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CancerPhase 2NCT02034110

Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib in Subjects With BRAF V600E- Mutated Rare Cancers

A Phase 2 study testing Dabrafenib and Trametinib in people with Cancer, run by Novartis Pharmaceuticals at 41 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This was a Phase II, open-label, non-randomized, multi-center study of oral dabrafenib in combination with oral trametinib in subjects with rare cancers harboring the BRAF V600E mutation including anaplastic thyroid cancer (ATC), biliary tract cancer (BTC), gastrointestinal stromal tumor (GIST), low grade (WHO G1/G2)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer
What is being tested?
Dabrafenib and Trametinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
206 participants
Where
41 sitesin 14 countries
Study dates
12 Mar 2014to 10 Dec 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed, written informed consent.
  • Sex: male or female.
  • Age: >=18 years of age at the time of providing informed consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0, 1 or 2.
  • Must have advanced disease and no standard treatment options as determined by locally/regionally available standards of care and treating physician's discretion
  • Must have a a BRAF V600E mutation-positive tumor as confirmed by an approved local laboratory or a sponsor designated central reference laboratory. 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
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  • Able to swallow and retain orally administered medication. NOTE: Subject should not have any clinically significant gastrointestinal (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).NOTE: If clarification is needed as to whether a condition will significantly affect the absorption of study treatments, contact the GSK Medical Monitor.
  • 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 effective contraception, throughout the treatment period and for 4 months after the last dose of study treatment.
  • 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

Who cannot join

  • Prior treatment with: BRAF and/or MEK inhibitor(s); anti-cancer therapy (e.g., chemotherapy with delayed toxicity, immunotherapy, biologic therapy or chemoradiation) within 21 days or prior nitrosourea or mitomycin C containing therapy within 42 days prior to enrollment and/or prior daily or weekly chemotherapy or biologic therapy without the potential for delayed toxicity within 14 days prior to enrolment or prior nvestigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to enrollment
  • History of malignancy with confirmed activating RAS mutation at any time. Prospective RAS testing is not required. However, if the results of previous RAS testing are known, then those results must be used in assessing eligibility.
  • Prior radiotherapy less than 14 days prior to enrollment, except for WHO Grade 1 4 glioma (radiotherapy is not permitted within 3 months prior to enrollment) and ATC (radiotherapy is not permitted within 7 days prior to enrollment). Treatment-related AEs must have resolved prior to enrollment.
  • Prior major surgery less than 14 days prior to enrollment. Any surgery-related AE(s) must have resolved prior to enrollment
  • Prior solid organ transplantation or allogenic stem cell transplantation (ASCT). However, previous autologous BM transplant (ABMT) or autologous peripheral blood stem cell transplant (PBSCT) is permitted.
  • History of another malignancy. Subjects with another malignancy are eligible if: (a) disease-free for 3 years, or (b) have a history of completely resected non-melanoma skin cancer, and/or (c) have an indolent second malignancy(ies).
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  • Presence of brain metastases (except for subjects in the WHO Grade 1 or 2 or 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
  • Presence of symptomatic or untreated leptomeningeal or spinal cord compression. Subjects who have been previously treated for these conditions and have stable CNS disease (documented by consecutive imaging studies) for >60 days, are asymptomatic and currently not taking corticosteroids, or have been on a stable dose of corticosteroids for at least 30 days prior to enrollment, are permitted
  • Presence of interstitial lung disease or pneumonitis
  • Presence of 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. Subjects with MM who have ≤Grade 2 peripheral neuropathy (per CTCAE v4.0) are permitted.
  • Presence of 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
  • History of retinal vein occlusion
  • 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)
  • 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 enrolment; clinically significant uncontrolled arrhythmias; however, subjects with controlled atrial fibrillation for >30 days prior to enrollment are eligible; class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) criteria; left ventricular ejection fraction (LVEF) below the institutional LLN. If a LLN does not exist at an institution, then use LVEF <50%; abnormal cardiac valve morphology (≥Grade 2) documented by ECHO; however, subjects with Grade 1 abnormalities (i.e., mild regurgitation/stenosis) may be entered on study but subjects with moderate valvular thickening should NOT be enrolled; corrected QT (QTc) interval for heart rate using Bazett-corrected QT interval (QTcB) >=480 msec; intracardiac defibrillator; treatment-refractory hypertension defined as a blood pressure (BP) >140/90 mmHg which may not be controlled by anti-hypertensive medication(s) and/or lifestyle modifications
  • Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result within 3 months prior to first dose of study treatment. Subjects with positive Hepatitis C antibody due to prior exposure can be enrolled, only if a confirmatory negative Hepatitis C RNA polymerase chain reaction (PCR) test is obtained.
  • Current use of prohibited medication(s) or requirement for prohibited medications during study as per the study protocol. Use of anticoagulants such as warfarin is permitted; however, international normalization ratio (INR) must be monitored according to local institutional practice.
  • Clinically significant known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study treatment, or excipients, or to dimethyl sulfoxide (structural component of dabrafenib).
  • Pregnant, lactating or actively breastfeeding female subjects

Trial locations and contacts

41 sites in 14 countries.

