Overview

This trial is active, not recruiting.

Condition gastrointestinal cancer
Treatment lee011
Phase phase 2
Targets CDK4, CDK6
Sponsor M.D. Anderson Cancer Center
Collaborator Novartis
Start date August 2015
End date August 2018
Trial size 21 participants
Trial identifier NCT02420691, 2014-0371, NCI-2015-01017

Summary

The goal of this clinical research study is to learn if LEE011 can help to control advanced neuroendocrine tumors of the foregut. The safety of this drug will also be studied.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients treated with LEE011 600 mg by mouth daily 3 weeks on/1 week off in 28 day cycles. Participants allowed to remain on study until disease progression or unacceptable toxicities
lee011
600 mg by mouth daily on Days 1 - 21 of a 28 day cycle.

Primary Outcomes

Measure
Overall Response of LEE011 in Participants With Foregut Neuroendocrine Tumors (NETs)
time frame: After 3, 21 day cycles

Secondary Outcomes

Measure
Clinic Benefit Rate of LEE011 in Participants With Foregut Neuroendocrine Tumors (NETs)
time frame: 6 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Histologically or cytologically confirmed low or intermediate grade, unresectable well differentiated foregut neuroendocrine tumors (thymic, bronchopulmonary, gastric, duodenal and pancreatic). Patients with multiple neuroendocrine tumors associated with MEN1 syndrome will be eligible. 2. Patients must have radiographically measurable disease. 3. Pancreatic neuroendocrine patients must have had progression after prior therapy. Patients with other foregut neuroendocrine tumors must have had progressive disease over the last 12 months, irrespective of prior therapy. Patients with both functional (who may continue somatostatin analogues as required for control of related symptoms) and non-functional tumors are eligible. In patients who have previously received therapy, the number of prior lines of therapy should not be more than 2 lines of systemic therapy not including somatostatin analogues. 4. Written informed consent must be obtained prior to any screening procedures. 5. Age greater than or equal to 18 years. 6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1. 7. A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies and major surgery) and enrollment, to allow the effects of prior therapy to have abated: a) Cytotoxic or targeted chemotherapy: greater than or equal to the duration of the cycle of the most recent treatment regimen (a minimum of 3 weeks for all regimens, except 6 weeks for nitrosoureas and mitomycin-C). b) Biologic therapy (e.g., antibodies): greater than or equal to 4 weeks. 8. Patients must have adequate organ function, as defined by the following parameters: a. Bone marrow: Absolute Neutrophil Count (ANC) greater than or equal to 1.5 x 10^9/L; Hemoglobin (Hgb) greater than or equal to 9 g/dL; Platelets greater than or equal to 100 x 10^9/L. b. Hepatic function: Serum total bilirubin less than or equal to 1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and ALT (SGPT) less than or equal to 2.5 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT less than or equal to 5 x ULN. 9. (continued from above) c. Renal function: Serum creatinine less than or equal to 1.5 x ULN or 24-hour clearance greater than or equal to 50 mL/min; Serum potassium, sodium, magnesium, phosphorus, and total calcium (corrected for serum albumin) must be within clinically relevant limits (e.g., a patient can be enrolled if a lab value may be outside the normal laboratory range but the abnormality is not clinically relevant or can be repleted.) 10. Negative pregnancy test (serum B-HCG) within 7 days of starting study treatment is required in women of childbearing potential. B-HCG may be secreted by a small percentage of NETs and be a tumor marker. Thus, NET patients with positive B-HCG are eligible if pregnancy can be excluded by vaginal ultrasound or lack of expected doubling of B-HCG. Exclusion Criteria: 1. Patient has a known hypersensitivity to LEE011 or any of its excipients. 2. Patients with known or suspected brain metastases. However, if radiation therapy and/or surgery has been completed and serial evaluation by CT (with contrast enhancement) or MRI over a minimum of 3 months demonstrates the disease to be stable and if the patient remains asymptomatic, then the patient may be enrolled. Such patients must have no need for treatment with steroids or anti-epileptic medications. 3. Patients with concurrent malignancies or malignancies within 3 years prior to starting study drug (with the exception of tumors common to a single genetic cancer syndrome, i.e. MEN1, MEN2, vHL, TSC etc., or adequately treated, basal cell skin cancer, squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer). 4. 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). 5. Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C (testing is not mandatory). 6. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation in the clinical study (e.g. chronic pancreatitis, chronic active hepatitis, etc.). 7. Patient who has received radiotherapy within less than or equal to 4 weeks or limited field radiation for palliation within less than or equal to 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 greater than or equal to 30% of the bone marrow was irradiated. 8. 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). 9. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a) History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis less than 12 months prior to screening b) History of documented congestive heart failure (New York Heart Association functional classification III-IV) c) Documented cardiomyopathy d) Patient has a Left Ventricular Ejection Fraction (LVEF) less than 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening e) History of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, long QT Syndrome or conduction abnormality within 12 months prior to starting study drug 10. (continued from above) f) Congenital long QT syndrome or a family history of QTc prolongation g) 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) 11. Systolic blood pressure greater than 160 mmHg or less than 90 mmHg at screening. 12. Patients who are currently receiving treatment with agents that are known to cause QTc prolongation or inducing Torsades de Pointes in humans and are unable to discontinue or switch to an alternate medication. 13. Patients who are currently receiving treatment (within 5 days prior to starting study drug) with agents that are known strong inducers or inhibitors of CYP3A4/5, or that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5. 14. Patients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., uncontrolled diabetes mellitus defined by a glucose greater than 1.5 ULN in spite of adequate medical treatment, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection) 15. Patient has a history of non-compliance to medical regimen or inability to grant consent. 16. Pregnant or 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 (greater than 5 mIU/mL). 17. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using 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. 18. (continued from above) Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient; Combination of any of the two following (a+b or a+c or b+c) a. 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 b. Placement of an intrauterine device (IUD) or intrauterine system (IUS) c. 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. 19. (continued from above) 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. 20. Sexually active males unless they use a condom during intercourse while taking the drug and for 21 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. 21. Patients unwilling or unable to comply with the protocol. 22. 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.

