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Breast CancerPhase 1NCT02824575

Rebastinib Plus Antitubulin Therapy With Paclitaxel or Eribulin in Metastatic Breast Cancer

A Phase 1 study testing Rebastinib, Paclitaxel and Eribulin Mesylate in people with Breast Cancer and Breast Adenocarcinoma, run by Montefiore Medical Center 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

The purpose of this study is to determine the safety and tolerability of rebastinib when combined with antitubulin therapy with paclitaxel or eribulin in patients with advanced breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Rebastinib, Paclitaxel and Eribulin Mesylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
Jul 2016to 27 Dec 2021
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed adenocarcinoma of the breast that is HER2 (human epidermal growth factor receptor 2) negative; based on ASCO(american society of clinical oncology)/ CAP (college of American Pathologists) guidelines as: (a) IHC (immuno-histochemistry) 1+ negative or IHC 0 negative; or (b) ISH (in situ hybridization ) negative using single probe ISH( average HER2 copy number < 4.0 signals/cell), or dual probe ISH ( HER2/CEP17 ratio <2.0, average HER2 copy number <4.0 signals/cell)
  • Metastatic breast cancer not amenable to potentially curative surgery. Patients must have disease that is measurable and/or non-measurable as defined by RECIST 1.1 criteria
  • Prior chemotherapy and/or endocrine therapy. Patients will be assigned to arm A or arm B depending on their prior exposure to paclitaxel and eribulin.
  • Arm A: Rebastinib plus paclitaxel: Up to two prior non-taxane chemotherapy regimens for metastatic or incurable locally advanced disease permitted (no prior paclitaxel, docetaxel, or eribulin for metastatic disease)..Prior therapy with paclitaxel or docetaxel in the neo/adjuvant setting is allowable if there is at least a 6 month interval between the last adjuvant/neoadjuvant paclitaxel or docetaxel dose and recurrence.
  • Arm B: Rebastinib plus Eribulin: Patients must have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease (no prior eribulin, but prior paclitaxel, nab-paclitaxel, or docetaxel allowed). Prior therapy should have included a taxane in either the adjuvant or metastatic setting.
  • Arms A and B: Patients with hormone receptor positive disease must have had progressive disease and at least 2 lines of endocrine therapy, including one endocrine regimen used in combination with an approved CDK 4/6 (cyclin-dependent kinase ) inhibitor (eg, palbociclib). Relapse while receiving or within 6 months of completing adjuvant endocrine therapy may be considered failure of one prior endocrine regimen
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  • Female and age >18 years. Because breast carcinoma is a disease of adults that rarely occurs in children, children are excluded from this study. In addition, the safety of rebastinib in pediatric patients has not been evaluated.
  • ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1.
  • Normal organ and marrow function as defined below within 2 weeks of registration (except where specified otherwise):
  • Leukocytes >3,000/µL ; Absolute neutrophil count >1,500/µL ; Platelets >100,000/ µL Hemoglobin > 9 g/dL ; Total bilirubin (within normal institutional limits) AST (aspartate aminotransferase)/ALT (alanine aminotransferase) <2.5 X institutional upper limit of normal ; Creatinine (within normal institutional limits) ; EKG QTc < 450 msec (females)
  • Left ventricular ejection fraction at or above institutional lower limits of normal (by echocardiogram within 12 weeks of registration) ; Glucose (within normal limits) Serum calcium \& phosphorus (within normal institutional limits); Negative urine or serum B-HCG(Beta-Human Chorionic Gonadotropin)
  • No significant ocular disease: No prior known history of retinal neovascularization, macular edema or macular degeneration. Patients without such a history are required to have a baseline ophthalmologic exam as part of screening, and must not have evidence of retinal neovascularization, macular edema or macular degeneration on the screening exam in order to be eligible.
  • No other active cancer: Patients must be disease-free of prior invasive malignancies for > 2 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix. Patient with the following prior or concurrent diagnoses are eligible: lobular carcinoma in situ, contralateral ductal carcinoma in situ, or contralateral invasive ductal and/or lobular carcinoma.
  • Women of child-bearing potential must not be pregnant or breast feeding. They must also agree to use adequate contraception (hormonal or barrier method of birth control) and not be breast feeding prior to study entry, for the duration of study participation, and for up to 30 days after completion of all protocol therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study or up to 30 days after completion of protocol therapy, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.
  • At least 30 days from major surgery before study enrollment, with full recovery.
  • Concomitant therapy with bisphosphonates, RANKL inhibitors or growth-colony-stimulating factor (G-CSF) is allowed as per physician decision.
  • Expansion cohort: Patients for the expansion cohort must have a CTC (TelomeScan) drawn in the screening phase if other eligibility criteria are met, and must be CTC-positive in order to be eligible for enrollment in the expansion cohort.

Who cannot join

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Rebastinib or other agents used in the study (e.g., Cremophor)
  • History of cardiac disease, including: (a) myocardial infarction within 6 months of the start of study, (b) history of QTc(corrected QT interval ) prolongation or QTc >/= 450 msec on screening EKG, history of additional risk factors for Torsade de pointes( e.g., heart failure, hyperkalemia, and family history of long QT syndrome. (c) Use of concomitant drugs that prolong QT/QTc interval.(see "Study reference manual" for further details) (d) New York Heart Association class III or IV heart disease, (e), active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy.
  • bIntercurrent illness that would substantially increase the risk of treatment associated complications (e.g., active infection, uncontrolled diabetes mellitus or hypertension) and/or psychiatric illness/social situations that would interfere with the patient's ability to comply with the treatment regimen.
  • Patients with HIV infection are excluded from the study because of possible pharmacokinetic interactions with Rebastinib and antiretroviral therapy.
  • Patients with untreated brain metastasis are excluded. Patients with a prior history of brain metastasis are eligible if they have received prior brain radiation, have improved or stable intracranial disease for at least 3 months after completion of last course of radiation, and are not taking corticosteroids for treatment of brain metastasis. Patients with a prior history of brain metastases who meet other eligibility criteria
  • Treatment with other chemotherapy regimen within the past 2 weeks.
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  • Treatment with trastuzumab, bevacizumab or other targeted therapies within the past 4 weeks.
  • Patients who have not recovered (i.e., CTCAE Grade ≤1 or baseline) from an adverse event due to a previously administered agent, excluding alopecia.
  • Patients with Grade >1 neuropathy
  • Patients with uncontrolled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 90 mm/mg).
  • Patients that have a malabsorption syndrome or other illness which could affect oral absorption

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Montefiore Medical Center

    The Bronx, New York, 10461

Other trials in United States

About this study

Official title: Phase Ib Study of Rebastinib Plus Antitubulin Therapy With Paclitaxel or Eribulin in Patients With Metastatic Breast Cancer

The purpose of this study is to determine the safety and tolerability of rebastinib when combined with antitubulin therapy with paclitaxel or eribulin in patients with advanced breast cancer.

Read the detailed description

Metastasis is the primary cause of death from breast cancer, invasive carcinoma cells in mouse and rat mammary tumors co-migrate accompanied by macrophages towards intravasation sites . The intravasation occurs at sites where a TIE2-expressing macrophage, a mena-expressing tumor cell, and an endothelial cell are in direct contact, forming a micro-anatomic structure called tumor micro-environment of metastasis (TMEM). Ablation of the presence or activity of the TMEM associated macrophages blocks intravasation at TMEM demonstrating an essential role of perivascular macrophages in TMEM function. Rebastinib, a TIE2 inhibitor , blocks TMEM assembly and function in-vivo and in-vitro assays. We hypothesize that rebastinib combined with antitubulin therapy (eribulin or paclitaxel) could improve clinical outcomes in breast cancer by preventing intravasation at TMEM sites and preventing further metastasis.

Being tested
Rebastinib, Paclitaxel, Eribulin Mesylate
Keywords
breast cancer, chemotherapy, metastasis, tumor micro-environment
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

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

  • RebastinibDrug

    Also called DCC-2036

    50 mg or 100 mg po BID continuously. Cycle duration: 21 days. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

  • PaclitaxelDrug

    Also called Taxol

    Paclitaxel 80 mg/m2 weekly. Cycle duration = 21 days. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

  • Eribulin MesylateDrug

    Also called Halaven

    Eribulin 1.4 mg/m2 day 1 \& 8. Cycle duration : 21 days. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

Study groups in NCT02824575
Study groupRoleWhat they receive
Arm A1-2: Paclitaxel plus Rebastinib.Experimental* Arm A1 (Dose Escalation Cohort): Paclitaxel 80 mg/m2 weekly x 12 weeks plus Rebastinib (50 mg PO BID or 100 mg PO BID) beginning on cycle 1, day 1 and given continuously. * Arm A2 (Expansion Cohort): Paclitaxel 80 mg/m2 weekly x 12 weeks. Patients will be randomized to receive Rebastinib (at RP2D) beginning on cycle 1, day 1 OR cycle 2, day 1.
Receives: Drug: Rebastinib; Drug: Paclitaxel
Arm B1-2: Eribulin plus Rebastinib.Experimental* Arm B1 (Dose Escalation Cohort): Eribulin Mesylate 1.4 mg/m2 day 1 \& 8 q21 days plus Rebastinib (50 mg PO BID or 100 mg PO BID) beginning on cycle 1, day 1 and given continuously. * Arm B2 (Expansion Cohort): Eribulin Mesylate 1.4 mg/m2 day 1 \& 8 q21 days. Patients will be randomized to receive Rebastinib (at RP2D) beginning on cycle 1, day 1 OR cycle 2, day 1.
Receives: Drug: Rebastinib; Drug: Eribulin Mesylate

What is being measured

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

  1. Recommended Phase 2 dose(RP2D).

    Arm A: To determine the recommended phase II dose (Arm A1 - dose escalation cohort) and overall safety profile (Arm A2 - expansion cohort) of Rebastinib (50 mg PO BID or 100 mg PO BID) given concurrently with weekly paclitaxel (80 mg/m2 weekly x 12 ) over 3 consecutive weeks (1 cycle) in patients with metastatic breast cancer.

