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

NCT01270321 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB00041909WCI1777-09
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief 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. 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. 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

Keywords

Thyroid Cancer

Outcome Measures

Primary Outcomes (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."

  Through study completion, an average of 1 year

Secondary Outcomes (1)

• Number of Participants With Progression-free Survival

  Through study completion, an average of 1 year

Study Arms (3)

Arm A (Everolimus alone)

EXPERIMENTAL

CURRENTLY CLOSED TO ACCRUAL--Everolimus alone followed by Everolimus + Pasireotide at the time of progression

Drug: Everolimus

Arm B (Pasireotide alone)

EXPERIMENTAL

CURRENTLY CLOSED TO ACCRUAL--Pasireotide alone followed by Everolimus + Pasireotide at the time of progression

Drug: Pasireotide

Arm C (Everolimus + Pasireotide)

EXPERIMENTAL

CURRENTLY CLOSED TO ACCRUAL

Drug: Everolimus and Pasireotide

Interventions

Everolimus DRUG

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

Also known as: Afinitor, RAD001

Arm A (Everolimus alone)

Pasireotide DRUG

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

Also known as: SOM230

Arm B (Pasireotide alone)

Everolimus and Pasireotide DRUG

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

Also known as: Afinitor, SOM230

Arm C (Everolimus + Pasireotide)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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).
• 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.

You may not qualify if:

• 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.
• 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.
• 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 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.

Sponsors & Collaborators

• Emory University: lead
• Novartis: collaborator

Study Sites (3)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

Everolimus; pasireotide

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Taofeek Owonikoko
• Organization: Emory University

TOWONIK@emory.edu

404-778-5575

Study Officials

• Taofeek Owonikoko, MD, PhD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 4, 2011
• First Posted: January 5, 2011
• Study Start: November 1, 2010
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: February 17, 2021
• Results First Posted: August 25, 2020

Record last verified: 2021-02

Locations

US (3)