41 sites in 14 countries

United States8 sites

  • Novartis Investigative Site

    Bethesda, Maryland, 20892

  • Novartis Investigative Site

    Boston, Massachusetts, 02114

  • Novartis Investigative Site

    Boston, Massachusetts, 02215

  • Novartis Investigative Site

    Houston, Texas, 77030

  • Novartis Investigative Site

    Little Rock, Arkansas, 72205

  • Novartis Investigative Site

    Nashville, Tennessee, 37203

  • Novartis Investigative Site

    New York, New York, 10016

  • Novartis Investigative Site

    Santa Monica, California, 90404

Other trials in United States

France6 sites

  • Novartis Investigative Site

    Bordeaux, 33076

  • Novartis Investigative Site

    Lyon, 69373

  • Novartis Investigative Site

    Nantes, 44093

  • Novartis Investigative Site

    Saint-Herblain, 44805

  • Novartis Investigative Site

    Toulouse, 31059

  • Novartis Investigative Site

    Villejuif, 94805

Other trials in France

Germany5 sites

  • Novartis Investigative Site

    Berlin, 13353

  • Novartis Investigative Site

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • Novartis Investigative Site

    Hamburg, 20246

  • Novartis Investigative Site

    Heidelberg, Baden-Wurttemberg, 69120

  • Novartis Investigative Site

    Mannheim, Baden-Wurttemberg, 68167

Other trials in Germany

Austria4 sites

  • Novartis Investigative Site

    Innsbruck, 6020

  • Novartis Investigative Site

    Linz, 4020

  • Novartis Investigative Site

    Salzburg, 5020

  • Novartis Investigative Site

    Vienna, 1090

Other trials in Austria

Netherlands4 sites

  • Novartis Investigative Site

    Amsterdam, 1066 CX

  • Novartis Investigative Site

    Amsterdam, 1081 HV

  • Novartis Investigative Site

    Rotterdam, 3015 GD

  • Novartis Investigative Site

    Utrecht, 3584 CX

Other trials in Netherlands

Italy3 sites

  • Novartis Investigative Site

    Milan, Lombardy, 20132

  • Novartis Investigative Site

    Milan, Lombardy, 20133

  • Novartis Investigative Site

    Milan, Lombardy, 20141

Other trials in Italy

Japan2 sites

  • Novartis Investigative Site

    Chiba, 277-8577

  • Novartis Investigative Site

    Tokyo, 104-0045

Other trials in Japan

South Korea2 sites

  • Novartis Investigative Site

    Seoul, 03080

  • Novartis Investigative Site

    Seoul, 06273

Other trials in South Korea

Spain2 sites

  • Novartis Investigative Site

    Barcelona, 08035

  • Novartis Investigative Site

    Madrid, 28041

Other trials in Spain

Belgium1 site

  • Novartis Investigative Site

    Jette, 1090

Other trials in Belgium

Canada1 site

  • Novartis Investigative Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Denmark1 site

  • Novartis Investigative Site

    Copenhagen, 2100

Other trials in Denmark

Norway1 site

  • Novartis Investigative Site

    Oslo, 0310

Other trials in Norway

Sweden1 site

  • Novartis Investigative Site

    Stockholm, 171 76

Other trials in Sweden

About this study

Official title: A Phase II, Open-label, Study in Subjects With BRAF V600E-Mutated Rare Cancers With Several Histologies to Investigate the Clinical Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib

This was a Phase II, open-label, non-randomized, multi-center study of oral dabrafenib in combination with oral trametinib in subjects with rare cancers harboring the BRAF V600E mutation including anaplastic thyroid cancer (ATC), biliary tract cancer (BTC), gastrointestinal stromal tumor (GIST), low grade (WHO G1/G2) glioma (LGG), high grade (WHO G3/G4) glioma (HGG), non-seminomatous germ cell tumors (NSGCT) / non-germinomatous germ cell tumors (NGGCT), adenocarcinoma of the small intestine (ASI), hairy cell leukemia (HCL) and multiple myeloma (MM).

