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Trial record 7 of 2784 for:    Neoplasms, Germ Cell and Embryonal | Neuroendocrine Tumors

Capecitabine ON Temozolomide Radionuclide Therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study (CONTROL NETS)

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ClinicalTrials.gov Identifier: NCT02358356
Recruitment Status : Recruiting
First Posted : February 9, 2015
Last Update Posted : November 22, 2017
Sponsor:
Information provided by (Responsible Party):
Australasian Gastro-Intestinal Trials Group

Brief Summary:
Two parallel phase II randomized open label trials of Lutetium-177 Octreotate (177Lu‐Octreotate) peptide receptor radionuclide therapy (PRRT) and capecitabine (CAP)/temozolomide (TEM) chemotherapy (chemo): (i) versus CAPTEM alone in the treatment of low to intermediate grade pancreatic neuroendocrine tumours (pNETs); (ii) versus PRRT alone in the treatment of low to intermediate grade mid gut neuroendocrine tumours (mNETs).

Condition or disease Intervention/treatment Phase
Midgut Neuroendocrine Tumours Pancreatic Neuroendocrine Tumours Drug: octreotate Drug: Capecitabine Drug: Temozolomide Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Capecitabine ON Temozolomide Radionuclide Therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study
Study Start Date : November 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Active Comparator: PRRT
7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 1 every 8 weeks for 4 cycles.
Drug: octreotate
7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV)
Other Name: lutate

Active Comparator: CAPTEM
Oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 every 28 day cycle, up to 8 cycles.
Drug: Capecitabine
oral capecitabine 750mg/m2 b.i.d.
Other Name: Xeloda

Drug: Temozolomide
temozolomide 75mg/m2 b.i.d.

Experimental: PRRT/CAPTEM
7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 up to 4 cycles.
Drug: octreotate
7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV)
Other Name: lutate

Drug: Capecitabine
oral capecitabine 750mg/m2 b.i.d.
Other Name: Xeloda

Drug: Temozolomide
temozolomide 75mg/m2 b.i.d.




Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 12 months for pNETs and 24 months for mNets ]
    To determine the rate of progression free survival (PFS) at 12 months in pNETs (Group A), and at 24 months in mNETs (Group B). (PFS defined from time of randomisation to disease progression as defined by RECIST criteria version 1.1).


Secondary Outcome Measures :
  1. Objective tumour response rate (partial or complete response) as per RECIST v1.1 criteria [ Time Frame: 12 months or 24 months as appropriate ]
    To determine objective tumour response rate (OTRR) (partial or complete response (PR/CR)).

  2. Overall survival (death from any cause) [ Time Frame: 12 months or 24 months as appropriate ]
    To determine overall survival (OS) (death from any cause).

  3. Safety (rates of adverse events worst grade according to NCI CTCAE v4.0) [ Time Frame: 12 months or 24 months as appropriate ]
    To determine safety (rates of adverse events).

  4. Quality of life (QOL scores determined at beginning, during treatment and until disease progression) [ Time Frame: 12 months or 24 months as appropriate ]
    To determine Quality of Life (QoL) (QoL scores from EORTC QLQ C30 and QLQ-GINET21 questionnaires)

  5. Resource utilisation (use of healthcare resources) and cost-effectiveness (Health utility score determined at beginning, during treatment and until end of follow up, correlated with MBS & PBS data) [ Time Frame: 12 months or 24 months as appropriate ]
    To determine resource utilization (costs associated with treatment regimen, MBS and PBS data, and health utilities scores from EQ-5D-5L).

  6. Clinical Benefit [ Time Frame: 12 months or 24 months as appropriate ]
    To evaluate the proportion of patients who have experienced a clinical benefit of the regimen(s). (Clinical Benefit is defined as the proportion of patients who experience complete or partial response (using RECIST v1.1) or stable disease at 12 months or 24 months as appropriate).


Other Outcome Measures:
  1. biomarkers CgA, Ki-67 and tumour MGMT expression with survival, response and safety. [ Time Frame: 12 months or 24 months as appropriate ]
    To correlate circulating & tissue biomarkers with clinical study endpoints (relating to survival, response and safety), including but not limited to CgA, Ki-67 & tumour MGMT expression.

  2. Other measures of response such as 68Ga-DOTATATE, SUVmax, tumour update and other measures of response of a biochemical measure such as tumour markers, chomogranin A and patient reported outcomes. [ Time Frame: 12 months or 24 months as appropriate ]
    Explore correlation between other measures of response relevant to this disease, eg 68Ga-DOTATATE, SUVmax tumour uptake, and other measures of response of a biochemical measure, eg. tumour markers, chromogranin A, and patient reported outcomes QOL undertaken in order to identify how progressive symptoms or biochemical response relates to conventional measures of response using structural and/or functional imaging. A formal statistical analysis plan will be formulated prior to final data analysis.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults ≥18 years old with histologically proven, moderate to well‐differentiated G1/2 pancreatic or midgut NETs with Ki‐67 < 20%;
  • The presence of somatostatin receptor avidity suitable for PRRT demonstrated on 68Ga‐octreotate PET scan;
  • Progressive advanced/metastatic disease that has progressed during or after ≤ 2 prior systemic therapies;
  • Unresectable disease, determined by an appropriately specialized surgeon or deemed not suitable for liver directed therapies where liver is the only site of disease;
  • ECOG performance status 0‐2;
  • Ability to swallow oral medication;
  • Adequate renal function (measured creatinine clearance > 50 ml/min by DTPA or 51CR-EDTA), bone marrow function (Hb > 9 g/d/L, ANC > 1.5 x109L, and platelets > 100 x 10/L);
  • Adequate liver function (serum total bilirubin ≤ 1.5 x ULN, and Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver metastases)). INR ≤ 1.5 (or on a stable dose of LMW heparin for >2 weeks at time of enrolment .);
  • Life expectancy of at least 9 months;
  • Study treatment both planned and able to start within 28 days of randomisation; )
  • Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
  • Signed, written informed consent.

Exclusion Criteria:

  • Primary NETs other than small bowel (midgut) or pancreatic NETs;
  • Cytotoxic chemotherapy, targeted therapy, or biotherapy within the last four weeks;
  • Prior intrahepatic 90Y microspheres, such as SIR-Spheres in the past six months;
  • Prior Peptide Receptor Radionuclide Therapy;
  • Major surgery/surgical therapy for any cause within one month;
  • Surgical therapy of loco-regional metastases within the last three months prior to randomisation;
  • Uncontrolled metastatic disease to the central nervous system. To be eligible, CNS metastases should have been treated with surgery and/or radiotherapy and the patient should have been receiving a stable dose of steroids for at least 2 weeks prior to randomisation, with no deterioration in neurological symptoms during this time;
  • Poorly controlled concurrent medical illness. E.g. unstable diabetes (Note: optimal glycaemic control should be achieved before starting trial therapy); Symptomatic NYHA class III or IV congestive cardiac failure, myocardial infarction within 6 months of start of the study, serious uncontrolled cardiac arrhythmia, unstable angina, or any other clinically significant cardiac disease;
  • History of other malignancies within 5 years except where treated with curative intent AND with no current evidence of disease AND considered not to be at risk of future recurrence Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible;
  • Any uncontrolled known active infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated. Participants with known Hepatitis B/C infection will be allowed to participate providing evidence of viral suppression has been documented and the patient remains on appropriate anti-viral therapy;
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of capecitabine/temozolomide (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or substantial small bowel resection);
  • Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse;
  • Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception .

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02358356


Contacts
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Contact: NHMRC CTC +61 (0) 2 9562 5000 controlnets@ctc.usyd.edu.au

Locations
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Australia, New South Wales
Royal North Shore Hospital Recruiting
St Leonards, New South Wales, Australia, 2065
Contact: Kathryn Jenkins       Kathryn.Jenkins@health.nsw.gov.au   
Principal Investigator: Nick Pavlakis         
Australia, Queensland
Royal Brisbane and Women's Hospital Recruiting
Herston, Queensland, Australia, 4029
Contact: Jenny Campbell       Jenny.Campbell@health.qld.gov.au   
Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
East Melbourne, Victoria, Australia, 8006
Contact: Elizabeth Drummond       Elizabeth.Drummond@petermac.org   
Australia, Western Australia
Fiona Stanley Hospital Recruiting
Murdoch, Western Australia, Australia, 6150
Contact: Kanako Ohara       kanako.ohara@health.wa.gov.au   
Principal Investigator: David Ransom         
Sponsors and Collaborators
Australasian Gastro-Intestinal Trials Group
Investigators
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Study Chair: Nick Pavlakis, Associate Professor Royal North Shore Hospital

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Responsible Party: Australasian Gastro-Intestinal Trials Group
ClinicalTrials.gov Identifier: NCT02358356     History of Changes
Other Study ID Numbers: CTC0120 / AG0114NET
First Posted: February 9, 2015    Key Record Dates
Last Update Posted: November 22, 2017
Last Verified: November 2017
Keywords provided by Australasian Gastro-Intestinal Trials Group:
midgut
pancreatic
neuroendocrine
advanced
unresectable low
intermediate grade
mNETs
pNETs
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Capecitabine
Temozolomide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents