ALK Fusion Protein ExpressionPhase 2NCT02587650
Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma
A Phase 2 study testing Capmatinib, Ceritinib and Entrectinib in people with ALK Fusion Protein Expression and BRAF wt Allele, run by University of California, San Francisco at 1 site in United States.
Trial summary
This phase II trial studies how well capmatinib, ceritinib, regorafenib, or entrectinib work in treating patients with BRAF/NRAS wild-type stage III-IV melanoma. Capmatinib, ceritinib, regorafenib, or entrectinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ALK Fusion Protein Expression, BRAF wt Allele, Invasive Skin Melanoma
- What is being tested?
- Capmatinib, Ceritinib and Entrectinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Mar 2015to 12 Jul 2018
- 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
- CAPMATINIB INCLUSION CRITERIA:
- Ability to understand a written informed consent document, and the willingness to sign it
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Life expectancy >= 12 weeks
- Histologically or cytologically confirmed invasive melanoma
- Unresectable stage III or stage IV melanoma by clinical or radiographic criteria
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- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
- Documentation of absence of activating and targetable BRAF or NRAS point mutations
- Presence of an oncogenic kinase fusion involving MET, confirmed by assay by a Clinical Laboratory Improvement Act (CLIA)-approved laboratory
- Prior treatment with at least one Food and Drug Administration (FDA)-approved drug for unresectable/metastatic melanoma; patients who are treatment-naive but who refuse available standard options and prefer to enroll on this study as their first line of treatment after a thorough informed consent process will be eligible at the discretion of the treating physician
- Resolution of all acute toxic effects (excluding alopecia) of prior radiotherapy, chemotherapy or surgical procedures to Common Terminology Criteria for Adverse Events (CTCAE) v4.03 grade =< 1
- Absolute neutrophil count >= 1,500/mm^3
- Platelets >= 75,000/ microliters (mcL)
- Hemoglobin >= 9 g/dL (transfusions are allowed)
- Total bilirubin =< 1.5 x upper limit of normal (ULN); patients with Gilbert?s syndrome may be included if total bilirubin =< 3 x ULN or direct bilirubin =< 1.5 x ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN if no liver metastases are present? =< 5 x ULN if liver metastases are present
- Alkaline phosphatase (ALP) =< 5 x ULN
- Serum amylase =< grade 2 and asymptomatic; patients with grade 1 or 2 serum amylase at the beginning of the study must be confirmed to have no signs and/or symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.)
- Serum lipase =< ULN
- Creatinine OR creatinine clearance within normal limits > 40 mL/min (calculated by Cockgraft-Gault) for patients with creatinine levels above ULN
- Serum potassium, calcium (corrected for serum albumin), magnesium, phosphorus within normal limits with or without supplementation
- CERITINIB INCLUSION CRITERIA:
- Ability to understand a written informed consent document, and the willingness to sign it
- ECOG performance status 0-1
- Life expectancy >= 12 weeks
- Histologically or cytologically confirmed invasive melanoma
- Unresectable stage III or stage IV melanoma by clinical or radiographic criteria
- Measurable disease by RECIST v1.1
- Documentation of absence of activating and targetable BRAF or NRAS point mutations
- Presence of an oncogenic kinase fusion involving ALK, confirmed by assay by a CLIA-approved laboratory
- Prior treatment with at least one FDA-approved drug for unresectable/metastatic melanoma; patients who are treatment-naive but who refuse available standard options and prefer to enroll on this study as their first line of treatment after a thorough informed consent process will be eligible at the discretion of the treating physician
- Resolution of all acute toxic effects (excluding alopecia) of prior radiotherapy, chemotherapy or surgical procedures to CTCAE v4.03 grade =< 1
- Absolute neutrophil count >= 1.5 x 10^9/L
- Platelets >= 75 x 10^9/L
- Hemoglobin >= 8 g/dL (transfusions are allowed)
- Total bilirubin =< 1.5 x upper limit of normal (ULN); patients with Gilbert?s syndrome may be included if total bilirubin =< 3 x ULN and direct bilirubin =< 1.5 x ULN
- AST (SGOT) and ALT (SGPT) =< 3 x ULN if no liver metastases are present? =< 5 x ULN if liver metastases are present
- Alkaline phosphatase (ALP) =< 5 x ULN
- Serum amylase =< 2 x ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 175 mg/dL (=< 9.8 mmol/L)
- Creatinine OR creatinine clearance < 1.5 mg/dL >= 30 mL/min (calculated by Cockgraft-Gault) for patients with creatinine levels above ULN
- Serum potassium, calcium (corrected for serum albumin), magnesium, phosphorus within normal limits with or without supplementation
- REGORAFENIB INCLUSION CRITERIA:
- Ability to understand a written informed consent document, and the willingness to sign it
- ECOG performance status 0-1
- Life expectancy >= 12 weeks
- Histologically or cytologically confirmed invasive melanoma
- Unresectable stage III or stage IV melanoma by clinical or radiographic criteria
- Measurable disease by RECIST v1.1
- Documentation of absence of activating and targetable BRAF or NRAS point mutations
- Presence of an oncogenic kinase fusion involving BRAF or RET, confirmed by assay by a CLIA-approved laboratory
- Prior treatment with at least one FDA-approved drug for unresectable/metastatic melanoma; patients who are treatment-naive but who refuse available standard options and prefer to enroll on this study as their first line of treatment after a thorough informed consent process will be eligible at the discretion of the treating physician
- Resolution of all acute toxic effects (excluding alopecia) of prior radiotherapy, chemotherapy or surgical procedures to CTCAE v4.03 grade =< 1
- Absolute neutrophil count >= 1,500/mm^3
- Platelets >= 100,000/mm^3
- Hemoglobin >= 9 g/dL
- Total bilirubin =< 1.5 x upper limit of normal (ULN); patients with Gilbert?s syndrome may be included if total bilirubin =< 3 x ULN or direct bilirubin =< 1.5 x ULN
- AST (SGOT) and ALT (SGPT) =< 2.5 x ULN if no liver metastases are present? =< 5 x ULN if liver metastases are present
- Alkaline phosphatase (ALP) =< 2.5 x ULN if no liver metastases are present; =< 5 x ULN if bone or liver metastases are present
- Creatinine OR creatinine clearance =< 1.5 x ULN; > 40 mL/min (calculated by Cockgraft-Gault) for patients with creatinine levels above ULN
- Serum potassium, calcium (corrected for serum albumin), magnesium, phosphorus within normal limits with or without supplementation
- International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x ULN (patients who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate, provided that no prior evidence of underlying abnormality in coagulation parameters exists; close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is predose as defined by the local standard of care)
- ENTRECTINIB INCLUSION CRITERIA:
- Ability to understand a written informed consent document, and the willingness to sign it
- ECOG performance status 0-2
- Histologically or cytologically confirmed invasive melanoma
- Unresectable stage III or stage IV melanoma by clinical or radiographic criteria
- Measurable disease by RECIST v1.1
- Patients with central nervous system (CNS) involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously-treated and controlled, are allowed; the use of seizure prophylaxis is allowed as long as patients are taking non enzyme-inducing anti-epileptic drugs (non-EIAEDs); if patients were previously on EIAEDs and these have been discontinued, they must have been discontinued for at least 2 weeks prior to the start of entrectinib treatment; if patients require an anti-epileptic medication, a CYP3A4 non-EIAED can be used such as levetiracetam, valproic acid, gabapentin, topiramate, or lacosamide; moderate inducers of CYP450, such as dexamethasone or other glucocorticoids, may be used at the discretion of the investigator; patients requiring steroids must be at a stable or decreasing doses for at least 2 weeks prior to the start of entrectinib treatment
- Documentation of absence of activating and targetable BRAF or NRAS point mutations
- Presence of an oncogenic kinase fusion involving ROS1 or NTRK1/2/3, confirmed by assay by a CLIA-approved laboratory
- Prior treatment with at least one FDA-approved drug for unresectable/metastatic melanoma; patients who are treatment-naive but who refuse available standard options and prefer to enroll on this study as their first line of treatment after a thorough informed consent process will be eligible at the discretion of the treating physician
- Resolution of all acute toxic effects (excluding alopecia) of prior radiotherapy, chemotherapy or surgical procedures to CTCAE v4.03 grade =< 1
- Absolute neutrophil count >= 1,000/mm^3
- Platelets >= 75,000/mcL
- Hemoglobin >= 8 g/dL (transfusions are allowed)
- Total bilirubin =< 1.5 x upper limit of normal (ULN); patients with Gilbert?s syndrome may be included if total bilirubin =< 3 x ULN or direct bilirubin =< 1.5 x ULN
- AST (SGOT) and ALT (SGPT) =< 3.0 x ULN if no liver metastases are present? =< 5 x ULN if liver metastases are present
- Creatinine OR creatinine clearance within normal limits; > 40 mL/min (calculated by Cockgraft-Gault) for patients with creatinine levels above ULN
Who cannot join
- CAPMATINIB EXCLUSION CRITERIA: Uveal melanoma
- CAPMATINIB EXCLUSION CRITERIA: Current participation in another therapeutic clinical trial
- CAPMATINIB EXCLUSION CRITERIA: Inability to swallow intact tablets or capsules
- CAPMATINIB EXCLUSION CRITERIA: Previously identified allergy or hypersensitivity to components of capmatinib formulation (crospovidone, mannitol, microcrystalline cellulose, povidone, sodium lauryl sulfate, magnesium stearate, colloidal silicon dioxide, and various coating premixes)
- CAPMATINIB EXCLUSION CRITERIA: Diagnosis of concurrent malignancy or previous malignancy within 3 years before study drug administration (exceptions are superficial skin cancers, or any in situ cancers deemed surgically resected, cured and not requiring systemic therapy, and indolent malignancies that currently do not require treatment)
- CAPMATINIB EXCLUSION CRITERIA: Prior treatment with the following antineoplastic therapies within the following time frame:
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- Any prior treatment with capmatinib, crizotinib, or any other cMET or hepatocyte growth factor (HGF) inhibitor
- Thoracic radiotherapy to lung fields =< 4 weeks prior to starting capmatinib; for all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy =< 2 weeks prior to starting capmatinib; palliative radiotherapy for bone lesions =< 2 weeks prior to starting capmatinib is allowed
- Receipt of any anticancer or investigational agent within 4 weeks or =< 5 half-lives of the agent (whichever is longer) prior to the first dose of capmatinib; if previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 4 weeks before the first dose of capmatinib
- CAPMATINIB EXCLUSION CRITERIA: Major surgery (e.g., intrathoracic, intraabdominal or intrapelvic) within 4 weeks prior (2 weeks for resection of brain metastases) to starting capmatinib; video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and patients can be enrolled in the study >= 1 week after the procedure
- CAPMATINIB EXCLUSION CRITERIA: Patients receiving treatment with medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of capmatinib treatment and for the duration of the study:
- Strong and moderate inhibitors of CYP3A4
- Strong inducers of CYP3A4
- Proton pump inhibitors (PPI)
- CAPMATINIB EXCLUSION CRITERIA: Patients on unstable or increasing doses of corticosteroids; if patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms other than CNS related, dose must have been stabilized or decreasing for at least 5 days before first dose of capmatinib
- CAPMATINIB EXCLUSION CRITERIA: Presence or history of carcinomatous meningitis
- CAPMATINIB EXCLUSION CRITERIA: Known symptomatic brain metastases requiring increasing doses of steroid to manage CNS symptoms within 2 weeks prior to study entry
- Patients with asymptomatic brain metastases may be enrolled at the discretion of the sponsor as long as the patient is stable and has not required increasing dose of steroids to manage CNS symptoms for at least 2 weeks prior to study enrollment
- Patients requiring seizure prophylaxis must be taking non-enzyme-inducing anti-epileptic drugs (non-EIAED); if patients were previously on EIAEDs and these have been discontinued, they must be discontinued for at least 1 weeks prior to capmatinib administration; if patients re
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94115
About this study
Official title: A Phase II Trial of Targeted Kinase Fusion Inhibition in Unresectable Stage III/IV BRAF/NRAS Wild-Type Melanoma
This phase II trial studies how well capmatinib, ceritinib, regorafenib, or entrectinib work in treating patients with BRAF/NRAS wild-type stage III-IV melanoma. Capmatinib, ceritinib, regorafenib, or entrectinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the clinical activity of tyrosine kinase inhibitors matched to the tumor-specific fusion kinase in patients with metastatic melanoma.
SECONDARY OBJECTIVES:
- To estimate tumor stability in melanoma patients treated with kinase inhibitors matched to the tumor-specific fusion kinase.
II. To estimate survival in melanoma patients treated with kinase inhibitors matched to the tumor-specific fusion kinase.
III. To examine the safety and tolerability of kinase inhibitors in patients with melanoma with a fusion kinase.
TERTIARY OBJECTIVES:
- To explore molecular mechanisms of resistance for patients who progress on therapy.
OUTLINE: Patients are assigned to 1 of 4 arms.
ARM A: Patients with MET fusion receive capmatinib orally (PO) twice daily (BID) on day 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
ARM B: Patients with ALK fusion receive ceritinib PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
ARM C: Patients with RET or BRAF fusion receive regorafenib PO QD on day 1-21. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
ARM D: Patients with NTRK1, NTRK2, NTRK3, or ROS1 fusion receive entrectinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, patients are followed up within 30 days and then periodically.
- Conditions
- ALK Fusion Protein Expression, BRAF wt Allele, Invasive Skin Melanoma, MET Fusion Gene Positive, NRAS wt Allele, NTRK1 Fusion Positive
- Being tested
- Capmatinib, Ceritinib, Entrectinib, Laboratory Biomarker Analysis, Regorafenib
- Medical subject headings
- Noonan Syndrome 6, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapmatinibDrug
Also called INC-280, INC280, INCB 28060, INCB028060
Given PO
CeritinibDrug
Also called LDK 378, LDK378, Zykadia
Given PO
EntrectinibDrug
Also called RXDX-101
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
RegorafenibDrug
Also called BAY 73-4506, Stivarga
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm A (capmatinib) | Experimental | Patients with MET fusion receive capmatinib PO BID on day 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity. Receives: Drug: Capmatinib; Other: Laboratory Biomarker Analysis |
| Arm B (ceritinib) | Experimental | Patients with ALK fusion receive ceritinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity. Receives: Drug: Ceritinib; Other: Laboratory Biomarker Analysis |
| Arm C (regorafenib) | Experimental | Patients with RET or BRAF fusion receive regorafenib PO QD on day 1-21. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Regorafenib |
| Arm D (entrectinib) | Experimental | Patients with NTRK1, NTRK2, NTRK3, OR ROS1 fusion receive entrectinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity. Receives: Drug: Entrectinib; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed Overall Response Rate (ORR)
Defined as a complete or partial response as per Response Evaluation Criteria in Solid Tumors version 1.1 criteria with confirmatory measurements a minimum of 4 weeks after the response-defining determination. Analysis of study results will include ORR estimations of ALK, NTRK, ROS1, RET, MET, and BRAF rearrangement-positive patients.
Measured: 24 weeks
Secondary outcomes (4)
Clinical Benefit Rate (CBR)
Clinical benefit rate is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) for > 24 weeks using the same RECIST 1.1 decision matrix used to calculate ORR. The CBR will be estimated for each arm along with a 95% confidence interval
Measured: Up to 2 years
Overall Survival
Overall defined as the time from treatment start to the progression or death and overall survival defined as the time from treatment start to death will be estimated using Kaplan-Meier methodology.
Measured: From treatment start to death, assessed up to 2 years
Progression Free Survival
Progression free survival (PFS) defined as the time from treatment start to the progression or death and overall survival defined as the time from treatment start to death will be estimated using Kaplan-Meier methodology
Measured: up to 2 years
Evaluation of the Adverse Effect Profile of Each Kinase Inhibitor
Frequencies of toxicities will be tabulated according to CTCAE v4.03 to assess drug safety and tolerability
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2015 (estimated)
- Study start26 Mar 2015
- Primary completion12 Jul 2018
- Study completion12 Jul 2018
Why it stopped: Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ALK Fusion Protein ExpressionStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adil Daud, University of California, San Francisco
- Investigators
- Adil Daud, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02587650
- Sponsor's protocol ID
- 14859
- Other IDs
- NCI-2017-01421
- Status last verified
- Jan 2020
- First submitted
- 23 Oct 2015
- Last updated
- 27 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Targeted Kinase Fusion Inhibition in Unresectable Stage III/IV BRAF/NRAS Wild-Type Melanoma
- ClinicalTrials.gov ID
- NCT02587650
- Acronym / sponsor ID
- 14859
- Conditions
- ALK Fusion Protein Expression, BRAF wt Allele, Invasive Skin Melanoma, MET Fusion Gene Positive, NRAS wt Allele, NTRK1 Fusion Positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 26 Mar 2015 (actual)
- Primary completion
- 12 Jul 2018 (actual)
- Study completion
- 12 Jul 2018 (actual)
- First posted
- 27 Oct 2015 (estimated)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well capmatinib, ceritinib, regorafenib, or entrectinib work in treating patients with BRAF/NRAS wild-type stage III-IV melanoma. Capmatinib, ceritinib, regorafenib, or entrectinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the clinical activity of tyrosine kinase inhibitors matched to the tumor-specific fusion kinase in patients with metastatic melanoma.
SECONDARY OBJECTIVES:
- To estimate tumor stability in melanoma patients treated with kinase inhibitors matched to the tumor-specific fusion kinase.
II. To estimate survival in melanoma patients treated with kinase inhibitors matched to the tumor-specific fusion kinase.
III. To examine the safety and tolerability of kinase inhibitors in patients with melanoma with a fusion kinase.
TERTIARY OBJECTIVES:
- To explore molecular mechanisms of resistance for patients who progress on therapy.
OUTLINE: Patients are assigned to 1 of 4 arms.
ARM A: Patients with MET fusion receive capmatinib orally (PO) twice daily (BID) on day 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
ARM B: Patients with ALK fusion receive ceritinib PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
ARM C: Patients with RET or BRAF fusion receive regorafenib PO QD on day 1-21. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
ARM D: Patients with NTRK1, NTRK2, NTRK3, or ROS1 fusion receive entrectinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, patients are followed up within 30 days and then periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm A (capmatinib) | Experimental | Drug: Capmatinib, Other: Laboratory Biomarker AnalysisPatients with MET fusion receive capmatinib PO BID on day 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity. |
| Arm B (ceritinib) | Experimental | Drug: Ceritinib, Other: Laboratory Biomarker AnalysisPatients with ALK fusion receive ceritinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity. |
| Arm C (regorafenib) | Experimental | Other: Laboratory Biomarker Analysis, Drug: RegorafenibPatients with RET or BRAF fusion receive regorafenib PO QD on day 1-21. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity. |
| Arm D (entrectinib) | Experimental | Drug: Entrectinib, Other: Laboratory Biomarker AnalysisPatients with NTRK1, NTRK2, NTRK3, OR ROS1 fusion receive entrectinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (80 listed)
- CAPMATINIB INCLUSION CRITERIA:
- CERITINIB INCLUSION CRITERIA:
- REGORAFENIB INCLUSION CRITERIA:
- ENTRECTINIB INCLUSION CRITERIA:
Key exclusion criteria (19 listed)
- CAPMATINIB EXCLUSION CRITERIA: Uveal melanoma
- CAPMATINIB EXCLUSION CRITERIA: Current participation in another therapeutic clinical trial
- CAPMATINIB EXCLUSION CRITERIA: Inability to swallow intact tablets or capsules
- CAPMATINIB EXCLUSION CRITERIA: Previously identified allergy or hypersensitivity to components of capmatinib formulation (crospovidone, mannitol, microcrystalline cellulose, povidone, sodium lauryl sulfate, magnesium stearate, colloidal silicon dioxide, and various coating premixes)
- CAPMATINIB EXCLUSION CRITERIA: Diagnosis of concurrent malignancy or previous malignancy within 3 years before study drug administration (exceptions are superficial skin cancers, or any in situ cancers deemed surgically resected, cured and not requiring systemic therapy, and indolent malignancies that currently do not require treatment)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapmatinibAlso: INC-280, INC280, INCB 28060, INCB028060Given PO | Drug | Arm A (capmatinib) |
| CeritinibAlso: LDK 378, LDK378, ZykadiaGiven PO | Drug | Arm B (ceritinib) |
| EntrectinibAlso: RXDX-101Given PO | Drug | Arm D (entrectinib) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm A (capmatinib), Arm B (ceritinib), Arm C (regorafenib), Arm D (entrectinib) |
| RegorafenibAlso: BAY 73-4506, StivargaGiven PO | Drug | Arm C (regorafenib) |
Primary outcome
Confirmed Overall Response Rate (ORR)
Time frame: 24 weeks
Defined as a complete or partial response as per Response Evaluation Criteria in Solid Tumors version 1.1 criteria with confirmatory measurements a minimum of 4 weeks after the response-defining determination. Analysis of study results will include ORR estimations of ALK, NTRK, ROS1, RET, MET, and BRAF rearrangement-positive patients.
4 secondary outcomes
Clinical Benefit Rate (CBR)
Time frame: Up to 2 years
Overall Survival
Time frame: From treatment start to death, assessed up to 2 years
Progression Free Survival
Time frame: up to 2 years
Evaluation of the Adverse Effect Profile of Each Kinase Inhibitor
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adil Daud principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Capmatinib, Ceritinib and Entrectinib in people with ALK Fusion Protein Expression and BRAF wt Allele, run by University of California, San Francisco at 1 site in United States.
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 80 inclusion and 19 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: stopped early, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 27 Jan 2020). 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?
Confirmed Overall Response Rate (ORR) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jan 2020.