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NCT05773274 | RECRUITING | Metastatic Midgut Neuroendocrine Tumor

Comparing Retreatment of 177Lu-DOTATATE PRRT Versus Everolimus in Patients With Metastatic Unresectable Midgut Neuroendocrine Tumors, NET RETREAT Trial
Sponsor:

National Cancer Institute (NCI)

Brief Summary:

This phase II trial compares the effect of retreatment with 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) to the usual approach of treatment with everolimus in patients who have previously received 177Lu-DOTATATE for midgut neuroendocrine tumor (NET) that has spread from where it first started (primary site) to other places in the body (metastatic) and that cannot be removed by surgery (unresectable). PRRT is a type of radiation therapy for which a radioactive chemical is linked to a peptide (small protein) that targets cancer cells. When this radioactive peptide is injected into the body, it binds to a specific receptor found on some cancer cells. The radioactive peptide builds up in these cells and helps kill the cancer cells without harming normal cells. In this trial 177Lu-DOTATATE is used for PRRT. 177Lu-DOTATATE PRRT may increase the length of time until worsening of the midgut NET compared to the usual approach. Everolimus is in a class of medications called kinase inhibitors. It is also a type of angiogenesis inhibitor. Everolimus works by stopping cancer cells from reproducing and by decreasing blood supply to the cancer cells. Retreating with 177Lu-DOTATATE may work better than everolimus in shrinking or stabilizing tumor in patients with metastatic and unresectable NET who were previously treated with 177Lu-DOTATATE.

Condition or disease

Metastatic Midgut Neuroendocrine Tumor

Metastatic Midgut Neuroendocrine Tumor G1

Metastatic Midgut Neuroendocrine Tumor G2

Unresectable Midgut Neuroendocrine Tumor

Intervention/treatment

Biospecimen Collection

Computed Tomography

Everolimus

Lutetium Lu 177 Dotatate

Quality-of-Life Assessment

Questionnaire Administration

Phase

PHASE2

Detailed Description:

PRIMARY OBJECTIVE: I. To evaluate the effect of lutetium Lu 177 dotatate (177Lu-DOTATATE) versus (vs.) everolimus on progression-free survival (PFS) in patients with metastatic/unresectable midgut neuroendocrine tumour (NET) who have progressed following previous peptide receptor radionuclide therapy (PRRT). SECONDARY OBJECTIVES: I. To evaluate the toxicity and safety of 177Lu-DOTATATE and everolimus. II. To determine the effect of 177Lu-DOTATATE vs. everolimus on overall response rate (ORR). III. To evaluate the effect of 177Lu-DOTATATE vs. everolimus on overall survival (OS). IV. To evaluate post progression survival (PPS) and time to second objective disease progression (PFS2) for patients randomized to Arm 2 of the study and crossed over to Arm 1 at time of objective progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. V. To evaluate the effect of 177Lu-DOTATATE vs. everolimus on patient quality of life (QoL). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive 177Lu-DOTATATE intravenously (IV) every 8 weeks (Q8W). Treatment repeats for two cycles in the absence of disease progression or unacceptable toxicities. Patients also undergo computed tomography (CT) scan and collection of blood samples while on study. ARM II: Patients receive everolimus orally (PO) on a daily basis (QD). Treatment continues in the absence of disease progression or unacceptable toxicities. Patients whose cancer worsens may cross over to ARM I. Patients also undergo CT scan and collection of blood samples while on study.

Study Type : INTERVENTIONAL
Estimated Enrollment : 100 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : NET RETREAT: A Phase II Study of 177 Lutetium-DOTATATE Retreatment vs. Everolimus in Metastatic/Unresectable Midgut NET
Actual Study Start Date : 2024-01-12
Estimated Primary Completion Date : 2026-04-30
Estimated Study Completion Date : 2026-04-30

