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Colorectal AdenocarcinomaPhase 1NCT02650635

TLR8 Agonist VTX-2337 and Cyclophosphamide in Treating Patients With Metastatic, Persistent, Recurrent, or Progressive Solid Tumors

A Phase 1 study testing Cyclophosphamide, Laboratory Biomarker Analysis and Pegfilgrastim in people with Colorectal Adenocarcinoma and Metastatic Pancreatic Adenocarcinoma, run by Mayo Clinic at 1 site 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 Ib trial studies the best way of TLR8 Agonist VTX-2337 and cyclophosphamide in treating patients with a solid tumor that has spread from the primary site (place where it started) to other places in the body (metastatic), progressed for a long time (persistent), come back (recurrent), or is growing… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Laboratory Biomarker Analysis and Pegfilgrastim
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
5 Feb 2016to 1 Jun 2017
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

  • Histologically or cytologically confirmed metastatic solid tumor, including but not limited to pancreatic adenocarcinoma, breast cancer, melanoma, renal cell carcinoma (RCC), colorectal adenocarcinoma, non-small cell lung cancer, and others approved by the principal investigator
  • Persistent, recurrent or progressive disease following at least one prior line of systemic therapy and there is no available therapy likely to improve survival
  • Measurable disease with >= 1 target lesion
  • White blood cells (WBC) >= 4200/mm^3
  • Absolute neutrophil count (ANC) >= 1400/mm^3
  • Platelets (PLT) >= 100,000/mm^3
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  • Lymphocytes >= 700/mm^3
  • Hemoglobin >= 10 g/dL
  • Total bilirubin =< 1.5 X upper limit of normal (ULN) unless history of Gilbert's syndrome documented prior to first-line treatment of cancer and other liver function tests are within normal limits
  • Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.2 x ULN unless on anticoagulation medication with stable dosing for at least one month; in addition, patient must be able to stop taking medication for up to a week in order to have percutaneous biopsies of tumor tissue performed
  • Aspartate transaminase (AST) and alanine aminotransferase (ALT) =< 1.5 x ULN (=< 5 x ULN for patients with liver involvement)
  • Creatinine =< ULN or a calculated creatinine clearance of >= 45 ml/min if creatinine is greater than the ULN
  • Alkaline phosphatase =< 3 x ULN (=< 5 x ULN if liver or bone involvement)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • Willing and able to provide informed written consent
  • Willing and able 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 and observation), participants must be willing and able to return to the consenting institution for follow-up
  • Estimated life expectancy >= 84 days (3 months)
  • Willing and able to provide samples for correlative research purposes
  • If female of child-bearing potential, have a negative pregnancy test =< 14 days prior to registration
  • If fertile male or female of child-bearing potential, agree to consistently use a highly effective method of birth control (including birth control pills, barrier device, or intrauterine device) from the time of consent through 4 months following the last dose of study drug

Who cannot join

  • Is pregnant, breastfeeding, or planning a pregnancy
  • Known standard therapy for the patient's disease that is potentially curative
  • Treatment with any systemic anticancer treatment or an investigational agent within 4 weeks and any radiation within 2 weeks of registration
  • 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 subject safety or compliance with study requirements
  • Active autoimmune disease, defined as any autoimmune condition currently requiring therapy (e.g., systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis)
  • History of other invasive malignancy, with the exception of non-melanoma skin cancer and well-excised cervical carcinoma in situ, =< 3 years prior to enrollment unless assessed by the principal investigator as unlikely to compromise subject safety or to interfere with the study's objectives
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  • Treatment with oral or parenteral corticosteroids dosed greater than 40 mg hydrocortisone daily or its equivalent (e.g., prednisone 10 mg, prednisolone 8 mg, or decadron 3 mg) =< 2 weeks of treatment initiation; or a clinical requirement for ongoing systemic immunosuppressive therapy
  • History of central nervous system (CNS) metastases unless previously treated and stable for > 8 weeks prior to study initiation
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive
  • Hypersensitivity to pegfilgrastim or Escherichia (E.) coli derived proteins

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: Phase IB Study Investigating the Tolerability, Immunomodulatory Impacts and, Therapeutic Correlates of the Novel Toll-like Receptor 8 Agonist Motolimod (MOTO) Plus Cyclophosphamide (CTX) Treatment of Advanced Solid Tumors

This phase Ib trial studies the best way of TLR8 Agonist VTX-2337 and cyclophosphamide in treating patients with a solid tumor that has spread from the primary site (place where it started) to other places in the body (metastatic), progressed for a long time (persistent), come back (recurrent), or is growing, spreading, or getting worse (progressed). TLR8 Agonist VTX-2337 may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving TLR8 Agonist VTX-2337 together with cyclophosphamide may be a better treatment for solid tumors.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the ability of a dosing schedule of cyclophosphamide, pegfilgrastim, and TLR8 agonist VTX-2337 (CyNeuMoto) to reproducibly immunomodulate patients in a manner which enhances the endogenous antitumor effector response.

SECONDARY OBJECTIVES:

  1. To assess the safety and tolerability of this treatment by assessing the adverse events.

II. Best overall response rate, as assessed by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria (irBORR).

III. Duration of tumor response, as assessed by irRECIST (irDOR). IV. Progression-free survival (PFS) as measured by serial imaging studies and assessed by irRECIST.

  1. Overall survival, as measured by subject vital status for 36 months following discontinuation of study treatment.

TERTIARY OBJECTIVES:

  1. To test the hypothesis that this regimen will prove efficacious as an immunomodulator regardless of the number of prior chemotherapy (chemo) regimens or type of cancer assessed.

