Health Trials

Comparing Retreatment of 177Lu-DOTATATE PRRT Versus the Usual Treatment in Patients With Metastatic Unresectable Gastroenteropancreatic Neuroendocrine Tumors, NET RETREAT Trial

ConditionsMetastatic Digestive System Neuroendocrine Tumor G1Metastatic Digestive System Neuroendocrine Tumor G2Unresectable Digestive System Neuroendocrine Tumor G1Unresectable Digestive System Neuroendocrine Tumor G2
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

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, sunitinib, or cabozantinib in patients who have previously received 177Lu-DOTATATE for gastroenteropancreatic neuroendocrine tumor (GEPNET) 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 tumor cells. When this radioactive peptide is injected into the body, it binds to a specific receptor found on some tumor cells. The radioactive peptide builds up in these cells and helps kill the tumor 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 GEPNET 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 tumor cells from reproducing and by decreasing blood supply to the tumor cells. Sunitinib and cabozantinib, block certain proteins, which may help keep tumor cells from growing. They may also prevent the growth of new blood vessels that tumors need to grow. Sunitinib malate is a type of tyrosine kinase inhibitor and a type of antiangiogenesis agent. Retreating with 177Lu-DOTATATE may work better than everolimus, sunitinib or cabozantinib in shrinking or stabilizing tumors in patients with metastatic and unresectable GEPNET who were previously treated with 177Lu-DOTATATE.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must be at least >= 18 years of age

Metastatic, histologically confirmed grade 1 or 2 well-differentiated gastroenteropancreatic neuroendocrine tumours, including NETs of unknown primary thought to be of gastroenterogancreatic origin, with positive Gallium-68 DOTATATE scan, Copper-64 DOTATATE scan or octreotide 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 or octreotide scan will be considered positive if the maximum standardized uptake value (SUVmax) of target lesion is > SUV mean of normal liver parenchyma

7th Edition of the TNM Classification of Malignant Tumours

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 +/- 10% variation within a 52-week period. No previous targeted alpha therapy is permitted

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Cabozantinib

    Drug

    Given PO

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scan

  • Everolimus

    Drug

    Given PO

  • Lutetium Lu 177 Dotatate

    Drug

    Given IV

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Quality-of-Life Assessment

    Other intervention

    Ancillary studies

  • Questionnaire Administration

    Other intervention

    Ancillary studies

  • Sunitinib

    Drug

    Given PO

Treatment groups

100 Participants
are divided into 2 treatment groups
Group A: Arm I (177Lu-DOTATATE)Experimental treatment 6 interventions
Group B: Arm II (everolimus)Active comparator 8 interventions

Trial outcomes

Primary outcomes

1

Progression-free survival (PFS)

The PFS of patients of both treatment groups will be described by Kaplan-Meier method and the median PFS will be estimated using the same method. A one-sided stratified log-rank test adjusting for the stratification factor at randomization will be the primary method to compare the difference in PFS between the experimental and control treatments, at the 5% level. A stratified Cox model adjusting for duration of durable response to the initial peptide receptor radionuclide therapy (durable response \>= 24 months versus \[vs.\] \< 24 months) at randomization and with one single treatment covariate will be used to estimate the hazard ratio and associated one-sided 95% confidence interval. Sensitivity analysis adjusting for all three stratification factors at randomization will also be performed.

Time frame
From randomization to any documented evidence of tumour progression or death from any cause, assessed up to 3 years

Secondary outcomes

1

Overall survival (OS)

The OS of patients of both treatment groups will be described by Kaplan-Meier method and the median OS will be estimated using the same method. A one-sided stratified log-rank test adjusting for the stratification factor at randomization will be the primary method to compare the difference in OS between the experimental and control treatments, at the 5% level. A stratified Cox model adjusting for the stratification factor at randomization and with one single treatment covariate will be used to estimate the hazard ratio and associated one-sided 95% confidence interval.

Time frame
From randomization to death from any cause, assessed up to 3 years
2

Objective response rate (ORR)

Defined as the proportion of patients with a documented complete response and partial response based on Response Evaluation Criteria in Solid Tumors 1.1. The primary estimate of ORR will be based on all patients randomized. A Cochran-Mantel-Haenszel test adjusting for the duration of durable response to the initial peptide receptor radionuclide therapy (durable response \>= 24 months vs. \< 24 months) at the time of randomization will be used to compare the objective response rates between two arms and sensitivity analysis adjusting for all three stratification factors at randomization will also be performed.

Time frame
Up to 3 years
3

Post progression survival (PPS)

Median PPS and associated two-sided 90% confidence interval will be estimated using the Kaplan-Meier method.

Time frame
From objective progression on everolimus to objective progression or death from any cause after cross-over to receive 177Lu-DOTATATE, assessed up to 3 years
4

Time to second objective disease progression (PFS2)

Median PFS2 and associated two-sided 90% confidence interval will be estimated using the Kaplan-Meier method.

Time frame
From randomization to objective tumor progression or death from any cause after the cross-over, assessed up to 3 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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