Ribociclib and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors or Lymphoma

NCT02414724 | Terminated Phase 1

• 2 other identifiers: I 262914NCI-2015-00280
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of ribociclib and gemcitabine hydrochloride in treating patients with solid tumors or lymphoma that have spread to other places in the body and usually cannot be cured or controlled with treatment. Ribociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ribociclib together with gemcitabine hydrochloride may work better in treating patients with solid tumors or lymphoma.

Conditions

Lymphoma; Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• MTD of ribociclib and gemcitabine hydrochloride, defined as the maximum dose level at which =< 1/6 patients have dose limiting toxicities

  The frequency of toxicities will be tabulated for the dose estimated to be the MTD.

  21 days

• Recommended Phase II dose of ribociclib and gemcitabine hydrochloride, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0)

  21 days

Secondary Outcomes (7)

• CDK2/4/6, cyclin D1 and cyclin D3 amplification and RB, P16 expression in tumor tissue

  Baseline

• Disease free survival

  Up to 30 days after last dose of study drug

• Incidence of adverse events (AEs) of ribociclib and gemcitabine hydrochloride, using the NCI CTCAE v4.0

  Up to 30 days after last dose of study drug

• Objective response rate (ORR), calculated as the number of patients with a confirmed complete response (CR) or partial response (PR) divided by the total number of patients, using the RECIST 1.1

  Up to 30 days after last dose of study drug

• Overall survival

  From the start of treatment until death for any reason, assessed up to 30 days after last dose of study drug

Study Arms (1)

Treatment (ribociclib, gemcitabine hydrochloride)

EXPERIMENTAL

Patients receive ribociclib PO on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Ribociclib

Interventions

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011

Treatment (ribociclib, gemcitabine hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ribociclib, gemcitabine hydrochloride)

Pharmacological Study OTHER

Correlative studies

Treatment (ribociclib, gemcitabine hydrochloride)

Ribociclib DRUG

Given PO

Also known as: LEE-011, LEE011

Treatment (ribociclib, gemcitabine hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Patients must have advanced/metastatic solid malignancy or lymphoma for which no standard treatment option exists that will confer clinical benefit
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patients enrolled in the dose expansion phase must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria for solid tumors or measurable nodal disease at baseline as defined by Cheson criteria for lymphoma
• Written informed consent must be obtained prior to any screening procedures and according to local guidelines
• Life expectancy of \>= 12 weeks
• Absolute neutrophil count \>= 1.5 × 10\^9/L
• Platelets \>= 100 × 10\^9/L
• Hemoglobin \>= 9 g/dL
• Potassium above lower limit normal range for the institution; supplementation may be given before the first dose of study medication
• Total calcium (corrected for serum albumin if albumin abnormal) above lower limit normal range for the institution; supplementation may be given before the first dose of study medication
• Magnesium above lower limit normal range for the institution; supplementation may be given before the first dose of study medication
• Sodium above lower limit normal range for the institution; supplementation may be given before the first dose of study medication
• Phosphorus above lower limit normal range for the institution; supplementation may be given before the first dose of study medication
• International normalized ratio (INR) =\< 1.5
• Serum creatinine =\< 1.5 mg/dL or creatinine clearance \>= 50 mL/min (calculated by Cockcroft Gault equation)

You may not qualify if:

• Previous anti-cancer chemotherapy, immunotherapy or investigational agents \< 4 weeks prior to the first day of study defined treatment
• 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 (tumor biopsy is not considered as major surgery)
• Active clinically serious infections or other serious uncontrolled medical conditions
• Patient 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 baseline neuropathy of \> grade 2
• Patient has known hypersensitivity to any of the excipients of ribociclib
• Patient has a known history of human immunodeficiency virus (HIV) infection (testing not mandatory)
• Patients with central nervous system (CNS) involvement unless they meet 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
• Clinically significant, uncontrolled heart disease and/ or a history of cardiac dysfunction including any of the following:
• History of unstable angina pectoris, symptomatic pericarditis, myocardial infarction, coronary artery bypass grafting or coronary angioplasty within 12 months prior to study entry
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Documented cardiomyopathy

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Novartis: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

Gemcitabine; ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Opyrchal Mateusz

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 8, 2015
• First Posted: April 13, 2015
• Study Start: May 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: June 1, 2016
• Last Updated: July 25, 2022

Record last verified: 2022-07

Locations

US (1)