Read the detailed description

This study was designed to determine the overall response rate (ORR) of oral Dabrafenib in combination with oral Trametinib in subjects with rare BRAF V600E mutated cancers. Subjects needed to have a fresh or frozen tumor tissue sample provided to confirm the BRAF V600E mutation status. Only subjects with histologically confirmed advanced disease and no available standard treatment options were eligible for enrollment. Subjects underwent screening assessments within 14 days (up to 35 days for ophthalmology exam, echocardiogram or disease assessments) prior to the start of treatment to determine their eligibility for enrollment in the study. All subjects enrolled received oral dabrafenib 150 mg bid in combination with oral trametinib 2 mg once daily. Subjects continued treatment until an unacceptable toxicity, disease progression, withdrawal of consent or death. Once a subject discontinued treatment, a post-treatment follow-up visit was conducted within 28 days (+ 7 days) after the last dose of study treatment(s). Extended follow-up visits were conducted every 4 weeks (+/- 7 days) for the first 6 months and then every 3 months (+/- 14 days) thereafter. A subject was considered to have discontinued the study if the subject was lost to follow-up or withdrew consent or another reason existed that prevented additional data from being collected on the subject. A subject was considered to have completed the study at the time of death.

For each histology, up to 25 patients were planned to be enrolled in each of the 9 primary analysis cohorts. A cohort could be closed or stopped early (prior to capping at 25 patients) for futility or efficacy. An uncapped expansion cohort was planned when a particular cohort was stopped early for efficacy. All planned histology cohorts enrolled at least one subject, with the exception of the germ cell tumor cohort. Enrolment in the study was closed in July 2018.

Conditions
Cancer
Being tested
Dabrafenib, Trametinib
Keywords
solid tumors, anaplastic thyroid cancer (ATC), biliary tract cancer (BTC), gastrointestinal stromal tumor (GIST), low grade (WHO G1/G2) glioma (LGG), high grade (WHO G3/G4) glioma (HGG), non-seminomatous germ cell tumors (NSGCT)/non-germinomatous germ cell tumors (NGGCT), adenocarcinoma of the small intestine (ASI), hairy cell leukemia (HCL), multiple myeloma (MM), efficacy, safety, BRAF V600E mutation, Trametinib, Dabrafenib
Medical subject headings
Neoplasms, Thyroid Carcinoma, Anaplastic, Biliary Tract Neoplasms, Gastrointestinal Stromal Tumors, Glioma, Nonseminomatous germ cell tumor, Leukemia, Hairy Cell, Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DabrafenibDrug

    Also called DRB436, GSK2118436

    A 150 mg twice daily capsule administered orally on a continuous basis.

  • TrametinibDrug

    Also called TMT212, GSK1120212

    A 2 mg once daily tablet administered orally on a continuous basis.

Study groups in NCT02034110
Study groupRoleWhat they receive
Dabrafenib + TrametinibExperimentalSubjects received Dabrafenib 150 mg twice daily orally plus Trametinib 2 mg once daily orally on a continuous basis. Dabrafenib was administered under fasted conditions, either 1 hour (hr) before or 2 hours (hrs) after a meal with approximately 200 mL of water with an interval of 12 hours. Trametinib was administered under fasted conditions, either 1 hr before or 2 hrs after a meal with approximately 200 mL of water. Subjects took their dose of Trametinib concurrently with the morning dose of Dabrafenib. A treatment cycle was 28 days in duration. Subjects continued treatment until an unacceptable toxicity, disease progression, or death occurs.
Receives: Drug: Dabrafenib; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR) in the Anaplastic Thyroid Cancer (ATC) Cohort

    Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response [CR], partial response [PR]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)

  2. Overall Response Rate (ORR) in the Biliary Tract Cancer (BTC) Cohort

    Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response [CR], partial response [PR]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)

  3. Overall Response Rate (ORR) in the Gastrointestinal Stromal Tumor (GIST) Cohort

    Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response [CR], partial response [PR]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)

  4. Overall Response Rate (ORR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort

    Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (complete response [CR], partial response [PR]) by investigator assessment as defined by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)

  5. Overall Response Rate (ORR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort

    Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (response assessment criteria (CR, PR, and minor response [MR]) WHO Grade 1 and 2 Glioma) by investigator assessment as defined by response assessment for neuro-oncology (RANO). Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.

    Measured: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)

  6. Overall Response Rate (ORR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort

    Overall Response Rate (ORR) was defined as the percentage of participants with a tumor response (updated response assessment criteria (CR, PR) WHO Grade 3 and 4 Glioma) by investigator assessment as defined by modified response assessment for neuro-oncology (RANO). Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.

