Optimizing the Interval Between Cycles of PRRT With 177lu-dotatate in sstr2 Positive Tumors

Study Overview
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Brief Summary
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Randomized Phase II Trial in sstr2 Positive Tumors to Optimize the Interval Between Cycles of PRRT With 177lu-dotatate

Detailed Description
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The main objective of this randomized phase II comparative study is to evaluate the Progression Free survival (PFS) and the safety as co-primary objective of two different schedule of administrations of 177lu-dotatate: intensive (every 5 weeks) vs no intensive (every 8-10 weeks) The secondary objectives are DCR, the late toxicity, OS and dosimetry. Patients with any tumor histotype documented as sst2-positive in pre-study period will be enrolled in the study. The study will include a total of 618 planned patients. They will be randomly assigned to receive 5 cycles of PRRT at intervals of 5 or 8-10 weeks between cycles.

Official Title
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Randomized Phase II Trial in sstr2 Positive Tumors to Optimize the Interval Between Cycles of PRRT With 177lu-dotatate

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Drug: PRRT every 5 weeks
* Drug: PRRT every 8-10 weeks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years. Patients must have histologically or cytologically confirmation of neuroendocrine tumors or any other tumor histotype documented as sst2-positive), that may benefit from receptor radionuclide therapy and for which there aren't any other effective treatments. For cerebral sst2-positive tumors, if biopsy is no feasible for technical reason or risk benefit balance, patients may be enrolled if CT or MRI strongly suggest oncological lesion confirming the 68Ga PET-CT dota-peptide SSTr2 positivity.. Measurable disease according to RECIST 1.1.criteria also patients without measurable but with evaluable disease disease can be enrolled. Any disease stage is allowed. Patients with documented disease will be admitted to therapeutic phase only if the diagnostic OctreoScan (the tumour uptake will be evaluated with a 3-grade scale, where 1 = liver uptake, 2 > liver uptake and < kidney uptake and 3 > kidney uptake: only tumour uptakes grade 2 and 3 will be considered for therapy) and/or Positron Emission Tomography (PET)/CT 68Ga-peptide images demonstrate a significant uptake in the tumour. Patients with progressive disease in pre-study period (PD within the last 12 months), refractory to conventional standard treatments; clinical progression is allowed Patients with or without concurrent therapy with somatostatin analogs Life expectancy of greater than 6 months. Eastern Cooperative Oncology Group (ECOG) performance status <2 Adequate haematological, liver and renal function: haemoglobin >= 9 g/dL, absolute neutrophil count (ANC) >= 1.5 x 109 /L, platelets >= 100 x 109 /L, bilirubin ≤1.5 X upper normal limit (UNL) , alanine aminotransferase ( ALT) and Aspartate aminotransferase (AST) <2.5 X UNL (< 5 X UNL in presence of liver metastases, creatinine < 2 mg/dL. If female of childbearing potential highly effective birth control methods, according to guideline Recommendation related to contraception and pregnancy testing in clinical trials, (2014_09_15 section 4.1) are mandatory. Participant is willing and able to give informed consent for participation in the study. Exclusion Criteria: Patients treated with chemotherapy and therapeutic radiotherapy within 4 weeks and treated within 2 weeks with palliative radiotherapy, hormonal or biological therapy. Patients treated with previous radio-metabolic therapy with an adsorbed dose to the kidney more than 23 Gy and more than 1.8 Gy for the bone marrow or as surrogate of dosimetry (13). All acute toxic effects of any prior therapy (including surgery radiation therapy, chemotherapy) must have resolved to a grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE) ECOG performance status >2 Participation in another clinical trial with any investigational agents within 30 days prior to study screening. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Assessed bone marrow invasion > 50% (with Bone Marrow biopsy or instrumental exams i.e bone scan or CT or MRI) Pregnant or breastfeeding women are excluded from the present study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: comparative
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A, Intensive<br>Arm A, Intensive every 5 weeks | Drug: PRRT every 5 weeks<br>* PRRT (radiolabelled somatostatin analogues) every 5 weeks for 5 cycles<br>|
| Experimental: Arm B, Non Intensive<br>Arm B, Non Intensive every 8-10 weeks | Drug: PRRT every 8-10 weeks<br>* PRRT (radiolabelled somatostatin analogues) every 8-10 weeks for 5 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression free survival is defined as the time from the randomization date to the date of first observation of documented disease progression or death due to any cause | up to 5 years | 
| Incidence of Treatment-Emergent Adverse Events | The evaluation of Treatment-Emergent Adverse Events, defined as any G3/G4 toxicity from 1st treatment cycle until 30 days after the last treatment cycle will be based on version 4.0 CTC-AE | up to 30 days after last treatment cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DCR | Disease Control Rate (DCR) is defined as the percentage of patients who have achieved complete response, partial response and stable disease for at least 12 weeks from therapy start. DCR will be evaluated using the new international criteria proposed by the Version 1.1 Response Evaluation Criteria in Solid Tumors (RECIST) | up to 5 years | 
| OS | Overall Survival (OS) is defined as the time from treatment start to the time of death due to any cause or the date of last contact (censored observation) at the date of data cut-off. | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sst2-positive tumors, Neuroendocrine Tumors, radiolabelled somatostatin analogues (PRRT)