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Advanced Digestive System Neuroendocrine NeoplasmPhase 2NCT02420691

Ribociclib in Treating Patients With Advanced Neuroendocrine Tumors of Foregut Origin

A Phase 2 study testing Laboratory Biomarker Analysis, Pharmacological Study and Ribociclib in people with Advanced Digestive System Neuroendocrine Neoplasm and Duodenal Neuroendocrine Tumor G1, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well ribociclib works in treating patients with neuroendocrine tumors of the foregut, which includes the thymus, lung, stomach, and pancreas, that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced tumors). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pharmacological Study and Ribociclib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
25 Aug 2015to 5 Jun 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Patients must have radiographically measurable disease
  • 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
  • Written informed consent must be obtained prior to any screening procedures
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
  • 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
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  • 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
  • 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 alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [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
  • 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 (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)
  • Sodium (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)
  • Magnesium (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)
  • Phosphorus (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)
  • 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)
  • Negative pregnancy test (serum beta-human chorionic gonadotropin [B-HCG]) within 7 days of starting study treatment is required in women of childbearing potential; NET patients with positive B-HCG are eligible if pregnancy can be excluded by vaginal ultrasound or lack of expected doubling of B-HCG

Who cannot join

  • Patient has a known hypersensitivity to LEE011 or any of its excipients
  • Patients with known or suspected brain metastases; however, if radiation therapy and/or surgery has been completed and serial evaluation by computed tomography (CT) (with contrast enhancement) or magnetic resonance imaging (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
  • 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, von Hippel-Lindau [vHL], tuberous sclerosis complex [TSC] etc., or adequately treated, basal cell skin cancer, squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer)
  • 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)
  • Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C (testing is not mandatory)
  • 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.)
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  • 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
  • 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)
  • 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 f) congenital long QT syndrome or a family history of corrected QT interval (QTc) prolongation g) on screening, inability to determine the corrected QT for Fridericia (QTcF) interval on the electrocardiogram (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)
  • Systolic blood pressure greater than 160 mmHg or less than 90 mmHg at screening
  • Patients who are currently receiving treatment with agents that are known to cause QTc prolongation or inducing Torsade de Pointes in humans and are unable to discontinue or switch to an alternate medication
  • Patients who are currently receiving treatment (within 5 days prior to starting study drug) with agents that are known strong inducers or inhibitors of cytochrome P450, family 3, subfamily A polypeptide 4 (CYP3A4)/cytochrome P450, family 3, subfamily A polypeptide 5 (5), or that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
  • 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)
  • Patient has a history of non-compliance to medical regimen or inability to grant consent
  • 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)
  • 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; 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; 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
  • 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
  • Patients unwilling or unable to comply with the protocol
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase II Study of LEE011 (Ribociclib) in Patients With Advanced Neuroendocrine Tumors of Foregut Origin

This phase II trial studies how well ribociclib works in treating patients with neuroendocrine tumors of the foregut, which includes the thymus, lung, stomach, and pancreas, that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced tumors). Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the Response Evaluation Criteria in Solid Tumors (RECIST) (per version 1.1) objective response rate of LEE011 (ribociclib) among patients with advanced foregut neuroendocrine tumors (NETs).

SECONDARY OBJECTIVES:

  1. To evaluate the progression free survival duration of LEE011 among patients with advanced foregut NETs.

II. To evaluate the safety and tolerability of LEE011 in patients with advanced foregut NETs.

III. To determine clinic benefit rate at 6 months (defined as complete response plus partial response plus stable disease) with LEE011 among patients with advanced foregut NETs.

EXPLORATORY OBJECTIVES:

  1. To determine baseline molecular markers (mutations, deletions, and amplifications in multiple endocrine neoplasia [MEN]1, p27, p16 and cyclin D1 [CCND1]) in archival tumor that may predict clinical benefit at 6 months from LEE011.

II. To determine potential mechanisms/markers of resistance. III. To determine early chromogranin and neuron specific enolase responses in patients with elevated levels at baseline.

IV. To determine the pharmacodynamic changes including proliferation-related Ki-67 antigen (Ki-67) and phosphorylated retinoblastoma (pRb) upon treatment with LEE011 in patients with advanced foregut NETs.

OUTLINE:

Patients receive ribociclib orally (PO) once daily (QD) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Being tested
Laboratory Biomarker Analysis, Pharmacological Study, Ribociclib
Medical subject headings
Non functioning pancreatic endocrine tumor, Thymus Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • RibociclibDrug

    Also called Kisqali, LEE-011, LEE011

    Given PO

Study groups in NCT02420691
Study groupRoleWhat they receive
Treatment (ribociclib)ExperimentalPatients receive ribociclib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Ribociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: 3 years 10 months

Secondary outcomes (2)

  1. Number of Participants With Clinical Benefit Rate

    Number of Participants that did not have progressive disease at 6 months.

    Measured: At 6 months

  2. Progression Free Survival (PFS)

    PFS is the length of time during and after the treatment that a participant lives with the disease but it does not get worse.The Kaplan-Meier (KM) method will be used to estimate the PFS.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2015 (estimated)
  2. Study start25 Aug 2015
  3. Primary completion5 Jun 2019
  4. Study completion5 Jun 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02420691
Sponsor's protocol ID
2014-0371
Other IDs
NCI-2015-01017, 2014-0371, P30CA016672
Status last verified
Oct 2020
First submitted
15 Apr 2015
Last updated
30 Oct 2020
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Pharmacological Study and Ribociclib in people with Advanced Digestive System Neuroendocrine Neoplasm and Duodenal Neuroendocrine Tumor G1, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 (time frame: 3 years 10 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02420691.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2020.

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