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177Lutethium - Peptide Receptor Radionuclide Therapy (Lu-PRRT) Plus Capecitabine Versus Lu-PRRT in FDG Positive, Gastro-entero-pancreatic Neuroendocrine Tumors (Lu-Ca-S)

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ClinicalTrials.gov Identifier: NCT02736448
Recruitment Status : Recruiting
First Posted : April 13, 2016
Last Update Posted : February 27, 2019
Sponsor:
Information provided by (Responsible Party):
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Tracking Information
First Submitted Date  ICMJE April 7, 2016
First Posted Date  ICMJE April 13, 2016
Last Update Posted Date February 27, 2019
Study Start Date  ICMJE May 2016
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2016)
Progression free survival [ Time Frame: up to 72 months ]
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. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02736448 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 26, 2019)
  • Disease control rate [ Time Frame: up to 72 months ]
    DCR will be evaluated using the new international criteria proposed by the Version 1.1 Response Evaluation Criteria in Solid Tumors (RECIST).
  • toxicity [ Time Frame: up to 72 months ]
    The acute toxicity is the toxicity that occurred within 30 days from the last treatment administration. The late toxicity is the toxicity that occurred over 30 days from the last treatment administration. NCI-CTCAE v. 4.03 will be applied and a profile of adverse events related to the study drug will be described.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2016)
  • Disease control rate [ Time Frame: up to 72 months ]
    DCR will be evaluated using the new international criteria proposed by the Version 1.1 Response Evaluation Criteria in Solid Tumors (RECIST).
  • toxicity [ Time Frame: up to 72 months ]
    The acute toxicity is the toxicity that occurred within 30 days from the last treatment administration. The late toxicity is the toxicity that occurred over 30 days from the last treatment administration. NCI-CTCAE v. 4.03 will be applied
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 177Lutethium - Peptide Receptor Radionuclide Therapy (Lu-PRRT) Plus Capecitabine Versus Lu-PRRT in FDG Positive, Gastro-entero-pancreatic Neuroendocrine Tumors
Official Title  ICMJE 177Lutethium - Peptide Receptor Radionuclide Therapy (Lu-PRRT) Plus Capecitabine Versus Lu-PRRT in FDG Positive, Gastro-entero-pancreatic Neuroendocrine Tumors: a Randomized Phase II Study.
Brief Summary

This is a randomized phase II, parallel group study. Patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) well differentiated G1 - G2 (ki67≤ 20%) and G3 (ki67≤ 50%), somatostatin receptor (SSR) positive and 18-FDG positive will be enrolled in the study and will be randomly assigned to 2 different arms:

  • Arm Lu-PRRT-Cap: oral low dose of capecitabine in association with Lu-PRRT (at 3.7 Gbq per cycle x 7 cycles) followed by long acting octreotide or lanreotide (SS-LAR); OR
  • Arm Lu-PRRT: Lu-PRRT (at 3.7 gigabecquerel (Gbq) per cycle x 7 cycles) followed by SS-LAR.
Detailed Description

This is a randomized phase II, parallel group study. Patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) well differentiated G1 - G2 (ki67≤ 20%) and G3 (ki67≤ 50%), SSR positive and 18-fluorodeoxyglucose (FDG) positive will be enrolled in the study and will be randomly assigned to 2 different arms:

  • Arm Lu-PRRT-Cap: oral low dose of capecitabine in association with Lu-PRRT (at 3.7 Gbq per cycle x 7 cycles) followed by long acting octreotide or lanreotide (SS-LAR); OR
  • Arm Lu-PRRT: Lu-PRRT (at 3.7Gbq per cycle x 7 cycles) followed by SS-LAR. The primary objective is to evaluate the progression free survival (PFS) in the two arms.

The secondary objectives are: i) the efficacy (disease control rate, DCR), ii) acute and late toxicity, and iii) overall survival (OS).