    Measured: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)

  7. Overall Response Rate (ORR) in the Hairy Cell Leukemia (HCL) Cohort

    Overall Response Rate (ORR) was defined as the percentage of participants with CR +/- minimal residual disease [MRD], PR by investigator assessment as defined by the Consensus Resolution Criteria adapted from the National Comprehensive Cancer Network (NCCN) guidelines. Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.

    Measured: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)

  8. Overall Response Rate (ORR) in the Multiple Myeloma (MM) Cohort

    Overall Response Rate (ORR) was defined as the percentage of participants with stringent complete response (sCR), CR, PR, very good partial response (VGPR) by investigator assessment as defined by the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. Specifically, ORR = number of subjects with a confirmed overall response divided by the total number of subjects in the corresponding analysis population.

    Measured: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)

Secondary outcomes (22)

  1. Duration of Response (DoR) in the Anaplastic Thyroid Cancer (ATC) Cohort

    For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.

    Measured: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  2. Duration of Response (DoR) in the Biliary Tract Cancer (BTC) Cohort

    For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.

    Measured: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  3. Duration of Response (DoR) in the Adenocarcinoma of the Small Intestine (ASI) Cohort

    For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.

    Measured: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  4. Duration of Response (DoR) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort

    For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.

    Measured: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  5. Duration of Response (DoR) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort

    For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.

    Measured: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  6. Duration of Response (DoR) in the Hairy Cell Leukemia (HCL) Cohort

    For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.

    Measured: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  7. Duration of Response (DoR) in the Multiple Myeloma (MM) Cohort

    For the subset of subjects who showed a confirmed response as defined for each cohort, Duration of Response (DoR) was defined as the time (in weeks) from first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever was first. If the subject did not have a documented date of progression or death, DoR was censored at the date of the last adequate assessment.

    Measured: From first documented evidence of response (the first response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  8. Progression Free Survival (PFS) in the Anaplastic Thyroid Cancer (ATC) Cohort

    Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.

    Measured: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  9. Progression Free Survival (PFS) in the Biliary Tract Cancer (BTC) Cohort

    Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.

    Measured: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  10. Progression Free Survival (PFS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort

    Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.

    Measured: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  11. Progression Free Survival (PFS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort

    Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.

    Measured: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  12. Progression Free Survival (PFS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort

    Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.

    Measured: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  13. Progression Free Survival (PFS) in the Hairy Cell Leukemia (HCL) Cohort

    Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.

    Measured: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  14. Progression Free Survival (PFS) in the Multiple Myeloma (MM) Cohort

    Progression Free Survival (PFS) was defined as the interval between the first dose of study treatment and earlier date of first radiologically documented progression or death due to any cause. If the subject did not have a documented date of progression or death, PFS was censored at the date of the last adequate assessment.

    Measured: From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  15. Overall Survival (OS) in the Anaplastic Thyroid Cancer (ATC) Cohort

    Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.

    Measured: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  16. Overall Survival (OS) in the Biliary Tract Cancer (BTC) Cohort

    Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.

    Measured: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  17. Overall Survival (OS) in the Adenocarcinoma of the Small Intestine (ASI) Cohort

    Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.

    Measured: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  18. Overall Survival (OS) in the Low Grade (WHO G1/G2) Glioma (LGG) Cohort

    Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.

    Measured: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  19. Overall Survival (OS) in the High Grade (WHO G3/G4) Glioma (HGG) Cohort

    Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.

    Measured: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  20. Overall Survival (OS) in the Hairy Cell Leukemia (HCL) Cohort

    Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.

    Measured: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  21. Overall Survival (OS) in the Multiple Myeloma (MM) Cohort

    Overall Survival (OS) was defined as the time from first dose until death due to any cause. Censoring was performed using the date of last known contact for those who were alive at the time of analysis.

    Measured: From study treatment start date until date of death from any cause, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

  22. Number of Participants With Adverse Events (AEs)

    The distribution of adverse events (AE) was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) through the monitoring of relevant clinical and laboratory safety parameters.

