Managed Access Program to Provide Access to Ribociclib, for Locally Advanced or Metastatic Cancer Resistant or Refractory to Available Treatment Options and Candidate for Therapy With a CDK Inhibitor

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

No longer available

CT.gov ID

NCT05038631

Collaborator

(none)

Study Details

Study Description

Brief Summary

The purpose of this Managed Access Program (MAP) Cohort Treatment Plan is to provide guidance to the Physician for the treatment and monitoring of patients in the Cohort MAP.

The Physician should follow the suggested treatment guidelines. Furthermore, the Physician must comply with the MAP Agreement Letter and applicable local laws and regulations.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Ribociclib

Detailed Description

Prior to inclusion of a patient in the Cohort, the requesting Physician must submit a request for access to the product in GEMS (Grants, External Requests and Managed Access System) accessible through https://www.novartis.com/our-focus/healthcare-professionals/managed-access-programs providing the rationale for the request and relevant medical history of the patient.

The request is then assessed against the MAP and Cohort inclusion/exclusion criteria by the medical team experienced with the product and indication. Upon the required approvals, the patient is included in the Cohort.

Study Design

Study Type:

Expanded Access

Official Title:

Managed Access Program (MAP) Cohort Treatment Plan CLEE011A2408 to Provide Access to Ribociclib (LEE011, Kisqali®), for Locally Advanced or Metastatic Cancer Resistant or Refractory to Available Treatment Options and Candidate for Therapy With a CDK Inhibitor (Including Tumors With D-cyclin-CDK4/6-INK4a-Rb Pathway Abnormalities)

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Written informed consent must be obtained prior to any screening procedures, according to local, regional or national guidelines
Patient is an adult male/female ≥ 18 years of age at the time of informed consent
If patient is receiving tamoxifen or toremifene, a washout period of 5 half-lives prior to treatment initiation is required
Patient is postmenopausal. Postmenopausal status is defined either by:
Prior bilateral oophorectomy, Age ≥60, Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and (FSH) and estradiol in the postmenopausal range per local laboratory normal range.

If taking tamoxifen or toremifene and age <60, then FSH and plasma estradiol level in postmenopausal range. (NCCN v4 2018) Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure postmenopausal status (NCCN Guidelines Version 2.2017). Ovarian radiation or treatment with a luteinizing hormone-releasing hormone agonist (LH-RH) is not permitted for induction of ovarian suppression in this treatment plan.

Patient is premenopausal or perimenopausal at the time of treatment plan entry.

Premenopausal status is defined as either:

Patient had last menstrual period within the last 12 months, OR If on tamoxifen or toremifene, plasma estradiol and FSH are in the premenopausal ranges according to central /local laboratory definition OR In case of therapy-induced amenorrhea, plasma estradiol and/or FSH are in the premenopausal ranges according to central/local laboratory definition Patients who have undergone bilateral oophorectomy are not eligible. Perimenopausal status is defined as neither premenopausal nor postmenopausal
For pre-menopausal patients: Confirmed negative serum pregnancy test (β-hCG) before starting treatment or patient has had a hysterectomy
If applicable: Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory.
If applicable Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an ICH status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample
Patient has locally advanced or metastatic cancer resistant or refractory to available treatment options
Evidence of activation of the cyclin D-CDK4/6 pathway abnormalities (Examples of abnormalities are: CDK4 amplification or mutation; CDK6 amplification or mutation; Cyclin D1 amplification, Cyclin D3 amplification or p16 (CDKN2A) mutation); OR available data supporting the activity of ribociclib in a specific tumor type (with or without specific patient selection based on biomarkers)
Patient has evidence of recurrence or progression on or after the last systemic therapy prior to enrollment
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Patient has adequate bone marrow and organ function as defined by the following laboratory values: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, Platelets ≥ 100 × 109/L, Hemoglobin ≥ 9.0 g/dL, INR ≤1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to the first dose of study drug), Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min 1.73m2 according to the Modification of Diet in Renal Disease (MDRD) formula, INR ≤1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to the first dose of study drug), Serum creatinine ≤ 1.5 mg/dL, Total bilirubin < ULN except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN, Alanine aminotransferase (ALT) < 2.5 x ULN; except for patients with liver metastasis, who are only included if the ALT is < 5 × ULN, Aspartate aminotransferase (AST) < 2.5 x ULN; except for patients with liver metastasis, who are only included if the AST is < 5 × ULN, Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements before the first dose of ribociclib treatment: Potassium, Magnesium, Total Calcium (corrected for serum albumin).
Standard 12-lead Electrocardiogram (ECG) values defined as the mean of the triplicate ECGs with the following parameters at screening: QT interval at screening < 450 msec (using Fridericia's correction), Mean resting heart rate 50-90 (bpm) (determined from the ECG).
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2. Data from C-1 study shows that ribociclib is safe even with ECOG 2
Patient is able to swallow 200 mg ribociclib tablets
Patients must be able to communicate with the investigator and comply with the requirements of the treatment plan.
Patient has failed available standard of care treatment options and has no other available comparable or satisfactory alternative treatment options
Patient is not eligible for participation in any ongoing clinical trials with ribociclib, or has recently completed a clinical trial with ribociclib that has been terminated, and after considering other options (e.g., trial extensions, amendments, etc.), the Novartis clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient
Patient is not being transferred from an ongoing clinical trial for which they are still eligible

