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Metastatic Malignant Neoplasm in the BrainPhase 1NCT01904123

STAT3 Inhibitor WP1066 in Treating Patients With Recurrent Malignant Glioma or Progressive Metastatic Melanoma in the Brain

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and STAT3 Inhibitor WP1066 in people with Metastatic Malignant Neoplasm in the Brain and Metastatic Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.

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 phase I trial studies the side effects and best dose of STAT3 inhibitor WP1066 in treating patients with malignant glioma that has come back or melanoma that has spread to the brain and is growing, spreading, or getting worse. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pharmacological Study and STAT3 Inhibitor WP1066
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
13 Jul 2018to 16 Mar 2022
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

  • Patients must have histologically confirmed progressive brain metastases from melanoma or recurrent/progressive malignant glioma (glioblastoma, anaplastic glioma), for which standard curative or palliative measures, with the exception of surgery, do not exist or are no longer effective
  • Patients must have measurable disease in the brain, defined as at least one lesion that can be accurately measured in at least one dimension as >= 10 mm by brain magnetic resonance imaging (MRI); MRI of the brain (with and without gadolinium enhancement) is to be performed using standard 5-mm slices with 2.5-mm spacing for comparison to subsequent MRI scans
  • In the case of malignant glioma patients, they must have previously undergone standard-of-care treatment including surgery, radiation, and first line adjuvant chemotherapy prior to the experimental treatment (WP1066); in the case of melanoma patients with brain metastasis, they may have previously undergone a resection (with radiographic evidence of progression), have undergone gamma knife radiosurgery (with radiographic evidence of progression), or have been treated with other systemic therapies that failed
  • Karnofsky performance scale score >= 60%
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,000/mcL
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  • Platelets >= 75,000/mcL
  • Total bilirubin =< 1.6
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Prothrombin time (PT)/partial thromboplastin time (PTT) < 1.5 x normal institutional standard
  • Ability to understand and the willingness to sign a written informed consent document
  • Melanoma patients must be intolerant of, or have disease that has proven refractory to approved therapies such as BRAF or MEK inhibitors for BRAF-positive metastatic melanoma and/or checkpoint blockade with either anti-PD1 or anti-CTLA-4 for metastatic melanoma
  • Willing and able to tolerate brain MRI's with contrast
  • Patients with stable seizures (e.g., no seizures for >= 14 days and not requiring escalation or addition of anti-epileptic drugs for 14 days from starting treatment) will be eligible
  • Patients who are eligible for the surgical expansion cohort are identified by the clinical team who have made the independent decision that the patient would benefit from non-emergent palliative surgical resection (i.e. they are not a candidate for gamma knife or other type of standard therapy)

