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Recurrent MelanomaPhase 1NCT02145910

Vemurafenib Combined With Whole Brain Radiation Therapy or Radiosurgery in Patients With BRAF Mutation-Positive Melanoma and Brain Metastases

A Phase 1 study testing Vemurafenib, Whole-brain radiation therapy (WBRT) and Radiosurgery (SRS) in people with Recurrent Melanoma and Stage IV Melanoma, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I trial studies the best dose of vemurafenib when combined with whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) in patients with v-raf murine sarcoma viral oncogene homolog B (BRAF) mutation-positive melanoma and brain metastases. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Vemurafenib, Whole-brain radiation therapy (WBRT) and Radiosurgery (SRS)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Start not givento Jun 2019
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Age ≥ 18 years
  • Histological confirmed melanoma (prior diagnosis okay)
  • BRAFV600 mutation positive (cobas 4800 BRAFV600 mutation test)
  • ECOG performance status 0 or 1
  • Craniotomy resection is allowed (a minimum 2 weeks recovery time from surgery to initiation of protocol therapy)
  • Radiographic evidence of brain metastasis
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  • Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
  • Adequate organ function:
  • WBC ≥ 2000/uL
  • ANC ≥ 1000/uL
  • Platelets ≥ 75 x 103/uL
  • Hemoglobin ≥ 9 g/dL (≥ 80 g/L; may be transfused)
  • Creatinine ≤ 2.0 x ULN OR 24-hour creatinine clearance >= 50 ml/min
  • AST/ALT ≤ 2.5 x ULN for patients without liver metastasis, ≤ 5 times for liver metastases
  • Bilirubin ≤ 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  • Total serum calcium (corrected for serum albumin) or ionized calcium ≥ lower limit of normal (LLN)
  • Serum potassium ≥ LLN
  • Serum sodium ≥ LLN
  • Serum albumin ≥ LLN or 3g/dl
  • Patients with any elevated Alkaline Phosphatase due to bone metastases can be enrolled
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. Women of potential child bearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as:
  • Amenorrhea ≥ 12 consecutive months without another cause, or
  • For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level ≥ 35 mIU/mL.
  • Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.
  • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of radiation.
  • Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized.
  • Specific eligibility criteria for the two arms:
  • Arm A (WBRT and Vemurafenib):
  • Patients have 5 or more brain metastases, or patients have any brain metastases exceeding the limit for SRS (maximum diameter is > 4 cm).
  • OR Patient has only one brain metastasis and completely resected, the resection cavity is > 5 cm in diameter.
  • Arm B (SRS and Vemurafenib):
  • Patients have 4 or fewer brain metastases. All the brain metastases are ≤ 4 cm in diameter.
  • Patients have only one brain metastasis and completely resected, the resection cavity is ≤ 5 cm in diameter.
  • OR If a patient is found to have progression of brain metastases that exceed 4 cm in diameter based on the MRI scan on the day of SRS procedure, the patient should be re-assigned to WBRT arm or withdrawn from the study. The study PI should be notified.
  • OR If a patient is found to have progression of brain metastases that exceed 4 lesions based on the MRI scan on the day of the SRS procedure, the patient can either receive SRS to all the lesions (up to 10 lesions), be re-assigned to WBRT arm, or be withdrawn from the study per the treating physician. The study PI should be notified.

Who cannot join

  • Leptomeningeal involvement
  • Cardiac disease: Congestive heart failure > class II. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • Pregnancy or breastfeeding
  • Documented history of cranial hemorrhage
  • Concurrent administration of any anticancer therapies other than those administered in the study
  • Treatment with any cytotoxic, investigational drug, or targeted therapy within 2 weeks prior to the protocol treatment.
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  • Craniotomy within 2 weeks of protocol treatment.
  • Prior treatment with other BRAF or MEK inhibitors
  • Patients who had prior brain radiation. However, prior WBRT is allowed in Arm B.
  • QTc > 450 ms
  • Patients have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated basal or squamous cell carcinoma of skin, superficial bladder cancer or carcinoma in situ of cervix, AJCC (version 7.0) stage 0 or I breast cancer, AJCC (version 7.0) stage I, or II prostate cancer.

About this study

Official title: Phase I Study of Vemurafenib Combined With Whole Brain Radiation Therapy (WBRT) or Radiosurgery (SRS) for Melanoma Patients With BRAF Mutation Presented With Brain Metastases

This phase I trial studies the best dose of vemurafenib when combined with whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) in patients with v-raf murine sarcoma viral oncogene homolog B (BRAF) mutation-positive melanoma and brain metastases. Radiation therapy is an effective treatment for patients with brain metastases. Patients with multiple metastases are typically treated with WBRT. For patients with a few metastases, SRS alone can be used. Vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Combining radiation treatment with vemurafenib for melanoma patients with brain metastases may result in improved local control and prolonged survival.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of vemurafenib when combined with WBRT or SRS and determine a recommended phase II dose of vemurafenib to be used with WBRT or SRS in patients with brain metastases from melanoma.

SECONDARY OBJECTIVES:

  1. To determine local control rates of the brain metastases in each arm. II. To determine the rates of developing of new brain metastases in each arm. III. To determine the response of extracranial disease. IV. To determine the overall survival rate and progression free survival rate. V. To determine the safety and tolerability of each arm.

OUTLINE: This is a dose-escalation study of vemurafenib. Patients are assigned to 1 of 2 arms based on the number and size of brain metastasis.

All patients receive vemurafenib orally (PO) twice daily (BID) beginning 3-5 days before the start of radiation therapy and continuing in the absence of disease progression or unacceptable toxicity.

ARM A: Patients undergo WBRT once daily (QD) for 10 doses.

ARM B: Patients undergo SRS (gamma knife, tomotherapy, cyberknife, or megavoltage linear accelerator [LINAC] radiation therapy) on day 1.

After completion of study therapy, patients are followed up on weeks 5 or 7, 9 and 13, and then on months 4, 6, 9, and 12.

Being tested
Vemurafenib, Whole-brain radiation therapy (WBRT), Radiosurgery (SRS)
Medical subject headings
Melanoma, Brain Neoplasms

What participants receive

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

  • VemurafenibDrug

    Also called Zelboraf

    Given PO

  • Whole-brain radiation therapy (WBRT)Radiation

    Also called WBRT, whole brain radiotherapy, whole-brain radiotherapy

    Undergo WBRT

  • Radiosurgery (SRS)Radiation

    Also called Radiation surgery, SRS

    Undergo SRS

Study groups in NCT02145910
Study groupRoleWhat they receive
WBRT + VemurafenibExperimentalPatients undergo WBRT once daily (QD) for 10 doses
Receives: Drug: Vemurafenib; Radiation: Whole-brain radiation therapy (WBRT)
SRS + VemurafenibExperimentalPatients undergo SRS (gamma knife, tomotherapy, cyberknife, or megavoltage LINAC radiation therapy) on day 1
Receives: Drug: Vemurafenib; Radiation: Radiosurgery (SRS)

What is being measured

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

  1. Maximum tolerated dose (MTD) of vemurafenib

    The last dose studied or the previous dose, based on clinical judgment of the degree of toxicity seen at the last dose.

    Measured: Up to 1 year

Secondary outcomes (8)

  1. Proportion with complete response

    Estimate through the Kaplan-Meier method and compute associated 95% confidence intervals

    Measured: Up to 1 year

  2. Proportion with partial response

    Estimate through the Kaplan-Meier method and compute associated 95% confidence intervals

    Measured: Up to 1 year

  3. Median survival

    Estimate through the Kaplan-Meier method and compute associated 95% confidence intervals

    Measured: Up to 1 year

  4. Progression free survival based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria based on the brain MRI and systematic assessment by the treating physician

    Will be determined for each arm separately, as well as the entire study patient population

    Measured: Up to 1 year

  5. Overall survival

    Will be determined for each arm separately, as well as the entire study patient population

    Measured: Up to 1 year

  6. Local control rates of brain metastases

    Analysis of local control will be done separately in each arm

    Measured: Up to 1 year

  7. Rate of developing new brain metastasis

    Analysis of rate of developing new brain metastasis will be done separately in each arm

    Measured: Up to 1 year

  8. Response of extracranial disease

    Will be determined for each arm separately, as well as the entire study patient population

    Measured: Up to 1 year

Timeline

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

  1. First posted23 May 2014 (estimated)
  2. Primary completionJun 2019 (estimated)

Why it stopped: Study was never opened to accrual. There is no clinical benefit to patients.

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02145910
Sponsor's protocol ID
13P.480
Other IDs
2013-025, JT 2960
Status last verified
May 2025
First submitted
13 May 2014
Last updated
2 May 2025
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vemurafenib, Whole-brain radiation therapy (WBRT) and Radiosurgery (SRS) in people with Recurrent Melanoma and Stage IV Melanoma, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University.

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 35 inclusion and 11 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: withdrawn, as of the sponsor's last update on 2 May 2025. Status can change between updates, so confirm with the study contact before making plans.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Maximum tolerated dose (MTD) of vemurafenib (time frame: Up to 1 year). 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 NCT02145910.

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 2 May 2025.

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