The investigators plan to enroll 176 patients during a period of 36 months and a period of 36 months of follow up

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gastro-entero-pancreatic Neuroendocrine Tumors
Intervention  ICMJE
  • Drug: Capecitabine
    oral low dose of capecitabine
  • Drug: Lu-PRRT
    Lu-PRRT (at 3.7Gbq per cycle x 7 cycles)
  • Drug: SS-LAR
    long acting octreotide or lanreotide
Study Arms  ICMJE
  • Experimental: Arm Lu-PRRT-Cap
    Arm Lu-PRRT-Cap: oral low dose of capecitabine in association with Lu-PRRT (at 3.7 Gbq per cycle x 7 cycles) followed by long acting octreotide or lanreotide (SS-LAR)
    Interventions:
    • Drug: Capecitabine
    • Drug: Lu-PRRT
    • Drug: SS-LAR
  • Experimental: Arm Lu-PRRT
    Arm Lu-PRRT: Lu-PRRT (at 3.7Gbq per cycle x 7 cycles) followed by long acting octreotide or lanreotide (SS-LAR)
    Interventions:
    • Drug: Lu-PRRT
    • Drug: SS-LAR
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 12, 2016)
176
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2021
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histopathologic diagnosis of gastro-entero-pancreatic neuroendocrine tumor, well differentiated G1 - G2 (ki67≤20%) and G3 (ki67≤50%)
  2. Male or Female, aged >18 years
  3. Measurable disease according to RECIST 1.1 criteria
  4. Patients with documented disease will be admitted to therapeutic phase only if the diagnostic receptor imaging, OctreoScan, with a significant uptake in the tumor (grade 2 or 3, according to Rotterdam scale) and/or PET/CT 68Gallium (68Ga)-peptide images with a tumor uptake at least equal to liver background
  5. Patients with documented disease will be admitted to therapeutic phase only if the 18FDG PET/CT is positive with a standardized uptake value (SUV) > 2.5 at least in one documented lesion.
  6. Non operable advanced disease
  7. Documented progression after standard therapy such as long acting octreotide or lanreotide (SS-LAR), Everolimus in P-NETs or platinum based therapy in G3 patients.
  8. Patients have to finish prior standard chemotherapy or therapeutical radiotherapy (less then 25% body surface) at least 6 weeks
  9. Life expectancy greater than 6 months.
  10. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  11. Adequate haematological, liver and renal function: haemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, total bilirubin ≤ 2.5 X upper normal limit (UNL) , Alanine transaminase (ALT) <2.5 X UNL (< 5 X UNL in presence of liver metastases), creatinine < 2 mg/dL.
  12. Concomitant SS-sub-cutaneous assumption is allowed in case of carcinoid syndrome
  13. 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) (See Appendix H) are mandatory. Highly effective birth control methods are required beginning at the screening visit and continuing until 6 months following last treatment with study drug. Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment. Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 6 months after final study drug administration. Two acceptable methods of birth control thus include Condom (barrier method of contraception) and one of the following is required (established use of oral, or injected or implanted hormonal method of contraception by the female partner; placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; additional barrier method like occlusive cap with spermicidal foam/gel/film/cream/suppository in the female partner; tubal ligation in the female partner; vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), for more than 6 months.
  14. Participant is willing and able to give informed consent for participation in the study.
  15. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.

Exclusion Criteria:

  1. Ki 67 index > 50%
  2. FDG PET negative
  3. Patients treated with chemotherapy and therapeutic radiotherapy within 6 weeks
  4. More then 25% body surface radiotherapy
  5. Patients treated with previous radiometabolic therapy with an adsorbed dose to the kidney more than 23 Gy and 1,2 Gy for the bone marrow or as surrogate of dosimetry, a Total Cumulative Activity (TCA) of >250 millicurie (mCi) of 90Y dotatoc or >800 (mCi) of 177Lutethium (177Lu) dotatate
  6. 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)
  7. Life expectancy minor than 6 months.
  8. ECOG performance status >2
  9. Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
  10. 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.
  11. History of allergic reactions attributed to compounds of similar chemical or biologic composition
  12. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
  13. Known hypersensitivity to Octreotide and/or Lanreotide, and/or somatostatin correlate peptides
  14. Known hypersensitivity to capecitabine or to any of its components
  15. Known hypersensitivity to 5 - fluorouracil.
  16. Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix);
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Giovanni Paganelli, MD +390543739100 giovanni.paganelli@irst.emr.it
Contact: Oriana Nanni, PhD +390543739100 oriana.nanni@irst.emr.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02736448
Other Study ID Numbers  ICMJE IRST100.17
2014-003067-38 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Study Sponsor  ICMJE Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Giovanni Paganelli, MD IRST IRCCS, Meldola (FC)
PRS Account Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP