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Thyroid CancerPhase 2NCT01270321

Pasireotide & Everolimus in Adult Patients With Radioiodine-Refractory Differentiated & Medullary Thyroid Cancer

A Phase 2 study testing Everolimus, Pasireotide and Everolimus and Pasireotide in people with Thyroid Cancer, run by Emory University at 3 sites 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

The purpose of this study is to determine the effectiveness of two anticancer drugs, everolimus and pasireotide, in patients with thyroid cancer when the cancer is no longer responding to treatment with radioiodine or where it is deemed unsafe for the patient to receive additional radioiodine treatment. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thyroid Cancer
What is being tested?
Everolimus, Pasireotide and Everolimus and Pasireotide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
3 sitesUnited States
Study dates
Nov 2010to Feb 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

  • Histologic or cytologic confirmation of thyroid cancer (papillary, follicular, medullary); histologic variants such as Hurthle and tall cell variants are allowed.
  • Biochemical or radiologic documentation of disease progression within the last 12 months prior to enrollment.
  • Presence of at least one site of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
  • Patient must have radioiodine refractory disease as defined by one or more of the following conditions:
  • All cases of medullary thyroid carcinoma.
  • No iodine-uptake on a post- radioactive iodine treatment scan (in presence of low iodine diet and thyroid stimulating hormone (TSH) suppression) in an anatomically defined lesion that qualifies as target lesion by RECIST criteria.
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  • OR
  • If there is demonstrable iodine-uptake: the last radioiodine therapy of (≥ 100 mCi) was given within the last 16 months OR if given more than 16 months before enrollment, there is evidence of disease progression after each of the last two radioiodine treatment performed within 16 months of each other (each dose should be ≥ 100mCi).
  • OR
  • If the patient has received the maximum cumulative life time dose of radioactive iodine treatments of at least 600 mCi.
  • If the patient declines or is intolerant of radioiodine therapy or if with progressive disease that is, in the opinion of the treating physician, likely to benefit from biologic therapy rather than further iodine therapy e.g. patient with heavy burden of disease
  • Age ≥ 18 years.
  • Minimum of four weeks since any major surgery or since completion of radiation (patients should have adequately recovered from the acute toxicities of any prior therapy).
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
  • Life expectancy of at least 6 months.
  • Adequate bone marrow function as shown by: absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L, platelets ≥ 100 x 10⁹/L, Hgb > 9 g/dL.
  • Adequate liver function as shown by: serum bilirubin ≤ 1.5 x upper limit of normal (ULN), and serum transaminases activity ≤ 3 x ULN, with the exception of serum transaminases (< 5 x ULN) if the patient has liver metastases.
  • Adequate renal function as shown by serum creatinine ≤ 1.5 x ULN or glomerular filtration rate (GFR) of 60cc/ml using the formula of Cockroft and Gault.
  • Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days of the administration of the first study treatment. Women must not be lactating. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study.
  • Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information.
  • International normalized ratio (INR) and prothrombin time (PTT) ≤ 1.5 x ULN. (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of low molecular weight [LMW] heparin for > 2 weeks at time of randomization.)

Who cannot join

  • Prior treatment with not more than 1 systemic agent.
  • Patients who have undergone major surgery within 4 weeks prior to study enrollment (tracheotomy, feeding tube or vascular access catheter placement and interventional procedures such as bronchoscopy, upper GI endoscopy or colonoscopy are not considered major surgery).
  • Chronic treatment with systemic steroids or another immunosuppressive agent.
  • Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry.
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
  • Patients with prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years.
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  • Patients with uncontrolled diabetes mellitus or a fasting plasma glucose > 1.5 ULN. Note: At the principal investigator's discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted.
  • Patients with symptomatic cholelithiasis (asymptomatic gall stone discovered on screening US should be reviewed by the PI but will not lead to automatic exclusion).
  • Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C):
  • History of liver disease, such as cirrhosis or chronic active hepatitis B and C.
  • Presence of Hepatitis B surface antigen (HbsAg).
  • Presence of Hepatitis C antibody test (anti-HCV).
  • Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment.
  • QT related exclusion criteria:
  • QT corrected Fridericia's method (QTcF) at screening > 470 msec.
  • History of syncope or family history of idiopathic sudden death.
  • Sustained or clinically significant cardiac arrhythmias.
  • Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade atrioventricular (AV) block.
  • Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure.
  • Concomitant medication(s) known to increase the QT interval.
  • Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (ELISA and Western blot).
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • Severely impaired lung function (as defined as spirometry and diffusing capacity of lung for carbon monoxide [DLCO] that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air).
  • Any active (acute or chronic) or uncontrolled infection/disorders.
  • Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (everolimus).
  • Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving treatment with pasireotide or RAD001.
  • History of, or current alcohol misuse/abuse within the past 12 months.
  • Acute or chronic pancreatitis.
  • Women who are pregnant or breast feeding, or women/men of reproductive potential who are not using and unwilling to practice an effective method of birth control. (Women of childbearing potential [WOCBP] must have a negative serum pregnancy test within 7 days prior to administration of pasireotide and RAD001.)
  • Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment.
  • Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients.
  • Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR formulations.
  • History of noncompliance to medical regimens.
  • Patients unwilling to or unable to comply with the protocol.
  • Patients taking medications known to be strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: A 3-Arm Randomized Phase II Trial Evaluating Single Agent and Combined Efficacy of Pasireotide and Everolimus in Adult Patients With Radioiodine-Refractory Differentiated and Medullary Thyroid Cancer

