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

NCT03237390 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: MC1613NCI-2017-01316
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and best dose of ribociclib and gemcitabine hydrochloride in treating patients with solid tumors that have spread to other places in the body. Ribociclib may stop the growth of tumor 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 tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ribociclib and gemcitabine hydrochloride may work better in treating patients with solid tumors.

Conditions

Advanced Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least 2 patients (out of 6).

  Up to 21 days

Secondary Outcomes (4)

• Best response defined as best objective status recorded from the start of the treatment until disease progression/recurrence

  Up to 18 months

• Confirmed response defined to be a stringent complete response, complete response, very good partial response, or partial response

  Up to 18 months

• Incidence of adverse events

  Up to 30 days after last dose

• Pharmacokinetic (PK) of ribociclib

  Pre-ribociclib dose, 0.5, 1, 2, 4, 6, and 8 hours post dose on days 8 and 14 course 1 and pre-gemcitabine hydrochloride dose on day 1 course 2

Other Outcomes (1)

• CDK2/4/6, Cyclin D1 and Cyclin D3 amplification, retinoblastoma (RB) and P16 expression

  Up to 18 months

Study Arms (1)

Treatment (gemcitabine hydrochloride, ribociclib)

EXPERIMENTAL

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and ribociclib PO QD on days 8-14. 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, LY188011

Treatment (gemcitabine hydrochloride, ribociclib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (gemcitabine hydrochloride, ribociclib)

Pharmacological Study OTHER

Correlative studies

Treatment (gemcitabine hydrochloride, ribociclib)

Ribociclib DRUG

Given PO

Also known as: Kisqali, LEE-011, LEE011

Treatment (gemcitabine hydrochloride, ribociclib)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of advanced/metastatic solid malignancy for which no standard treatment option exists that will confer clinical benefit
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Dose expansion phase only: must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Ability to provide written informed consent which must be obtained prior to any screening procedures and according to local guidelines
• Life expectancy of \>= 12 weeks
• Absolute neutrophil count \>= 1500/mm\^3
• Platelets \>= 100,000/mm\^3
• Hemoglobin \>= 9 g/dL
• Potassium \>= lower limit of normal (LLN) range for the institution
• Calcium \>= LLN (corrected for serum albumin, if albumin abnormal)
• Magnesium \>= LLN
• Sodium \>= LLN
• Phosphorus \>= LLN; NOTE: 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 =\< 28 days prior to registration
• Received radiotherapy =\< 28 days or limited field radiation for palliation =\< 14 days prior to registration, 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
• Major surgery =\< 14 days prior to registration 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
• 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)
• Baseline neuropathy of \> grade 2
• Known hypersensitivity to any of the excipients of ribociclib
• Known human immunodeficiency virus (HIV) patients with active and untreated disease
• Central nervous system (CNS) involvement unless they meet ALL of the following criteria:
• \>= 28 days from prior therapy completion (including radiation and/or surgery) to registration
• 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 cardiac repolarization abnormalities including any of the following:
• History of unstable angina pectoris, symptomatic pericarditis, myocardial infarction, coronary artery bypass grafting or coronary angioplasty =\< 12 months prior to registration
• History of documented congestive heart failure (New York Heart Association functional classification III - IV)
• Documented cardiomyopathy

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• Norman A, Seetharam M, Allred J, Kong J, Opyrchal M, Ma WW, Lou Y, Dy GK, Mahipal A, Weroha SJ, Wahner Hendrickson AE, Reid JM, Adjei AA. A phase I study of the CDK4/6 inhibitor ribociclib combined with gemcitabine in patients with advanced solid tumors. BJC Rep. 2025 Jan 14;3(1):1. doi: 10.1038/s44276-024-00107-0.

  PMID: 39809926 DERIVED

• Seetharam M, Norman A, Allred J, Kong J, Opyrchal M, Ma WW, Lou Y, Dy GK, Mahipal A, Weroha J, Wahner-Hendrickson A, Reid JM, Adjei AA. A Phase I Study of sequences of the CDK4/6 Inhibitor, Ribociclib Combined with Gemcitabine in Patients with Advanced Solid Tumors. Res Sq [Preprint]. 2024 Apr 25:rs.3.rs-4261257. doi: 10.21203/rs.3.rs-4261257/v1.

  PMID: 38746220 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Gemcitabine; ribociclib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Alex Adjei

  Mayo Clinic

  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: July 31, 2017
• First Posted: August 2, 2017
• Study Start: January 4, 2018
• Primary Completion: May 17, 2022
• Study Completion: May 17, 2022
• Last Updated: January 5, 2023

Record last verified: 2022-09

Locations

US (3)