II. To evaluate baseline immune status in patients (peripheral blood and intratumoral effector T cells, regulatory T cells, tumoricidal monocytes, and myeloid-derived suppressor cells) as well as the modulatory effects of the treatment upon individual immune components.

III. To correlate treatment-induced immune modulations to clinical outcomes (overall response rate [ORR], progression-free survival [PFS] as determined by immune-related RECIST [irRECIST], and overall survival).

IV. To correlate treatment-induced immune modulations and clinical outcomes to the magnitude of leukopenia (and its surrogate, neutropenia) achieved by the treatment.

OUTLINE:

Patients receive cyclophosphamide intravenously (IV) over 30 minutes on day 1, pegfilgrastim subcutaneously (SC) on day 2, and TLR8 agonist VTX-2337 SC on day -6 of course 1 only and on days 9 and 16. Patients achieving complete response (CR), partial response (PR), or stable disease (SD) may continue therapy every 21 days for 3 additional courses. Treatment may then continue in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 36 months.

Being tested
Cyclophosphamide, Laboratory Biomarker Analysis, Pegfilgrastim, Pharmacological Study, TLR8 Agonist VTX-2337
Medical subject headings
Breast Neoplasms, Colorectal Neoplasms, Melanoma, Carcinoma, Non-Small-Cell Lung, Pancreatic Neoplasms, Carcinoma, Renal Cell

What participants receive

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

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PegfilgrastimBiological

    Also called Filgrastim SD-01, filgrastim-SD/01, HSP-130, Neulasta

    Given SC

  • Pharmacological StudyOther

    Correlative studies

  • TLR8 Agonist VTX-2337Drug

    Also called Toll-like Receptor 8 Agonist VTX-2337, VTX-2337

    Given SC

Study groups in NCT02650635
Study groupRoleWhat they receive
Treatment (CTX, pegfilgrastim, TLR8 agonist VTX-2337)ExperimentalPatients receive cyclophosphamide IV over 30 minutes on day 1, pegfilgrastim SC on day 2, and TLR8 agonist VTX-2337 SC on day -6 of course 1 only and on days 9 and 16. Patients achieving CR, PR, or SD may continue therapy every 21 days for 3 additional courses. Treatment may then continue in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Biological: Pegfilgrastim; Other: Pharmacological Study; Drug: TLR8 Agonist VTX-2337

What is being measured

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

  1. Change in pharmacodynamics after TLR8 agonist VTX-2337 alone vs TLR8 agonist VTX-2337+cyclophosphamide

    The pharmacodynamics after TLR8 agonist VTX-2337 alone will be compared to TLR8 agonist VTX-2337+cyclophosphamide to test the hypothesis that TLR8 agonist VTX-2337+cyclophosphamide (course 2) will be significantly more immunomodulatory than TLR8 agonist VTX-2337 alone (course 1 run in dose) in regards to (1) reducing % and absolute numbers of Tregs compared to total lymphocytes; (2) reducing absolute numbers of MDSCs; (3) increasing % of total peripheral T cells activatable to produce IFNg; and (4) increasing % of total peripheral monocytes activatable to produce nitric oxide or express induci

    Measured: Up to end of course 2 (42 days)

Secondary outcomes (5)

  1. Duration of response, assessed by irDOR, defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented

    The distribution of duration of response will be estimated using the method of Kaplan-Meier. Supplemental statistical analysis will include comparison of the duration of response between groups of interest using a Cox proportional hazards model. As an exploratory analysis, will also determine if patients who achieve sustained intratreatment responses (defined as disease stabilization or a maximum objective response unchanged over six cycles of treatment) continue to maintain this response upon cessation of treatment.

    Measured: Up to 36 months

  2. Incidence of adverse events of cyclophosphamide and TLR8 agonist VTX-2337, using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns using CTCAE version 4.0.

    Measured: Up to 36 months

  3. Overall response rate assessed by irBORR

    Measured: Up to 36 months

  4. Overall survival (OS)

    The distributions of OS will be estimated using Kaplan-Meier methodology and will be compared between groups of interest using a log-rank test. Supplemental statistical analysis will include comparison of the OS between groups of interest using a Cox proportional hazards model.

    Measured: Time from study entry to death due to any cause, assessed up to 36 months

  5. PFS as measured by serial imaging studies and assessed by irRECIST

    The distribution of PFS will be estimated using Kaplan-Meier methodology. Supplemental statistical analysis will include comparison of the PFS between groups of interest using a Cox proportional hazards model.

    Measured: Time from study entry to the first of either progression or death due to any cause, assessed up to 36 months

Timeline

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

  1. First posted8 Jan 2016 (estimated)
  2. Study start5 Feb 2016
  3. Primary completion26 Sep 2016
  4. Study completion1 Jun 2017

Why it stopped: permanently closed per sponsor's request

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
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02650635
Sponsor's protocol ID
MC1245
Other IDs
NCI-2015-02150, MC1245, P30CA015083
Status last verified
Aug 2018
First submitted
30 Dec 2015
Last updated
5 Sep 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Laboratory Biomarker Analysis and Pegfilgrastim in people with Colorectal Adenocarcinoma and Metastatic Pancreatic Adenocarcinoma, run by Mayo Clinic 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 20 inclusion and 10 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 5 Sep 2018. 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 was stopped early (reason given: permanently closed per sponsor's request). Results are not available in the source record.

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?

Change in pharmacodynamics after TLR8 agonist VTX-2337 alone vs TLR8 agonist VTX-2337+cyclophosphamide (time frame: Up to end of course 2 (42 days)). 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 NCT02650635.

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 5 Sep 2018.

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