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Locally Advanced Pancreatic CarcinomaPhase 2NCT04390243

Binimetinib and Encorafenib for the Treatment of Pancreatic Cancer in Patients With a Somatic BRAF V600E Mutation

A Phase 2 study testing Binimetinib and Encorafenib in people with Locally Advanced Pancreatic Carcinoma and Metastatic Pancreatic Carcinoma, run by Academic and Community Cancer Research United at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial studies the side effects and how well the combination of binimetinib and encorafenib work in treating patients with pancreatic cancer with a somatic BRAF V600E mutation. Binimetinib and encorafenib 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
What is being tested?
Binimetinib and Encorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
5 sitesUnited States
Study dates
16 Nov 2020to 1 Nov 2023
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

  • PRE-REGISTRATION:
  • Histological confirmation of a pancreatic malignancy as confirmed by the local pathology lab
  • Patients whose disease has progressed on (or who were intolerant of) at least one line of therapy for metastatic disease
  • Patients whose disease has recurred with metastatic disease =< 12 weeks of completion of neoadjuvant or adjuvant systemic chemotherapy; or patients with locally advanced disease whose disease progressed to metastatic disease on, or =< 12 weeks after completion of systemic chemotherapy would also be eligible
  • Provide informed written consent =< 28 days prior to pre-registration
  • Central electronic/paper confirmation of the presence of a BRAF V600E mutation. This review is mandatory prior to pre-registration to confirm eligibility. Results from a Clinical Laboratory Improvement Act (CLIA)/College of American Pathologists (CAP) certified testing lab (commercial or institutional) that confirm the presence of a BRAF V600E mutation in the patient's tumor must be submitted for central review
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  • REGISTRATION: NOTE: Registration must occur =< 30 days after pre-registration
  • Confirmation of the presence of BRAF V600E mutation in the patient's tumor
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2. (Form is available on the Academic and Community Cancer Research United [ACCRU] web site)
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to registration)
  • Platelet count >= 75,000/mm^3 (obtained =< 14 days prior to registration)
  • Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration)
  • Aspartate transaminase (AST) =< 2.5 x ULN; in participants with liver metastases =< 5 x ULN (obtained =< 14 days prior to registration)
  • Aminotransferase (ALT) =< 2.5 x ULN; in participants with liver metastases =< 5 x ULN (obtained =< 14 days prior to registration)
  • Calculated creatinine clearance must be >= 45 ml/min using the Cockcroft Gault formula (obtained =< 14 days prior to registration)
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study). Note: During the active monitoring phase of a study (i.e., active treatment), participants must be willing to return to the consenting institution for follow-up
  • Ability to swallow the investigational product tablets and capsules
  • Willing to provide tissue and blood samples for correlative research purposes

Who cannot join

  • REGISTRATION:
  • Patients whose tumor harbors a BRAF non-V600E mutation or a BRAF fusion
  • Prior therapy with BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib) and/or a MEK inhibitor (e.g., binimetinib, trametinib, cobimetinib)
  • Known hypersensitivity or contraindication to any component of binimetinib or encorafenib or their excipients
  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant women
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  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • NOTE: Female participants of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, and to not donate ova from screening until 30 days after the last dose of study drug
  • NOTE: Male participants must agree to use methods of contraception that are highly effective or acceptable, and to not donate sperm from screening until 90 days after the last dose of study drug
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy. NOTE: Patients known to be human immunodeficiency virus ( HIV) positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) < 6 months prior to registration
  • Left ventricular ejection fraction (LVEF) =< 50% as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)
  • Uncontrolled hypertension defined as persistent systolic blood pressure >= 150/100 mmHg or diastolic blood pressure >= 100 mmHg despite current therapy
  • Triplicate average baseline corrected QT (QTc) interval >= 480 ms
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Patients who have had another active malignancy within the past two years are ineligible EXCEPT FOR patients with cervical cancer in situ, in situ carcinoma of the bladder, non-melanoma carcinoma of the skin, or patients who have had therapy with curative intent for breast or prostate cancer, but remain on adjuvant hormonal therapy
  • Received anticancer therapy including chemotherapy, immunotherapy, or antineoplastic biologic therapy (e.g., erlotinib, cetuximab, bevacizumab etc.), =<14 days (=< 28 days for an antibody-based therapy) prior to registration
  • Patients who have undergone major surgery (e.g., in-patient procedures) =< 6 weeks prior to registration or who have not recovered from side effects of such procedure
  • Patients who have had radiotherapy =< 14 days prior to registration or who have not recovered from side effects of such procedure. NOTE: Palliative radiation therapy must be complete 7 days prior to the first dose of study treatment
  • Patient has not recovered to =< grade 1 from toxic effects of prior therapy before registration. EXCEPTIONS: Stable chronic conditions (=< grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies)
  • Uncontrolled or symptomatic brain metastases or leptomeningeal carcinomatosis that are not stable, require steroids, are potentially life-threatening or have required radiation =< 28 days prior to registration.
  • NOTE: Patients with previously treated brain metastases may participate provided they are stable (e.g., without evidence of progression by radiographic imaging for =< 28 days prior to registration and neurologic symptoms have returned to baseline), and have no evidence of new or enlarging brain metastases or central nervous system (CNS) edema, and does not require steroids at least 7 days before the first dose of study treatment.
  • Impairment of gastrointestinal function or disease which may significantly alter the absorption of study drug (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, small bowel resection with decreased intestinal absorption), or recent (=< 12 weeks) history of a partial or complete bowel obstruction, or other condition that will interfere significantly with the absorption or oral drugs
  • Known history of acute or chronic pancreatitis
  • Concurrent neuromuscular disorder that is associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amytrophic lateral sclerosis, spinal muscular atrophy)
  • History or current evidence of RVO or current risk factors for retinal vein occlusion (RVO) (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease
  • Current use of prohibited medication (including herbal medications, supplements, or foods), or use of prohibited medication =< 7 days prior to registration
  • History of thromboembolic or cerebrovascular events =< 12 weeks prior to registration. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli.
  • NOTE: Patients with either deep vein thrombosis or pulmonary emobli that do not result in hemodynamic instability are allowed to enroll as long as they are on a stable dose of anticoagulants for =< 4 weeks prior to registration
  • NOTE: Patients with thromboembolic events related to indwelling catheters or other procedures may register
  • Evidence of hepatitis B Virus (HBV) or hepatitis C Virus (HCV) infection.
  • NOTE: Patients with laboratory evidence of cleared HBV or HCV infection may register.
  • NOTE: Patients with no prior history of HBV infection who have been vaccinated against HBV and who have a positive antibody against hepatitis B surface antigen as the only evidence of prior exposure may register