Exclusion Criteria:

Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment
Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant any CDK4/6 inhibitor
Patient with a known hypersensitivity to any of the excipients of ribociclib or combination drug with an established Recommended Phase 2 Dose (RP2D) for the specific combination. If film- coated tablet formulation is used : "including to peanut and soy".
Patient is concurrently using other anti-cancer therapy.
Patient has had major surgery within 14 days of the first dose of ribociclib or has not recovered from major side effects. Tumor biopsy, gastrostomy, insertion of a gastric feeding tube, ventriculo peritoneal shunt, endoscopic ventriculostomy and central venous access are not considered major surgery.
Patient has not recovered from clinical and laboratory acute toxicities related to prior anticancer therapies to NCI version 4.03 Grade ≤1. Exception to this criterion: patients with any grade 1 taxane-induced neuropathy , any grade of alopecia amenorrhea or other toxicities not considered a safety risk for the patient as per investigator's discretion, are allowed to enter the treatment plan.
Patient has received extended-field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization, and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion). Patient from whom ≥ 25% (Ellis 1961) of the bone marrow has been previously irradiated are also excluded.
Based on the physician's evaluation completion of any complication/toxicity from any intervention (including radiotherapy and/or surgery) before to starting the ribociclib treatment
Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the treatment plan drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
Patient has a known history of HIV)infection (testing not mandatory)
Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the treating physician's judgment cause unacceptable safety risks, contraindicate patient participation in the Managed Access Program (MAP) or compromise compliance with the MAP: (e.g., chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.)
Clinically significant uncontrolled heart disease and/or cardiac repolarization abnormalities including any of the following:

History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to MAP entry Documented cardiomyopathy Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition scan or echocardiogram Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia, Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause TdP that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting ribociclib treatment), Inability to determine the QTcF interval .

Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block) Systolic Blood Pressure >160 or <90 mmHg

Patient is currently receiving any of the following substances: Concomitant medications, herbal supplements, and/or fruits (e.g., grapefruit, pummelo, star fruit, Seville oranges, pomegranate) and their juices that are strong inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4/5), Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
Avoid particularly concurrent use of systemic corticosteroids
Not able to understand and to comply with treatment plan instructions and requirements. If applicable
Pregnant or nursing (lactating) women or women who to become pregnant or breast-feed during the study
Women of child-bearing potential defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the study treatment and for 21 days after stopping the treatment. 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), total hysterectomy or tubal ligation at least 6 weeks before taking treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, Male partner sterilization (at least 6 months prior to screening). For female patients on the treatment plan, the vasectomized male partner should be the sole partner for that patient and the success of the vasectomy must be medically confirmed as per local practice, Placement of an intrauterine device (IUD), Note: Use of oral (estrogen and progesterone), transdermal, injected or implanted hormone containing intrauterine systems (IUS) or any other hormonal methods of contraception as well as hormonal replacement therapy is not allowed in this study.