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Anatomic Stage 0 Breast Cancer AJCC v8Phase 1NCT04081389

Chemokine Modulation Therapy and Standard Chemotherapy Before Surgery for the Treatment of Early Stage Triple Negative Breast Cancer

A Phase 1 study testing Celecoxib, Cyclophosphamide and Doxorubicin in people with Anatomic Stage 0 Breast Cancer AJCC v8 and Anatomic Stage I Breast Cancer AJCC v8, run by Roswell Park Cancer Institute 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 how well chemokine modulation therapy and standard chemotherapy given before surgery work in treating patients with early stage triple negative breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Celecoxib, Cyclophosphamide and Doxorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
6 Dec 2019to 27 Feb 2023
Phase
Phase 1
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

  • Have pathologically confirmed diagnosis of resectable triple negative breast cancer (ASCO/CAP guidelines will be used to define triple negative breast cancer)
  • Must have measurable disease. Multi-centric disease is allowed. If patient has another lesion which is biopsied with ER/PR positive it will be Physician discretion for this eligibility criteria.
  • Prior therapy: No prior cytotoxic regimens are allowed for this malignancy. Participants may not have had prior chemotherapy, other targeted anticancer therapies, or prior radiation therapy to the ipsilateral breast for this malignancy. Prior bis-phosphonate therapy is allowed
  • Patient eligible for surgery as determined by patient's surgeon
  • Patient must have a lesion that amendable to biopsy, unless inaccessible and with PI approval
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
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  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. 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
  • Ability to swallow and retain oral medication
  • Ability to undergo magnetic resonance imaging (MRI)
  • Platelets >= 100,000/uL
  • Hemoglobin >= 9 g/dL
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Total bilirubin =< institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and ALT (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 X institutional upper limit of normal (ULN)
  • Creatinine < ULN OR creatinine clearance >= 50 mL/min per Cockcroft-Gault equation for patients with creatinine levels greater than ULN
  • Left ventricular ejection fraction (LVEF) >= 55%; if LVEF is < 55% and patient is otherwise study-eligible, the principal investigator (PI) will discuss with cardiologist if patient is eligible to receive doxorubicin and participate in study
  • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
  • Participants on this study will be counseled on and are willing to use adequate contraceptive methods

Who cannot join

  • Patients currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment
  • Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation
  • Diagnosis of invasive carcinoma within the last 3 years
  • Inflammatory breast cancer will be excluded from the study
  • Participants who have metallic surgical implants that are not compatible with an MRI machine are not eligible
  • Pregnant or nursing female participants
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  • Unwilling or unable to follow protocol requirements
  • Patients with known serious mood disorders. (Major depression is an exclusion. Other stable mood disorders on stable therapy for > 6 months may be allowed after consultation with PI)
  • Cardiac risk factors including:
  • Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent
  • Patients with a New York Heart Association classification of III or IV
  • History of upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years
  • Prior allergic reaction or hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) or any drugs administered on protocol
  • Any history of allergy to sulfonamides
  • Any history of autoimmune hepatitis
  • Grade 1 or higher neuropathy
  • Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: Phase I Clinical Trial Assessing the Combination of Chemokine Modulation With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer

This phase I trial studies how well chemokine modulation therapy and standard chemotherapy given before surgery work in treating patients with early stage triple negative breast cancer. Chemokine modulation therapy, including celecoxib, recombinant interferon alfa-2b, and rintatolimod, may stimulate the immune system and stop tumor cells from growing. Drugs used in standard chemotherapy, such as paclitaxel, doxorubicin, and 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 chemokine modulation therapy together with standard chemotherapy may work better than giving either therapy alone in treating patients with triple negative breast cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To examine the safety and tolerability profile of the combination of rintatolimod celecoxib +/- interferon alpha-2b, when given as CKM along with chemotherapy in the neoadjuvant setting in early stage triple negative breast cancer.

II To identify the appropriate dose level of CKM and paclitaxel for future clinical exploration.

SECONDARY OBJECTIVES:

II. • Evaluate the effect of neoadjuvant CKM + paclitaxel on pathological response and breast MRI response in early stage triple negative breast cancer patients.

III. • Evaluate the overall and recurrence-free survival in early stage triple negative breast cancer patients that received neoadjuvant CKM + paclitaxel.

EXPLORATORY OBJECTIVES:

I• To evaluate longitudinal changes of blood biomarkers such as peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), expression of chemokine and other immune genes, circulating immune mediators and correlate them with the clinical course post surgery.

II• Comparison of response assessment criteria for a prospective analysis using RECIST 1.1. and irRECIST

  • Evaluate changes in the intratumoral levels of biomarkers, such as, peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), chemokines, and immune-regulatory factors (pre- vs post-CKM + paclitaxel treatment).

OUTLINE: This is a phase Ib, dose-escalation study of recombinant interferon alfa-2b.

