| CTRI Number |
CTRI/2021/12/038483 [Registered on: 07/12/2021] Trial Registered Prospectively |
| Last Modified On: |
19/11/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
A research study to assess the safety, effects and status of patient condition reported directly from the patient of radioactive treatment with 177Lu-Edotreotide versus standard of care in patients with Neuroendocrine cancer. |
|
Scientific Title of Study
|
A Prospective, Randomized, Controlled, Open-label, Multicenter Trial to Evaluate Efficacy, Safety and Patient-reported Outcomes of Peptide Receptor Radionuclide Therapy with Lutetium (177Lu) Edotreotide versus Standard of Care in Patients with Well-differentiated Aggressive Grade 2 and Grade 3, Somatostatin Receptor positive, Neuroendocrine Tumors of GastroEnteric or Pancreatic Origin. |
| Trial Acronym |
COMPOSE |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 2021-001086-20 |
EudraCT |
| DP-1111-02CT Protocol version 5.0 IN, dated 14/02/2025 |
Protocol Number |
| NCT04919226 |
ClinicalTrials.gov |
| US IND-136’823 |
Other |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Radhika Bobba |
| Designation |
Regional Director, India and Far East |
| Affiliation |
PSI CRO pharma India Pvt Ltd |
| Address |
PSI CRO Pharma India Pvt Ltd, 414 Shree complex, 73, St Johns Road, Bangalore, India- 560042
Bangalore
KARNATAKA
560042
India |
| Phone |
|
| Fax |
|
| Email |
Radhika.Bobba@psi-cro.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Radhika Bobba |
| Designation |
Regional Director, India and Far East |
| Affiliation |
PSI CRO pharma India Pvt Ltd |
| Address |
PSI CRO Pharma India Pvt Ltd, 414 Shree complex, 73, St Johns Road, Bangalore, India- 560042
Bangalore
KARNATAKA
560042
India |
| Phone |
|
| Fax |
|
| Email |
Radhika.Bobba@psi-cro.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Radhika Bobba |
| Designation |
Regional Director, India and Far East |
| Affiliation |
PSI CRO pharma India Pvt Ltd |
| Address |
PSI CRO Pharma India Pvt Ltd, 414 Shree complex, 73, St Johns Road, Bangalore, India- 560042
Bangalore
KARNATAKA
560042
India |
| Phone |
|
| Fax |
|
| Email |
Radhika.Bobba@psi-cro.com |
|
|
Source of Monetary or Material Support
|
| ITM Solucin GmbH, Lichtenbergstrasse 1, 85748 Garching, Germany |
|
|
Primary Sponsor
|
| Name |
ITM Solucin GmbH |
| Address |
Lichtenbergstrasse 1, 85748 Garching, Germany |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Australia
France
Germany
India
Italy
Netherlands
Spain
United Kingdom
United States of America
Sweden |
Sites of Study
Modification(s)
|
| No of Sites = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Madhavi Tripathi |
All India Institute of Medical Sciences |
Department of Nuclear Medicine, Ansari Nagar East, Gautam Nagar, New Delhi-110029, India
New Delhi
DELHI |
9811980497
madhavi.dave.97@gamil.com |
| Dr K Govinda Babu |
HCG Cancer Centre |
HCG Double Road, No- 44-45/2, 2nd Cross, Rajaram Mohan Roy Extension, Bengaluru-560027, Karnataka, India
Bangalore
KARNATAKA |
00919845072940
kgblaugh@gmail.com |
| Dr Venkatesh Rangarajan |
Tata Memorial Hospital |
Department of Nuclear Medicine and Molecular Imaging, Main Building, Basement,Room No 58, Dr.E.Borges Road, Parel,Mumbai-40012, Maharashtra, India
Mumbai
MAHARASHTRA |
00919969014183
drvrangarajan@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 3 |
| Name of Committee |
Approval Status |
| HCG Central Ethics Committee |
Approved |
| Institute Ethics Committee, All India Institute of Medical Science |
Approved |
| Institutional Ethics Committee I/II, Tata Memorial Hospital |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C7A8||Other malignant neuroendocrine tumors, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
CAPTEM, Everolimus or FOLFOX |
Patients will receive treatment according to individual risk‑benefit assessment, institutional
protocols, the local Prescribing Information, local regulations or the local guidelines |
| Intervention |
Lutetium (177Lu) Edotreotide |
Treatment with 6 cycles of 7.5 ± 0.7 GBq lutetium (177Lu) edotreotide, each containing a mass dose of 150 μg of edotreotide (DOTATOC). The prescribed treatment cycles should be administered as scheduled (Cycle 1 followed by Cycle 2 given 6 (+ 2) weeks later, then Cycles 3, 4, 5 and 6 given 8 (± 1) weeks after the previous cycle), where possible, unless disease progression occurs. Treatment may be delayed by up to a maximum of 4 weeks per cycle if required due to safety concerns. |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
90.00 Year(s) |
| Gender |
Both |
| Details |
1) Provided written informed consent.