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; biological agents, immune modulators, and targeted therapeutic approaches require a 2-week washout window
  • Patients who are receiving any other investigational agents require a 4 week washout period; patients who have received cellular or gene therapy at any time are not eligible
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to WP1066
  • The enzymatic metabolism profile of WP1066 is unknown; patients who are receiving drugs that significantly interact with the cytochrome P450 (CYP450) enzyme(s) are ineligible; however, if they are switched to other medications with a 2-week washout window, they will be eligible; patients are also excluded if they have been exposed within 7 days of planned first study treatment day to medications that are predominantly cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), cytochrome P450, family 2, subfamily C, polypeptide 9 (2C9) or cytochrome P450, family 2, subfamily C, polypeptide 19 (2C19) substrates, strong inhibitors or inducers, and sensitive substrates of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) with narrow therapeutic range; patients requiring escalation of the corticosteroid dose will be excluded, but patients receiving a stable or decreasing dose for at least one week will be eligible
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • No single lesion can be larger than 3 cm in maximal diameter; there may not be midline shift exceeding 5 mm or hydrocephalus
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  • Pregnant women are excluded from this study because WP1066 could potentially be teratogenic or have abortifacient effects; breastfeeding should be discontinued if the mother is treated with WP0166; female subjects of childbearing potential should be willing to use 2 methods of birth control prior to study entry, during the study, and for 2 months after the last dose of the study drug or be surgically sterile; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of WP1066 administration
  • Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with WP1066
  • Patients who have received bevacizumab, Gliadel, or are on active therapy with Optune are not eligible
  • The potential for further hemorrhaging with the use of WP1066 is unknown; furthermore, because brain melanoma metastases commonly hemorrhage, toxicity may be inappropriately attributed to WP1066 in this setting; it will be at the principal investigator's (PIs) discretion to enroll a patient who has a small, asymptomatic brain hemorrhage, but patients who have had symptomatic hemorrhages will be excluded
  • Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs will be excluded
  • Because one of the secondary objectives is PFS based on radiographic volumetric analysis of the tumor, the presence of diffuse leptomeningeal disease will be an exclusion criterion for this study; this is secondary to the inadequacy of measuring the extent of the tumor burden within this setting and the very poor prognosis of these patients
  • The cardiac toxicities of WP1066 are unknown; thus, patients who have a corrected QT (QTc) interval > 450 ms at base line will be excluded; concomitant use of agents that prolong the QT interval will be avoided
  • Malignant glioma patients within 12 weeks of completion of radiation concurrent temozolomide will be excluded
  • Melanoma patients with large or symptomatic brain metastasis, and in whom neurosurgical removal is indicated will not be eligible for this trial

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I Trial of WP1066 in Patients With Recurrent Malignant Glioma and Brain Metastasis From Melanoma

This phase I trial studies the side effects and best dose of STAT3 inhibitor WP1066 in treating patients with malignant glioma that has come back or melanoma that has spread to the brain and is growing, spreading, or getting worse. STAT3 inhibitor WP1066 may stop the growth of tumor cells and modulate the immune system.

Read the detailed description

PRIMARY OBJECTIVES; I. Identify the maximum tolerated dose (MTD) of STAT3 inhibitor WP1066 (WP1066) in patients with recurrent malignant glioma (glioblastoma, anaplastic glioma), and melanoma patients with progressive brain metastasis.

II. Assess the safety and tolerability of WP1066 in patients with recurrent malignant glioma and melanoma patients with progressive brain metastasis using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) with special attention directed at determining whether any induced autoimmune reactions occur.

SECONDARY OBJECTIVES:

  1. Pharmacokinetic analysis of the in vivo bioavailability of WP1066. II. Assess overall response rate (ORR) in patients with recurrent malignant gliomas and progressive metastatic melanoma to the brain.

III. Assess immunological response in patients with recurrent malignant glioma and melanoma patients with progressive brain metastasis treated with WP1066.

IV. Assess time to radiographically assessed progression and/or response in patients treated with WP1066.

  1. Assess progression-free survival (PFS) and overall survival (OS) in patients treated with WP1066.

VI. Estimate the proportion of patients treated with WP1066 who develop additional melanoma metastatic lesions, including those in the central nervous system (CNS).

OUTLINE: This is a dose-escalation study.

Patients receive STAT3 inhibitor WP1066 orally (PO) twice daily (BID) on Monday, Wednesday, and Friday of weeks 1 and 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 and 2 months.

Being tested
Laboratory Biomarker Analysis, Pharmacological Study, STAT3 Inhibitor WP1066
Medical subject headings
Brain Neoplasms, Melanoma, Glioblastoma, Glioma

What participants receive

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • STAT3 Inhibitor WP1066Drug

    Also called WP1066

    Given PO

Study groups in NCT01904123
Study groupRoleWhat they receive
Treatment (STAT3 inhibitor WP1066)ExperimentalPatients receive STAT3 inhibitor WP1066 PO BID on Monday, Wednesday, and Friday of weeks 1 and 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: STAT3 Inhibitor WP1066

What is being measured

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

  1. Maximum tolerated dose (MTD) of JAK2 inhibitor WP1066, defined as the dose level at which 0/6 or 1/6 patients experience a dose limiting toxicity (DLT) with at least 2 patients experiencing DLT at the next higher dose level

    A DLT will be defined as an adverse event or an abnormal laboratory value assessed as being at least possibly related to the investigation agent that occurs during the first 28 days after administration of the first dose of JAK2 inhibitor WP1066 and will be assigned a grade based on National Cancer Institute (NCI) Common Terminology Criteria (CTC). Any grade toxicity at least possibly related to WP1066 that leads to dose delay of >= 2 weeks will be considered a DLT.

