A Study to test the combination of two new drugs for nine rare cancer types.
- Conditions
- Mutations of BRAF V600E have been identified at a high frequency in melanoma, PTC, colorectal and ovarian cancers. Such mutations have also been reported in some rare cancers such as anaplastic thyroid cancer, hairy cell leukemia, gastrointestinal stromal tumors, non-seminomatous/non-geminomatous germ cell tumors, biliary tract cancer, multiple myeloma, adenocarcinoma of the small intestine, World Health Organization Grade 1 and 2 gliomas and WHO Grade 3 and 4 gliomas.MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-001705-87-AT
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 135
1. Signed, written informed consent
2. Sex: male or female
3. Age: > or = to 18 years of age at the time of providing informed consent
4. Eastern Cooperative Oncology Group (ECOG) performance status: 0, 1 or 2
(Appendix 1).
5. Must have advanced disease and no standard treatment options as determined by locally/regionally available standards of care and treating physician’s discretion.
6. Must have a BRAF V600E mutation-positive tumor as confirmed by an approved local laboratory or a sponsor designated central reference laboratory.
NOTE: All subjects must provide an archived or fresh tumor sample (for solid tumors) or a fresh BM aspirate and peripheral blood sample (for HCL and MM) for confirmation testing of the BRAF V600E mutation by a sponsor designated central reference laboratory using a sponsor designated assay
7. ATC, BTC, GIST, NSGCT/NGGCT, and ASI ONLY: Must have at least one
measurable lesion per RECIST 1.1 outside of a prior radiation field or within the field with evidence of progression.
8. Able to swallow and retain orally administered medication.
9. Female Subjects of Childbearing Potential: Subjects must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment and agrees to use highly effective contraception, as defined in Section 9.1, from 7 days prior to enrollment, throughout the treatment period and for 16 weeks following discontinuation of trametinib when taken in combination with dabrafenib, or for 2 weeks following discontinuation of dabrafenib monotherapy
10. Has adequate baseline organ function as outlined in Table 3: Updates legend 2 as follows: PTT and PT/INR >1.5 times ULN will be
acceptable in case of subjects receiving therapeutic anticoagulants such as warfarin as long as INR is monitored during the study according to clinical practice.
11. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
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 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
Please reference to Section 5.2.2.1 for Histology Specific Exclusion Criteria.
1. Prior treatment with:
•BRAF and/or MEK inhibitor(s)
• Chemotherapy, immunotherapy, biologic therapy or chemoradiation with delayed toxicity within 21 days (or within 42 days if prior therapy contains nitrosourea or mitomycin C) prior to enrolment
• Chemotherapy or biologic therapy without evidence of delayed toxicity
•Investigational product(s) IP within 30 days or 5 half-lives, whichever is longer, prior to enrolment
- Subjects enrolled in France: Subject has participated in any study using an investigational product (IP) within 30 days prior to enrollment in this study.
2. History of malignancy with confirmed activating RAS mutation at any time.
3. Prior radiotherapy less than 14 days prior to enrolment, except for WHO Grade 1-4 glioma and ATC. Treatment-related
AE´s must have resolved prior to enrollment
For WHO Grades 1, 2, 3, or 4 Glioma ONLY: Radiotherapy is not permitted
within 3 months prior to enrollment (extended period of time of >3 months
needed to prevent subjects with pseudo-progression from radiotherapy from being enrolled in the study). Subjects may be =2 weeks from radiotherapy if a new lesion relative to the pre-radiation MRI develops outside the primary radiation field. Treatment-related AEs must have resolved prior to enrolment.
For ATC Only: Radiotherapy is not permitted within 7 days prior to enrollment.
Treatment-related toxicity must have resolved prior to enrollment.
4.Prior major surgery less than 14 days prior to enrolment. Any surgery-related AE(s) must have resolved prior to enrolment.
5. Prior solid organ transplantation or allogenic stem cell transplantation (ASCT)
6. History of another malignancy
7. Presence of:
•Brain metastases (except for subjects in the WHO Grade 1 or 2 Glioma or
WHO Grade 3 or 4 Glioma histology cohorts) that are symptomatic or
untreated or not stable for =3 months (must be documented by imaging) or
requiring corticosteroids. Subjects on a stable dose of corticosteroids >14 days and have not required treatment with enzyme-inducing anticonvulsants for >30 days prior to enrollment can be enrolled with
approval of the Medical Monitor.
•symptomatic or untreated leptomeningeal or spinal cord compression
•Interstitial lung disease or pneumonitis
•Any unresolved =Grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) toxicity from previous anti-cancer therapy at the time of enrollment, except alopecia or Grade 2 anemia
NOTE: Subjects with MM who have =Grade 2 peripheral neuropathy (per CTCAE v4.0) are permitted.
•Any serious and/or unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with subject’s safety. obtaining informed consent or compliance to the study procedures
8. History of retinal vein occlusion (RVO)
9. Clinically significant GI abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. For example, subjects should have no more than 50% of the large intestine removed and no sign of malabsorption (i.e., diarrhea).
10. History or evidence of cardiovascular risk including any of the following:
•Acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment
•Clinically significant uncontrolled arrhythmias
•Class II or higher congestive heart failure
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