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Advanced Breast CancerPhase 1NCT02599363

A Trial of Ribocilcib (LEE011) and Weekly Paclitaxel in Patients With Rb+ Advanced Breast Cancer

A Phase 1 study testing Ribociclib (LEE011) and Paclitaxel in people with Advanced Breast Cancer, run by Abramson Cancer Center at Penn Medicine 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 is a Phase I study to assess the safety and Maximum tolerated dose (MTD) of paclitaxel + ribociclib (LEE011) in patients with Rb+, advanced breast cancer. Dose escalation will be performed using standard 3 + 3 dosing strategy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Breast Cancer
What is being tested?
Ribociclib (LEE011) and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
Jan 2016to 12 Mar 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

  • Patient must have histologically or cytologically confirmed breast cancer that is now metastatic; any ER, PR or HER2 status is allowed.
  • Biopsy confirming metastatic breast cancer and Retinoblastoma protein (Rb) positivity by immunohistochemistry prior to enrolling on this protocol is required.
  • Biopsy must be obtained immediately before study enrollment; no intervening treatments are allowed.
  • Patient must have measurable disease defined by RECIST 1.1 criteria.
  • Age ≥18 years
  • Patient must have received ≤3 prior cytotoxic regimens in the metastatic setting.
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  • Performance status of 0-1 on the ECOG Performance Scale.
  • The subject must have adequate organ function, defined as follows
  • Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min
  • In the absence of liver metastases, alanine aminotransferase (AST) and aspartate aminotransferase (ALT) < 2.5 x ULN. If the patient has liver metastases, ALT and AST < 5 x ULN.
  • Total bilirubin < ULN; or total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN in patients with well documented Gilbert's Syndrome.
  • For subjects without extensive bone metastases: alkaline phosphatase levels < 2.5 x ULN
  • Potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication
  • INR ≤ 1.5 unless on warfarin in which case INR <3.0 is acceptable.
  • The subject must have adequate marrow function, defined as follows
  • Leukocytes Absolute neutrophil count (ANC) ≥1500/mm3
  • Platelets ≥100,000/mm3, and
  • Hemoglobin ≥9 g/dL
  • The subject must be able to swallow ribociclib (LEE011)

Who cannot join

  • Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of Study Day 1 or within 5 half-lives of the investigational product, whichever is longer, with the exception of a prior CDK 4/6 inhibitor.
  • Patient has had prior toxicity from a CDK 4/6 inhibitor necessitating discontinuation of the drug. Patient may have had prior treatment with a cdk 4/6 inhibitor in the adjuvant or metastatic setting.
  • Patient who has had chemotherapy or exposure to a CDK 4/6 inhibitor within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab) who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. Hormonal therapy must be discontinued at least 24 hours prior to starting study treatment.
  • Patient is unable to have a biopsy of a metastatic site for Rb testing, because the biopsy is felt to be too invasive or risky by the treating physician.
  • Patient has not received available therapies that confer clinical benefit.
  • Patient has known active CNS metastases and/or carcinomatous meningitis. However, patients with CNS metastases (including brain metastases) are eligible for the study provided they are clinically stable and have met ALL of the following criteria:
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  • At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
  • Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.
  • Patient has known hypersensitivity to any of the excipients of ribociclib
  • The subject has uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection
  • Diabetes mellitus
  • Symptomatic congestive heart failure (see 5.2.14), unstable angina pectoris, stroke or myocardial infarction within 12 months of screening
  • Patient has baseline neuropathy of ≥ grade 2.
  • Patients who have known allergic reactions to paclitaxel or IV contrast dye despite standard prophylaxis.
  • The subject is known to be positive for the human immunodeficiency virus (HIV). Note: baseline HIV screening is not required
  • The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
  • Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
  • Patient is not able to swallow oral medication and/or has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
  • Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV)
  • Documented cardiomyopathy
  • Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
  • History of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, long QT Syndrome or conduction abnormality within 12 months of screening
  • Congenital long QT syndrome or family history of long QT syndrome
  • Bradycardia (heart rate <50 at rest), by ECG or pulse, at screening
  • Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
  • On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF > 450 msec (using Fridericia's correction). All as determined by screening ECG (mean of triplicate ECGs)
  • Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug (see Table 6.2 for details):
  • Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
  • That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
  • That have a known risk to prolong the QT interval or induce Torsades de Pointes
  • Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or has not fully recovered from side effects of such treatment. The following uses of corticosteroids are permitted: single doses, topical application (e.g., for rash), inhaled sprays (e.g., for obstructive airway diseases), eye drops or local injections (e.g., intra-articular).
  • Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
  • Participation in a prior investigational therapeutic study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
  • Patient who has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom ≥ 25% of the bone marrow was irradiated.
  • Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (all surgical wounds must be fully healed). For the purpose of this criterion, a major surgical procedure is defined as one requiring the administration of general anesthesia (tumor biopsy is not considered as major surgery).
  • Patient has not recovered from all toxicities related to prior anticancer therapies to NCI-CTCAE version 4.03 Grade <1 (Exception to this criterion: patients with any degree of alopecia are allowed to enter the study).
  • Patient with a Child-Pugh score B or C
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation. Highly effective contraception methods include:
  • Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Combination of any two of the following (a+b or a+c or b+c) Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception Placement of an intrauterine device (IUD) or intrauterine system (IUS) Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository
  • In case of use of oral contraception, women should have been stable on the same pill before taking study treatment.
  • Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction.
  • Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Abramson Cancer Center of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: A Phase I Trial of Ribocilcib (LEE011) and Weekly Paclitaxel in Patients With Rb+ Advanced Breast Cancer

This is a Phase I study to assess the safety and Maximum tolerated dose (MTD) of paclitaxel + ribociclib (LEE011) in patients with Rb+, advanced breast cancer. Dose escalation will be performed using standard 3 + 3 dosing strategy. The starting dose of ribociclib (LEE011) is 200 mg once daily; dose escalation proceeds in 200 mg increments up to a maximum of 600 mg. Dose-limiting toxicities (DLT) will be based upon first-cycle toxicity.

Being tested
Ribociclib (LEE011), Paclitaxel

What participants receive

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

Study groups in NCT02599363
Study groupRoleWhat they receive
Dose Escalation Treatment ArmExperimentalNot described
Receives: Drug: Ribociclib (LEE011); Drug: Paclitaxel

What is being measured

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

  1. Number of Adverse Events

    Measured: 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 posted6 Nov 2015 (estimated)
  2. Study startJan 2016
  3. Primary completion12 Mar 2019
  4. Study completion12 Mar 2019

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
Sequential
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02599363
Sponsor's protocol ID
UPCC 06115
Status last verified
Nov 2023
First submitted
5 Nov 2015
Last updated
9 Nov 2023
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ribociclib (LEE011) and Paclitaxel in people with Advanced Breast Cancer, run by Abramson Cancer Center at Penn Medicine 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 19 inclusion and 49 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 9 Nov 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?

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?

Number of Adverse Events (time frame: 3 years). 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 NCT02599363.

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 9 Nov 2023.

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