Additional Information

Official title A Phase II Study of LEE011 (Ribociclib) in Patients With Advanced Neuroendocrine Tumors of Foregut Origin (CLEE011 XUS02T)
Principal investigator Nageshwara V. Dasari, MBBS
Description Study Drug Administration: Each study cycle is 28 days. If you are found to be eligible to take part in this study, you will take LEE011 capsules by mouth 1 time on Days 1-21 of each cycle. You will take LEE011 capsules whole, at about the same time each morning, with or without food, with at least 1 cup (8 ounces) of water. Do not chew or open the capsules unless a member of the study staff tells you to do so. If you forget to take your dose, you can still take the study drug up to 6 hours later. If you are more than 6 hours late, wait until your next scheduled dose. If you vomit after taking a dose, do not take an extra dose. Tell the study doctor or nurse if you vomit after taking LEE011. Study Visits: On Day 1 of Cycle 1: - You will have a physical exam. - Blood (about 3 teaspoons) will be drawn for routine tests. If you are taking drugs to prevent blood clots, this blood draw will also be used to check how well your blood clots. On Day 15 of Cycle 1: - You will have a physical exam. - Blood (about 2 teaspoons) will be drawn for routine tests. - You will have an EKG before your dose of LEE011. On Day 1 of Cycle 2: - You will have a physical exam. - You will have an EKG before your dose of LEE011. - Blood (about 2 teaspoons) will be drawn for routine tests. If you are taking drugs to prevent blood clots, this blood draw will also be used to check how well your blood clots. - You will have an image-guided tumor biopsy for PD testing. On Day 15 of Cycle 2 and Day 1 of Cycle 3, you will have an EKG before and up to 4 hours after your dose of LEE011. On Day 1 of Cycles 3 and beyond: - You will have a physical exam. - Blood (about 2 teaspoons) will be drawn for routine tests. If you are taking drugs to prevent blood clots, this blood draw will also be used to check how well your blood clots. On Day 1 of Cycle 2, Day 1 of Cycle 4, and then every 3 cycles after that (Cycles 7, 10, 13, and so on), blood (about 2 teaspoons) will be drawn for tumor marker testing. If the study doctor thinks it is needed, you may have this blood draw performed more frequently. The study doctor will discuss this with you. Every 3 cycles (Cycles 3, 6, 9, and so on), you will have an MRI, CT, and/or Octreoscan to check the status of the disease. On Day 1 of Cycles 4-6, you will have an EKG before your dose of LEE011. Every 4 cycles (Cycles 4, 8, 12, and so on), blood (about 2 teaspoons) will be drawn to check how much fat and cholesterol is in your blood. You should fast for at least 8 hours before this blood draw. Length of Treatment: You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on this study will be over after the end-of-treatment visit, unless you have side effects. End-of-Treatment Visit: Within 28 days after your last dose of study drug: - You will have a physical exam. - You will have an EKG and either an ECHO or a MUGA scan. - Blood (about 2 tablespoons) and urine will be collected for routine tests, including a test to to check how much fat and cholesterol is in your blood. You should fast for at least 8 hours before this blood draw. If you are taking drugs to prevent blood clots, this blood draw will also be used to check how well your blood clots. If you have any side effects or symptoms, you will either be called by a member of the study staff or asked to come into the clinic until the side effects or symptoms are gone or become stable. If you are called, each call should last about 10 minutes. This is an investigational study. LEE011 is not FDA approved or commercially available. It is currently being used for research purposes. The study doctor can explain how the study drug is designed to work. Up to 20 participants will be enrolled in this study. All will take part at MD Anderson.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.
Location data was received from the National Cancer Institute and was last updated in September 2016.