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Inclusion Criteria
  • * Patients must be at least \>= 18 years of age
  • * Metastatic, histologically confirmed grade 1 or 2 well-differentiated midgut neuroendocrine tumours, including NETs of unknown primary thought to be of midgut origin, with positive Gallium-68 DOTATATE scan or Copper-64 DOTATATE scan within the last 12 months is recommended but within the last 36 months is allowed. Lesions on Gallium-68 or Copper-64 DOTATATE scan will be considered positive if the maximum standardized uptake value (SUVmax) of target lesion is \> SUV mean of normal liver parenchyma
  • * Have received 3 or 4 cycles of PRRT using 177Lu-DOTATATE or a cumulative exposure of 22,200 MBq (600mCi) or 29,600 MBq (800 mCi) within a 52-week period. Previous therapy with everolimus for a maximum period of 1 month is permitted. No previous targeted alpha therapy is permitted. No previous alkylator therapy (i.e. Temodar) is permitted
  • * Have had radiological progression per RECIST 1.1 after prior PRRT treatment and no sooner than 12 months from last scan performed post completion of initial PRRT where either stable disease, partial response, or complete response has been maintained throughout
  • * Have not received any intervening therapy after initial PRRT
  • * No ongoing toxicity from prior PRRT that is grade 3 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0
  • * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
  • * Hemoglobin \>= 80 g/L (\>= 8.0 g/dL) (measured within 28 days prior to enrollment)
  • * Absolute neutrophil count \>= 1.0 x 10\^9/L (\>= 1000/mm\^3) (measured within 28 days prior to enrollment)
  • * Platelets \>= 80 x 10\^9/L (\>= 80 x 10\^3/mm\^3) (measured within 28 days prior to enrollment)
  • * Total bilirubin \< 1.5 x upper limit of normal (ULN) (upper limit of normal) (measured within 28 days prior to enrollment)
  • * If confirmed Gilbert's, eligible providing =\< criteria x ULN
  • * Creatinine clearance \> 50 mL/min (measured within 28 days prior to enrollment)
  • * Creatinine clearance to be measured directly by 24 hour urine sampling or as calculated by Cockcroft and Gault equation
  • * Prior or current use of somatostatin analogues is allowed for carcinoid syndrome control or in PRRT re-treatment patient population (Arm 1). Patients randomized to everolimus (Arm 2) will not be allowed to continue somatostatin analogues unless they have functional carcinoid syndrome
  • * Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
  • * Patients of childbearing potential must have agreed to use a highly effective contraceptive method during protocol treatment and for 7 months after the last dose of protocol treatment. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • * Women of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation; this may include an ultrasound to rule-out pregnancy if a false-positive is suspected. For example, when beta-human chorionic gonadotropin is high and partner is vasectomized, it may be associated with tumour production of human chorionic gonadotropin (hCG), as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy
  • * Patients must be accessible for treatment, response assessment, and follow up. Patients enrolled on this trial must be treated and followed at the participating center. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up
  • * Patients must agree to return to their primary care facility for any adverse events which may occur through the course of the trial
  • * Patient must have access to everolimus. In the event that site/investigator is unable to provide access to the drug, patient will not be eligible for this trial
  • * Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Exclusion Criteria
  • * Major surgical procedures within 6 weeks from randomization date
  • * Known brain metastases, unless these metastases have been treated, stabilized and off steroids for at least 4 weeks prior to enrollment in the study. Patients with a history of brain metastases must have a head CT and/or MRI with contrast to document stable disease prior to enrollment in the study
  • * Uncontrolled congestive heart failure no worse than New York Heart Association Class (NYHA) IIB
  • * Inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents
  • * Patients with any other significant medical or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study
  • * Pregnant women are excluded from this study because 177Lu-DOTATATE is a peptide receptor radionuclide therapy with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 177Lu-DOTATATE, breastfeeding should be discontinued if the mother is treated with everolimus or 177Lu-DOTATATE and for 2.5 months following the last treatment
Comparing Retreatment of 177Lu-DOTATATE PRRT Versus Everolimus in Patients With Metastatic Unresectable Midgut Neuroendocrine Tumors, NET RETREAT Trial

Location Details

NCT05773274

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Locations

RECRUITING

United States, Albama

University of Alabama at Birmingham Cancer Center

Birmingham, Albama, United States, 35233

RECRUITING

United States, Arizona

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, United States, 85054

RECRUITING

United States, Colorado

UCHealth University of Colorado Hospital

Aurora, Colorado, United States, 80045

RECRUITING

United States, Florida

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, United States, 33180

RECRUITING

United States, Florida

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States, 33146

RECRUITING

United States, Florida

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States, 33442

RECRUITING

United States, Florida

Mayo Clinic in Florida

Jacksonville, Florida, United States, 32224-9980

RECRUITING

United States, Florida

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States, 33136

RECRUITING

United States, Florida

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States, 33176

RECRUITING

United States, Florida

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States, 33324

RECRUITING

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

RECRUITING

United States, Illinois

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States, 60637

RECRUITING

United States, Illinois

Northwestern Medicine Cancer Center Kishwaukee

Decalb, Illinois, United States, 60115

RECRUITING

United States, Illinois

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States, 60134

RECRUITING

United States, Illinois

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, United States, 60451

RECRUITING

United States, Illinois

University of Chicago Medicine-Orland Park

Orland Park, Illinois, United States, 60462

RECRUITING

United States, Illinois

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States, 60555

RECRUITING

United States, Kentucky

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States, 40536

RECRUITING

United States, Road cancer

Henry Ford Hospital

Detroit, Road cancer, United States, 48202

RECRUITING

United States, Minnesota

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

RECRUITING

United States, New Mexico

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87106

RECRUITING

United States, New York

University of Rochester

Rochester, New York, United States, 14642

RECRUITING

United States, Ohio

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States, 43210

RECRUITING

United States, Utah

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States, 84112

RECRUITING

Canada, British Columbia

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada, V5Z 4E6

RECRUITING

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

RECRUITING

Canada, Ontario

Ottawa Hospital and Cancer Center-General Campus

Ottawa, Ontario, Canada, K1h 8l6

RECRUITING

Canada, Ontario

Odette Cancer Centre- Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, M4N 3M5