    Measured: From study treatment start date till 30 days safety follow-up, assessed up to 92 months (cut-off date for end of study = 10-Dec-21)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2014 (estimated)
  2. Study start12 Mar 2014
  3. Primary completion10 Dec 2021
  4. Study completion10 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
9 indications: anaplastic thyroid cancer (ATC), biliary tract cancer (BTC), gastrointestinal stromal tumor (GIST), low grade (WHO G1/G2) glioma (LGG), high grade (WHO G3/G4) glioma (HGG), non-seminomatous germ cell tumors (NSGCT)/non-germinomatous germ cell tumors (NGGCT), adenocarcinoma of the small intestine (ASI), hairy cell leukemia (HCL) and multiple myeloma (MM).
Masking
None (open label)
Enrolment
206 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02034110
Sponsor's protocol ID
117019
Other IDs
2013-001705-87, CDRB436X2201, BRF117019
Status last verified
Jul 2023
First submitted
5 Dec 2013
Last updated
21 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

  • Subbiah V, Burris HA 3rd, Kurzrock R. Revolutionizing cancer drug development: Harnessing the potential of basket trials. Cancer. 2024 Jan;130(2):186-200. doi: 10.1002/cncr.35085. Epub 2023 Nov 7.

    PubMed 37934000

  • Hicks HM, Pozdeyev N, Sams SB, Pugazhenthi U, Bales ES, Hofmann MC, McKenna LR, Schweppe RE. Fibronectin Contributes to a BRAF Inhibitor-driven Invasive Phenotype in Thyroid Cancer through EGR1, Which Can Be Blocked by Inhibition of ERK1/2. Mol Cancer Res. 2023 Sep 1;21(9):867-880. doi: 10.1158/1541-7786.MCR-22-1031.

    PubMed 37219859

  • Subbiah V, Kreitman RJ, Wainberg ZA, Gazzah A, Lassen U, Stein A, Wen PY, Dietrich S, de Jonge MJA, Blay JY, Italiano A, Yonemori K, Cho DC, de Vos FYFL, Moreau P, Fernandez EE, Schellens JHM, Zielinski CC, Redhu S, Boran A, Passos VQ, Ilankumaran P, Bang YJ. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. Nat Med. 2023 May;29(5):1103-1112. doi: 10.1038/s41591-023-02321-8. Epub 2023 Apr 14.

    PubMed 37059834

  • Kreitman RJ, Moreau P, Ravandi F, Hutchings M, Gazzah A, Michallet AS, Wainberg ZA, Stein A, Dietrich S, de Jonge MJA, Willenbacher W, De Greve J, Arons E, Ilankumaran P, Burgess P, Gasal E, Subbiah V. Dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600E mutation-positive hairy cell leukemia. Blood. 2023 Mar 2;141(9):996-1006. doi: 10.1182/blood.2021013658.

    PubMed 36108341

  • Wen PY, Stein A, van den Bent M, De Greve J, Wick A, de Vos FYFL, von Bubnoff N, van Linde ME, Lai A, Prager GW, Campone M, Fasolo A, Lopez-Martin JA, Kim TM, Mason WP, Hofheinz RD, Blay JY, Cho DC, Gazzah A, Pouessel D, Yachnin J, Boran A, Burgess P, Ilankumaran P, Gasal E, Subbiah V. Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. Lancet Oncol. 2022 Jan;23(1):53-64. doi: 10.1016/S1470-2045(21)00578-7. Epub 2021 Nov 24.

    PubMed 34838156

  • Subbiah V, Lassen U, Elez E, Italiano A, Curigliano G, Javle M, de Braud F, Prager GW, Greil R, Stein A, Fasolo A, Schellens JHM, Wen PY, Viele K, Boran AD, Gasal E, Burgess P, Ilankumaran P, Wainberg ZA. Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 2020 Sep;21(9):1234-1243. doi: 10.1016/S1470-2045(20)30321-1. Epub 2020 Aug 17.

    PubMed 32818466

  • Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, Wen PY, Zielinski C, Cabanillas ME, Urbanowitz G, Mookerjee B, Wang D, Rangwala F, Keam B. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol. 2018 Jan 1;36(1):7-13. doi: 10.1200/JCO.2017.73.6785. Epub 2017 Oct 26.

    PubMed 29072975

  • Lee EQ, Ruland S, LeBoeuf NR, Wen PY, Santagata S. Successful Treatment of a Progressive BRAF V600E-Mutated Anaplastic Pleomorphic Xanthoastrocytoma With Vemurafenib Monotherapy. J Clin Oncol. 2016 Apr 1;34(10):e87-9. doi: 10.1200/JCO.2013.51.1766. Epub 2014 Aug 4. No abstract available.

    PubMed 25092772

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dabrafenib and Trametinib in people with Cancer, run by Novartis Pharmaceuticals at 41 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in United States, France, Germany, Austria, Netherlands and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) in the Anaplastic Thyroid Cancer (ATC) Cohort (time frame: From study treatment start date until first documented complete response or partial response, assessed up to 78 months (cut-off date for FDA Submission = 14-Sep-20) and up to 92 months (cut-off date for end of study = 10-Dec-21)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02034110, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2023.

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