    Arm B: To determine the recommended phase II dose (Arm B1 - dose escalation cohort) and overall safety profile (Arm B2 - expansion cohort) of Rebastinib (50 mg PO BID or 100 mg PO BID) given concurrently with weekly eribulin (1.4 mg/m2 days 1 and 8 every 21 days) over 3 consecutive weeks (1 cycle) in patients with metastatic breast cancer.

    Measured: After 1 treatment cycle (3 weeks) during dose escalation cohort (N=24)

Secondary outcomes (7)

  1. Median Progression Free Survival (PFS)

    Arm A1-2 and Arm B1-2 (evaluate separately for each arm): To determine the progression-free survival of patients treated with Rebastinib plus paclitaxel, and Rebastinib plus eribulin (at all Rebastinib dose levels).

    Measured: From treatment start until progression or death, whichever occurs first, assessed up to 36 months

  2. Median Overall Survival (OS).

    Arm A1-2 and Arm B1-2 (evaluate separately for each arm): To determine overall survival of patients treated with Rebastinib plus paclitaxel, and Rebastinib plus eribulin (at all Rebastinib dose levels).

    Measured: From treatment start until death by any cause, assessed up to 36 months.

  3. Clinical benefit rate

    Arm A1-2 and Arm B1-2 (evaluate separately for each arm): To determine clinical benefit rate of patients treated with Rebastinib plus paclitaxel, and Rebastinib plus eribulin (at all Rebastinib dose levels).

    Measured: Proportion of patients who achieved complete response or partial response for at least 24 weeks after study start.

  4. Change of ANG1 and ANG2 levels

    Arm A1-2 plus Arm B1-2 (evaluate combined dataset including both arms): To determine correlation between Rebastinib and angiopoietin (ANG1 and/or ANG2) levels (a surrogate marker for TIE2 inhibition)

    Measured: Before and after cycle 1( week 3) for each patient.

  5. Change in Circulating Tumor Cells (CTC) levels.

    Arm A2 plus Arm B2: To perform an exploratory analysis of the effects of Rebastinib plus antitubulin therapy on circulating tumor cell (CTCs) during cycle 1, by comparing CTCs during cycle 1 in patients randomized to receive or not rebastinib during cycle 1.

    Measured: Before and after cycle 1( week 3) for each patient.

  6. Change in TIE-2 expressing monocyte levels.

    Arm A2 plus Arm B2: To perform an exploratory analysis of the effects of Rebastinib plus antitubulin therapy on TIE-2 expressing monocytes (TEM) during cycle 1.

    Measured: Before and after cycle 1( week 3) for each patient.

  7. Change in TMEM score.

    Arm A2 or Arm B2: To perform an exploratory analysis of the effects of Rebastinib plus antitubulin therapy on TMEM score and TMEM function in a cohort of up to 6 patients with metastatic cancer who have their primary tumor in place and are agreeable to up to 2 research biopsies of the primary tumor before and during (i.e., after 3 weeks of) Rebastinib therapy.

    Measured: Before and after cycle 1( week 3) for each patient.

Timeline

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

  1. First posted6 Jul 2016 (estimated)
  2. Study startJul 2016
  3. Primary completion27 Dec 2021
  4. Study completion27 Dec 2021

Why it stopped: Unfortunately, Deciphera management decided to not move forward with the rebastinib program and are terminating early.

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02824575
Sponsor's protocol ID
2016-6488
Status last verified
Mar 2022
First submitted
28 Jun 2016
Last updated
4 Apr 2022
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Rebastinib, Paclitaxel and Eribulin Mesylate in people with Breast Cancer and Breast Adenocarcinoma, run by Montefiore Medical 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 18 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: stopped early, as of the sponsor's last update on 4 Apr 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 was stopped early (reason given: Unfortunately, Deciphera management decided to not move forward with the rebastinib program and are terminating early.). 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?

Recommended Phase 2 dose(RP2D). (time frame: After 1 treatment cycle (3 weeks) during dose escalation cohort (N=24)). 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 NCT02824575.

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 4 Apr 2022.

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