UPCC 36315 A Phase II Study Of Everolimus (RAD001) And Lenvatinib (E7080) In Patients With Metastatic Differentiated Thyroid Cancer Who Have Progressed on Lenvatinib Alone

NCT03139747 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: UPCC 36315
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2 Study of Everolimus and Lenvatinib in patients with metastatic differentiated thyroid cancer who have progressed on lenvatinib alone. Patient will have imaging, lab test and physical exams

Conditions

Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• Number of subjects with progression free survival

  2 years

Study Arms (1)

Single Arm

EXPERIMENTAL

Drug: Lenvatinib; Drug: Everolimus

Interventions

Lenvatinib DRUG

Lenvatinib is an anti-cancer drug for the treatment of certain kinds of thyroid cancer, and potentially for other cancers as well. It was developed by Eisai Co. and acts as a multiple kinase inhibitor against the VEGFR1, VEGFR2 and VEGFR3 kinases.

Single Arm

Everolimus DRUG

It is currently used as an immunosuppressant to prevent rejection of organ transplants and in the treatment of renal cell cancer and other tumours. Much research has also been conducted on everolimus and other mTOR inhibitors as targeted therapy for use in a number of cancers.

Single Arm

Eligibility Criteria

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

You may qualify if:

• Patients must be 18 years old or older.
• ECOG performance status \< 2 (Appendix 1).
• Patients must have histologically confirmed differentiated thyroid cancer, that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Patients may have received multiple treatments of radioactive iodine. Patients may have received one or more prior MKI treatments that are not lenvatinib (note: all patients will have been required to have had lenvatinib for entry, see below). At least 4 weeks must have elapsed since prior non-lenvatinib MKI treatment.
• Patients are eligible immediately following progression on lenvatinib. Patients must have had documented progression while on the prior treatment with lenvatinib and must have had a minimum of stable disease for 4 months.
• Measurable disease defined as at least one malignant lesion that can be accurately and serially measured in at least one dimension (longest diameter to be recorded) using conventional methods (CT, MRI, x-ray, PE) (diameter \> 20 mm) or spiral CT (diameter \> 10 mm).
• Life expectancy greater than 3 months.
• Adequate organ function that has been determined within 14 days prior to enrollment, defined as:
• Leukocyte count \> 3,000/uL; Absolute neutrophil count (ANC) \> 1,500/mm3, platelets \> 75,000/mm3, and hemoglobin \> 9 g/dl.
• Serum creatinine \< 1.5 times ULN, or 24-hour creatinine clearance \> 75 cc/min. (Note: creatinine clearance need not be determined if the baseline serum creatinine is within normal limits).
• Serum bilirubin \< 2.0mg/dL; ALT and AST \< 2.5 ULN;
• INR \< 2.0 or a PT/PTT within normal limits. Exception allowed for patients receiving anti-coagulation treatment with an agent such as warfarin or heparin who may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of lenvatinib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
• Intellectual, emotional, and physical ability to comply with oral medication.
• Ability to understand and the willingness to sign a written informed consent
• Signed informed consent obtained prior to any screening procedures.

You may not qualify if:

• Patients who have had any intervening systemic cancer treatment since the prior lenvatinib treatment.
• Patients with significant medical disease including: uncontrolled congestive heart failure; active symptoms of coronary artery disease, uncontrolled seizure disorder; active infection; uncontrolled diabetes mellitus; requirement for chronic high dose corticosteroid treatment (Topical or inhaled corticosteroids are allowed); requirement for concurrent immunosuppressive drug(s); active autoimmune disease.
• Patients with organ allografts.
• Patients with uncontrolled BP prior to the start of treatment
• Patients with known HIV-infection (HIV testing is not required for participation).
• Pregnant or nursing (lactating) women;
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after. Highly effective contraception methods include any of the following:
• Use of oral, injected or implanted hormonal methods of contraception or;
• Placement of an intrauterine device (IUD) or intrauterine system (IUS);
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;
• Total abstinence or;
• Male/female sterilization. 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 prior to randomization. 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. Male patients 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 history of second cancer (except adequately non-melanoma skin cancer, in situ treated cancer of the cervix, uterus, colon cancer or melanoma, any benign cancer for which the patient does not require treatment, or any other cancer for which the patient has been disease-free for three or more years).
• Patients who have received live attenuated vaccines within 1 week of start of Everolimus and during the study. Patient should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines;
• Patients with uncontrolled diabetes mellitus as defined by HbA1c \>8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

lenvatinib; Everolimus

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

Study Officials

• Marcia Brose, MD, PhD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: May 4, 2017
• Study Start: April 3, 2017
• Primary Completion: May 30, 2022
• Study Completion: May 30, 2022
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (1)