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

NCT02599363 | Completed Phase 1 DMC

• 1 other identifier: UPCC 06115
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events

  3 years

Study Arms (1)

Dose Escalation Treatment Arm

EXPERIMENTAL

Drug: Ribociclib (LEE011); Drug: Paclitaxel

Interventions

Ribociclib (LEE011) DRUG

Dose Escalation Treatment Arm

Paclitaxel DRUG

Dose Escalation Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Interventions

ribociclib; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Amy Clark, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2015
• First Posted: November 6, 2015
• Study Start: January 1, 2016
• Primary Completion: March 12, 2019
• Study Completion: March 12, 2019
• Last Updated: November 9, 2023

Record last verified: 2023-11

Locations

US (1)