Patients receive celecoxib orally (PO) twice daily (BID), recombinant interferon alfa-2b intravenously (IV) over 20 minutes (omitted in lowest dose level), and rintatolimod IV on days 1-3 of weeks 1-3, as well as paclitaxel IV over 1 hour once weekly on day 1. Treatment continues for a total of 12 weeks in the absence of disease progression or unacceptable toxicity. 1-3 weeks after last dose of paclitaxel, patients receive doxorubicin IV over 10 minutes and cyclophosphamide IV over 30 minutes. Treatment repeats every 2 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity.

. After completion of study treatment, patients are followed up at 2 weeks.

Medical subject headings
Breast Carcinoma In Situ, Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

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

  • CelecoxibDrug

    Also called Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177

    Given PO

  • CyclophosphamideDrug

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

    Given IV

  • DoxorubicinDrug

    Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin

    Given IV

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Recombinant Interferon Alfa-2bBiological

    Also called Alfatronol, Glucoferon, Heberon Alfa, IFN alpha-2B

    Given IV

  • RintatolimodDrug

    Also called Ampligen, Atvogen

    Given IV

Study groups in NCT04081389
Study groupRoleWhat they receive
CKM weeks 1-3, doxorubicin, cyclophosphamide)ExperimentalPatients receive celecoxib PO BID, recombinant interferon alfa-2b IV over 20 minutes, and rintatolimod IV on days 1-3 of weeks 1-3, as well as paclitaxel IV over 1 hour once weekly on day 1. Treatment continues for a total of 12 weeks in the absence of disease progression or unacceptable toxicity. 1-3 weeks after last dose of paclitaxel, patients receive doxorubicin IV over 10 minutes and cyclophosphamide IV over 30 minutes. Treatment repeats every 2 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Celecoxib; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Doxorubicin Hydrochloride; Drug: Paclitaxel; Biological: Recombinant Interferon Alfa-2b; Drug: Rintatolimod

What is being measured

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

  1. Number of Patients With Dose Limiting Toxicities

    Safety and toxicity will be assessed using the CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE Version 5.0). The resulting dose limiting toxicity (DLT) information is used to identify the appropriate dose level of CKM and paclitaxel for future clinical exploration.

    The following events will be considered a DLT:

    • The event occurs within 3 weeks following 1st dose of combination CKM + paclitaxel therapy and subsequent enrollment for dose-escalation will only proceed after the 3-week period has been completed.
    • The toxicity has been determined by the investigator to be possibly, probably or definitely related to celecoxib, rintatolimod, interferon-α2b or paclitaxel.
    • Any death not clearly due to th

    Measured: Within 21 days of treatment adminstration

Secondary outcomes (4)

  1. Number of Patients With Pathological Complete Response (pCR)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI, where Complete Response (CR) corresponds to the disappearance of all target lesions.

    Measured: Up to 4 week post-treatment (with a range of 7 to 11 weeks).

  2. Residual Cancer Burden Index

    The calculated RCB index value is categorized as one of four RCB classes, RCB-0 to RCB-III where RCB-0 is best prognosis (no residual disease) to RCB-III a worst prognosis.

    Measured: At 12 weeks post treatment initiation.

  3. Recurrence-free Survival (RFS)

    RFS is defined as local/regional invasive recurrence, invasive ipsilateral breast tumor recurrence, distant recurrence, inoperable (meaning no surgery because of progression), and/or death from breast cancer (per standard of care according to physician discretion) or any cause. RFS will be calculated from the time of treatment to event. The median RFS was estimated using standard Kaplan-Meier methods (where NR = not reached).

    Measured: At 3 years

  4. Overall Survival (OS)

    OS is defined by death from breast cancer, non-breast cancer, unknown, or any other cause and will be calculated from the time of study entry to event. The median OS is estimated using standard Kaplan-Meier methods (where NR = not reached).

    Measured: At 3 years

Timeline

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

  1. First posted9 Sep 2019
  2. Study start6 Dec 2019
  3. Primary completion24 May 2022
  4. Study completion27 Feb 2023

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
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04081389
Sponsor's protocol ID
I 73718
Other IDs
NCI-2019-05299, I 73718, UL1TR001412
Status last verified
Aug 2023
First submitted
27 Aug 2019
Last updated
11 Sep 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Celecoxib, Cyclophosphamide and Doxorubicin in people with Anatomic Stage 0 Breast Cancer AJCC v8 and Anatomic Stage I Breast Cancer AJCC v8, run by Roswell Park Cancer Institute 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 18 inclusion and 17 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 11 Sep 2023. 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?

Yes. Results are posted in the registry (first posted 11 Sep 2023). 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?

Number of Patients With Dose Limiting Toxicities (time frame: Within 21 days of treatment adminstration). 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 NCT04081389.

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 11 Sep 2023.

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