (ULN) for age and gender; liver
functions as bilirubin (sum of conjugated + unconjugated) <=1.5 x ULN
for age, alanine aminotransferase (ALT) <=2.5 x ULN; for the purposes
of enrollment and toxicity monitoring the ULN for ALT will be 45 unit per
liter (U/L); cardiac function - corrected QT (QTcB) interval <480
milliseconds (msec), left ventricular ejection fraction (LVEF) >=lower
limit of normal (LLN) by ECHO.
•Able to swallow and retain enterally (per oral [PO] or nasogastric or
gastric tube) administered medication and does not have any clinically
significant gastrointestinal abnormalities that may alter absorption such
as malabsorption syndrome or major resection of the stomach or bowels.
•Adequate Blood Pressure Control defined as: Blood pressure <= the
95th percentile for age, height, and gender.
Other protocol-defined inclusion criteria, including some for each part,
may apply
Are the trial subjects under 18? yes
Number of subjects for this age range: 145
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Lactating or pregnant female.
2. History of another malignancy including resected non-melanomatous skin cancer
3. Subjects with Neurofibromatosis Type-1 (NF-1) associated optic pathway tumors are excluded if they are actively receiving therapy for the optic pathway tumor or do not meet criteria for Plexiform Neurofibroma or malignant solid tumor
4. Subjects with a history of NF-1 related cerebral vascular anomaly (such as Moyamoya)
5. Subjects with NF-1 actively receiving therapy for the optic pathway tumour
6. Subjects with NF-1 and only Plexiform Neurofibroma (PN) lesions that cannot be evaluated by volumetric analysis
7. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures
8. Any prohibited medication(s) as described in Section 9.2.
9. Any medications for treatment of left ventricular systolic dysfunction
10. Part B cohorts 1, 2 and 3: Previous treatment with dabrafenib, trametinib or another MEK inhibitor (exception: prior treatment with sorafenib is permitted).
Patients who have had prior dabrafenib therapy may enroll into cohort B4.
Patients who have had prior dabrafenib therapy and had benefit from that therapy as determined by the investigator, are allowed in Part C or Part D
11. Administration of an investigational study treatment within 30 days preceding the first dose of study treatment(s) in this study
12. Have a known hypersensitivity reaction or idiosyncrasy to drugs chemically related to study treatment or excipients that contraindicate their participation
13. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or liver metastases)
14. History of hepatic sinusoid obstructive syndrome (Venoocculsive disease) within the prior 3 months
15. History of heparin-induced thrombocytopenia
16. History of interstitial lung disease or pneumonitis
17. History or current evidence of retinal vein occlusion (RVO)
18. For subjects with solid tumors that are not primary central nervous system (CNS) tumors or NF-1 associated plexiform neurofibromas, subjects with symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression are excluded
19. A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection
20. Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events Grade 2 or higher from previous anti-cancer therapy, except alopecia
21. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. If clarification is needed as to whether a condition will significantly affect absorption of drugs, contact the Medical Lead for guidance to enrol the subject
22. A history or evidence of cardiovascular risk including: a QT interval
corrected for heart rate using the Bazett's formula (QTcB) >=480 msec;
a history or evidence of current clinically significant uncontrolled
arrhythmias (clarification: Subjects with atrial fibrillation controlled for
>30 days prior to dosing are eligible); a history of acute coronary
syndromes (including myocardial infarction or unstable angina),
coronary angioplasty, or stenting within 6 months prior to
randomization; a history or evidence of current >=Class II cong
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