    Measured: 28 days

  2. Incidence of adverse events assessed using NCI CTC

    Measured: Up to 2 months after the last study drug dose

Secondary outcomes (8)

  1. Pharmacokinetic analysis of the in vivo bioavailability of JAK2 inhibitor WP1066

    Measured: Days 1, 2, 14, and 15 of course 1

  2. Proportion of patients reaching complete response or partial response

    Estimated with a 95% confidence interval.

    Measured: Up to 2 months after the last study drug dose

  3. Duration of response

    Estimated using Kaplan-Meier survival curves. Cox proportional hazards regression methodology may be used to assess the association between duration of response or survival and clinical and demographic characteristics of interest.

    Measured: Up to 2 months after the last study drug dose

  4. Overall survival

    Estimated using Kaplan-Meier survival curves. Cox proportional hazards regression methodology may be used to assess the association between duration of response or survival and clinical and demographic characteristics of interest.

    Measured: Up to 2 months after the last study drug dose

  5. Progression free survival

    Estimated using Kaplan-Meier survival curves. Cox proportional hazards regression methodology may be used to assess the association between duration of response or survival and clinical and demographic characteristics of interest.

    Measured: Up to 2 months after the last study drug dose

  6. The proportion of patients who develop additional melanoma metastatic lesions

    Estimated with a 95% confidence interval.

    Measured: Up to 2 months after the last study drug dose

  7. Change in regulatory T cell numbers

    Tested using paired t-tests or Wilcoxon signed-rank tests, as appropriate. The longitudinal analysis for all markers will be similar using generalized linear mixed-effects (GLMM) models to assess the significance of the changing values over time and estimating the trajectory.

    Measured: Baseline up to 2 months after the last study drug dose

  8. Change in the number of peripheral blood mononuclear cells expressing phosphorylated STAT3

    Tested using paired t-tests or Wilcoxon signed-rank tests, as appropriate. The longitudinal analysis for all markers will be similar using GLMM models to assess the significance of the changing values over time and estimating the trajectory.

    Measured: Baseline up to 2 months after the last study drug dose

Timeline

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

  1. First posted22 Jul 2013 (estimated)
  2. Study start13 Jul 2018
  3. Primary completion16 Mar 2022
  4. Study completion16 Mar 2022

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01904123
Sponsor's protocol ID
2012-0358
Other IDs
NCI-2015-00163, 2012-0358, P50CA127001, P50CA093459
Status last verified
Mar 2022
First submitted
17 Jul 2013
Last updated
23 Mar 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Choi HK, Park SH, Lee J, Hwang JT. Review of Patents for Anticancer Agents Targeting Adenosine Monophosphate-Activated Protein Kinase. J Med Food. 2023 Sep;26(9):605-615. doi: 10.1089/jmf.2023.K.0026. Epub 2023 Aug 16.

    PubMed 37590001

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and STAT3 Inhibitor WP1066 in people with Metastatic Malignant Neoplasm in the Brain and Metastatic Melanoma, run by M.D. Anderson Cancer Center 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 16 inclusion and 15 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 23 Mar 2022. 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 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 JAK2 inhibitor WP1066, defined as the dose level at which 0/6 or 1/6 patients experience a dose limiting toxicity (DLT) with at least 2 patients experiencing DLT at the next higher dose level (time frame: 28 days). The study lists 2 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 NCT01904123, which also lists 1 linked publication.

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 23 Mar 2022.

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