2) Histologically confirmed diagnosis of unresectable, well-differentiated GEP-NETs, with a Ki-67 index between 15 and 55, inclusive. This should be at least confirmed by a local pathological report of a biopsy specimen of the primary tumor or metastasis, or, if unavailable, willingness to undergo current biopsy for local analysis before randomization. The biopsy should not be older than 3 years on the day of screening.
3) In the investigators opinion, eligible to receive treatment with at least one of the following: CAPTEM, everolimus or FOLFOX according to individual risk benefit assessment, institutional protocols, the local Prescribing Information, local regulations or the local guidelines.
4) At least 1 measurable site of disease per RECIST v1.1 using contrast CT/MRI. Patients who are allergic to IV contrast may be imaged without.
5) SSTR+ disease, as evidenced by locally approved 68Ga-based or 64Cu-based SSTR positron emission tomography (PET) somatostatin receptor imaging (SRI; 68Ga DOTATOC, 68Ga-DOTATATE or 64Cu-DOTATATE) within 60 days prior to randomization and as close as possible to the fluorodeoxyglucose (FDG) PET:
a. All RECIST v1.1 selected target lesions have to be SSTR+
b. All other lesions considered dominant by Investigator must also be SSTR+
7) All patients need to undergo an FDG PET scan within 60 days prior to randomization and as close as possible to the PET SRI.
a. FDG PET-positive RECIST v1.1 target lesions and all other FDG PET-positive lesions considered dominant by the Investigator have to be SSTR+
8) Patients may be treatment naïve (first-line received in COMPOSE trial) or have a maximum of one prior line of systemic therapy, including SSAs, (second-line received in COMPOSE trial).
a. Patients on any prior systemic anti-neoplastic therapy (including SSAs) must have radiological disease progression (according to RECIST v1.1) within the 4 months prior to randomization, based on the Investigator’s assessment.
b. Patients who progress on systemic first-line anti-neoplastic SSA treatment SSAs may enter the trial continuing on the same dose if required for symptom control. SSA treatment for symptoms control is not considered as a line of anti-neoplastic therapy.
9) Karnofsky performance status scale greater than or equal to 60.
|
|
| ExclusionCriteria |
| Details |
1) Known hypersensitivity to lutetium-177 (177Lu), edotreotide, DOTA, any of the comparators the comparator, or any excipient or derivative (e.g. rapamycin).
2) Known hypersensitivity to lysine, arginine, or any excipient of the nephroprotective AAS given concurrently with the lutetium (177Lu) edotreotide infusion.
3) Prior external beam radiation therapy (EBRT) to GEP-NET lesions or liver directed selective internal radiation therapy within 12 weeks before randomization
4) Prior peptide receptor radionuclide therapy (PRRT)
5) Received chemotherapy, mTOR inhibitors, vascular endothelial growth factor (VEGF) pathway inhibitors, immunotherapy, interferon, chemoembolization, bland embolization, cyclosporine A, locoregional treatment (e.g. cytoreduction surgery, radiofrequency ablation [RFA], liver directed intra-arterial intervention) or SSAs within 4 weeks prior to randomization into the trial. Patients may be treated with SSAs for symptom control, but they must have remained on the same dose of the SSA as at the time of demonstrated disease progression.
6) Any major surgery within 4 weeks prior to randomization in the trial.
7) Therapy with an investigational compound and/or medical device within 30 days or 7 half-life periods (whichever is longer) prior to randomization.
8) Patients who have received a live attenuated vaccine up to 4 weeks prior to randomization. Live attenuated vaccines should not be administered during the trial treatment and over the next 3 months after the last treatment dose.
9) Patients with known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks prior to randomization. Patients
with a history of brain metastases must have a head CT or MRI with contrast to document stable brain disease prior to randomization in the study.
10) Other known malignancies, (except non-invasive skin cancer, superficial bladder cancer and carcinoma of the cervix in situ), unless definitively treated and proven no evidence of recurrence for 3 years.
11) Serious non-malignant disease (e.g. central nervous system [CNS] diseases, psychiatric, infectious, autoimmune, metabolic or dementia), that may interfere with the objectives of the trial or with the safety or compliance of the patient, as judged by the Investigator.