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Mayo Clinic in Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: BrafPanc: A Phase II Trial of Binimetinib in Combination With Encorafenib in Patients With Pancreatic Malignancies and a Somatic BRAFV600E Mutation

This phase II trial studies the side effects and how well the combination of binimetinib and encorafenib work in treating patients with pancreatic cancer with a somatic BRAF V600E mutation. Binimetinib and encorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and encorafenib may work better compared to the usual treatment in treating patients with pancreatic cancer and a somatic BRAF V600E mutation.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the efficacy of the combination of binimetinib and encorafenib as >= 2nd line of treatment for patients with metastatic pancreatic cancer with BRAF V600E mutation.

SECONDARY OBJECTIVES:

  1. To determine in patients treated with the combination of binimetinib and encorafenib as >= 2nd line of treatment for patients with metastatic pancreatic cancer with BRAF V600E mutation:

Ia. The median progression-free survival. Ib. The median overall survival. Ic. Duration of response. Id. Time to response. Ie. The safety and tolerability.

OUTLINE:

Patients receive encorafenib orally (PO) once daily (QD) and binimetinib PO twice daily (BID) on days 1-25. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Being tested
Binimetinib, Encorafenib
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • BinimetinibDrug

    Also called ARRY-162, ARRY-438162, MEK162, Mektovi

    Given PO

  • EncorafenibDrug

    Also called Braftovi, LGX 818, LGX-818, LGX818

    Given PO

Study groups in NCT04390243
Study groupRoleWhat they receive
Treatment (encorafenib, binimetinib)ExperimentalPatients receive encorafenib PO QD and binimetinib PO BID on days 1-25. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Binimetinib; Drug: Encorafenib

What is being measured

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

  1. Objective Response Rate (ORR) at 24 Weeks

    An objective response is defined as a complete or partial response with a confirmation scan not less than 4 weeks after the initial scan. Disease status will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria. The final ORR point estimate and corresponding 95% confidence interval will be reported.

    Measured: 24 weeks

Secondary outcomes (5)

  1. Progression-free Survival (PFS)

    Progression-free survival is defined as the time from registration to clinical or radiographic disease progression or death, whichever occurs first, as defined by RECIST 1.1 criteria. PFS will be estimated using the Kaplan-Meier method. The median PFS and corresponding 95% confidence interval will be reported.

    Measured: 25 months

  2. Overall Survival

    Overall survival (OS) is defined as the time from registration to death from any cause. OS will be estimated using the Kaplan-Meier method. The median overall survival and corresponding 95% confidence interval will be reported.

    Measured: 25 months

  3. Duration of Response

    Duration of response is defined as the duration of time from first documentation of an objective response to the earliest date disease progression is documented or death from any cause. Duration of response will be estimated using the Kaplan-Meier method. The median duration of response and corresponding 95% confidence interval will be reported.

    Measured: 12 months

  4. Time to Response

    Time to response is defined as the duration of time from registration to the first documentation of an objective response. Time to response will be estimated using the Kaplan-Meier method. The median time to response and corresponding 95% confidence interval will be reported.

    Measured: 25 months

  5. Number of Patients With Grade 3+ Adverse Events

    Adverse Events as defined by National Institute of Health (NIH) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. All patients who have initiated treatment will be considered evaluable for adverse event analyses. The rate of patients experiencing a grade 3+ adverse event will be reported.

    Measured: 25 months

Timeline

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

  1. First posted15 May 2020
  2. Study start16 Nov 2020
  3. Primary completion1 Nov 2023
  4. Study completion1 Nov 2023

Why it stopped: Slow accrual

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
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04390243
Sponsor's protocol ID
ACCRU-GI-1907
Other IDs
NCI-2020-02972, ACCRU-GI- 1907, P30CA015083
Status last verified
Sep 2023
First submitted
12 May 2020
Last updated
6 May 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Binimetinib and Encorafenib in people with Locally Advanced Pancreatic Carcinoma and Metastatic Pancreatic Carcinoma, run by Academic and Community Cancer Research United at 5 sites 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 21 inclusion and 36 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 6 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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 23 Jan 2024). 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?

Objective Response Rate (ORR) at 24 Weeks (time frame: 24 weeks). 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 NCT04390243.

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 6 May 2024.

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