The purpose of this study is to determine the effectiveness of two anticancer drugs, everolimus and pasireotide, in patients with thyroid cancer when the cancer is no longer responding to treatment with radioiodine or where it is deemed unsafe for the patient to receive additional radioiodine treatment. The investigators also want to establish the best manner of taking the two medications when used together to treat thyroid cancer. In particular, the investigators want to know if it is better to give both at the same time or add a second medication after the first one has stopped working.

This study will also look at specific substances called biomarkers in your blood, and in the tumor tissue which are involved in the growth of tumor cells, and determine if the levels of these biomarkers are related to your response to treatment or development of side effects.

Read more

Everolimus, also known by the brand name, Afinitor, is a biologic drug approved by the Food and Drug Administration (FDA) for the treatment of kidney cancer. It works by preventing cancer cells from multiplying and it also makes them more likely to die from the treatment.

Pasireotide also known by the name, SOM230 is a new medication that is not yet approved by the FDA for the treatment of cancer. It is a newer form of a drug called octreotide, which is approved for the treatment of cancer arising from endocrine organs. Pasireotide works by binding to a protein called somatostatin receptor, which is expressed in many tissues throughout the body including thyroid cancer cells. Pasireotide prevents the action of somatostatin by binding to these receptors.

Conditions
Thyroid Cancer
Being tested
Everolimus, Pasireotide, Everolimus and Pasireotide
Keywords
Thyroid Cancer
Medical subject headings
Thyroid Neoplasms

What participants receive

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

  • EverolimusDrug

    Also called Afinitor, RAD001

    Everolimus 10 mg daily continuously (switch to 2-drug combination at progression if no intolerable toxicity)

  • PasireotideDrug

    Also called SOM230

    Pasireotide 1200 mcg bid for 4 weeks followed by Pasireotide long acting release (LAR) 60 mg i.m. once every 4 weeks

  • Everolimus and PasireotideDrug

    Also called Afinitor, SOM230

    Everolimus 10 mg daily continuously together with Pasireotide 1200 mcg bid for 4 weeks followed by Pasireotide long acting release (LAR) 60 mg i.m. once every 4 weeks

Study groups in NCT01270321
Study groupRoleWhat they receive
Arm A (Everolimus alone)ExperimentalCURRENTLY CLOSED TO ACCRUAL--Everolimus alone followed by Everolimus + Pasireotide at the time of progression
Receives: Drug: Everolimus
Arm B (Pasireotide alone)ExperimentalCURRENTLY CLOSED TO ACCRUAL--Pasireotide alone followed by Everolimus + Pasireotide at the time of progression
Receives: Drug: Pasireotide
Arm C (Everolimus + Pasireotide)ExperimentalCURRENTLY CLOSED TO ACCRUAL
Receives: Drug: Everolimus and Pasireotide

What is being measured

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

  1. Number of Participants With Response Per Responsive Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0)

    Number of participants with response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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: Through study completion, an average of 1 year

Secondary outcomes (1)

  1. Number of Participants With Progression-free Survival

    Time from starting treatment until disease progression as defined using Response Evaluation CriteriaIn Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions", or death.

    Measured: Through study completion, an average of 1 year

Timeline

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

  1. First posted5 Jan 2011 (estimated)
  2. Study startNov 2010
  3. Primary completionFeb 2019
  4. Study completionFeb 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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01270321
Sponsor's protocol ID
IRB00041909
Other IDs
WCI1777-09
Status last verified
Feb 2021
First submitted
4 Jan 2011
Last updated
17 Feb 2021
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus, Pasireotide and Everolimus and Pasireotide in people with Thyroid Cancer, run by Emory University at 3 sites 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 22 inclusion and 36 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 17 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 25 Aug 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 Per Responsive Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) (time frame: Through study completion, an average of 1 year). 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 NCT01270321.

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 17 Feb 2021.

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