12) Renal, hepatic, cardiovascular, or hematological organ dysfunction, potentially interfering with the safety of the trial treatments, as follows:
a. Renal
i. Glomerular filtration rate (GFR) <50 mL/min/1.73 m2
(Calculated by the Chronic Kidney Disease Epidemiology
[CKD-EPI] equation or
ii. Creatinine clearance < 45 mL/min calculated by the Cockcroft Gault method
iii. Renal tract obstruction
b. Hepatic
i. Total bilirubin > 3 × upper limit of normal (ULN)
ii. Albumin < 30 g/L, unless prothrombin time is within normal range
iii. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5 × ULN iv. Known ascites
c. Cardiovascular
i. Heart failure (New York Heart Association [NYHA] classification III and IV)
ii. Uncontrolled hypertension
d. Hyperkalemia (in accordance with local practice) if not adequately corrected before the study treatment starts
e. Hematopoietic
i. Platelets less than or equal to 75 × 109 /L
ii. Absolute neutrophil count (ANC) < 1.5 × 109 cells/L iii. Hemoglobin (Hb) concentration < 5.0 mmol/L (< 8.0 g/dL) f. Any other ongoing hematological or renal Grade greater than or equal to 2 toxicity or other Grade greater than or equal 3 toxicity from previous standard or investigational therapies (NCI-Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
13) Current spontaneous urinary incontinence preventing safe administration of the IMP, in the Investigator’s opinion
14) Pregnancy and breast-feeding:
a. Female patients of childbearing potential or male patients with female partners of childbearing potential, unless willing to practice full and true sexual abstinence or who are surgically/permanently sterile (hysterectomy, bilateral ovariectomy or vasectomy), or female patients whose male partners have medically successful vasectomy (provided the partner is the sole sexual partner of the female patient of childbearing potential), or who are not willing to practice highly effective contraception in combination with a barrier method of contraception (e.g. condom).
Contraception methods that are considered highly effective are:
i. Oral or non-oral (injected or implanted) non-estrogen progesterone-based hormonal method; oral, intravaginal, or transdermal combined estrogen and progesterone-based hormonal methods; and/or
ii. Intrauterine device (IUD), and/or intrauterine hormone[1]releasing system (IUS).
iii. Bilateral fallopian tubal ligation.
b. Women who are breast-feeding.
15) Patients not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders) or any other vulnerable population to that sense (e.g. persons institutionalized, incarcerated etc).
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Progression free survival (PFS), defined as the time from randomization until adequately documented Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 disease progression (based on blinded, central assessment) or death whichever occurs first |
All patients will undergo efficacy assessment by RECIST v1.1 every 12± 2 weeks through CT/MRI from the randomization date (first scan will be performed after Cycle 2 for the IMP arm) until documented disease progression. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To assess the impact of PRRT with lutetium (177Lu) edotreotide on trial patient’s HRQL and neuroendocrine functional tumor symptoms during and after therapy in comparison to best standard of care. |
Heath Related Quality of Life (HRQL) questionnaires will be completed by the patient at randomization (D0) and then every 12± 2 weeks until adequately documented disease progression. |
| To assess the safety and tolerability of PRRT with lutetium (177Lu) edotreotide in trial patients compared to control treatment options. |
Safety and tolerability based on AEs, laboratory data and vital signs will be assessed. AEs from signature of informed consent up to the patient experiencing a documented disease progression.
Vital signs – will be measured all each scheduled visits per protocol for each treatment.
|
| To assess the association of clinical/radiological outcomes with baseline characteristics, functional images and tumor gene profiling |
Association of clinical/radiological outcomes with baseline characteristics, functional images and tumor gene profiling. |
Endpoints based on RECIST v1.1,
Objective response rate (ORR), proportion of randomized patients with complete response (CR) or partial response (PR). Overall survival (OS), the time from randomization until death.
Duration of response (DoR), time from experiencing first CR or PR until the next progressive disease (PD).
Disease control rate (DCR), proportion of randomized patients with CR, PR or stable disease (SD). Duration of disease control (DDC), the time from experiencing CR, PR or SD until the next subsequent PD.
|
The timepoint to further demonstrate efficacy will include parameters of morphological and functional tumor response such as ORR and DoR, DCR and DDC, as well as OS using CT/MRI with RECIST v1.1 every 12± 2 weeks. |
|
|
Target Sample Size
|
Total Sample Size="202"
Sample Size from India="12"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
02/02/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
01/12/2021 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
Brief Summary
Modification(s)
|
The purpose of the study is to evaluate the efficacy, safety & patient-reported outcomes of peptide receptor radionuclide therapy (PRRT) with 177Lu-Edotreotide as 1st or 2nd line of treatment compared to the best standard of care in patients with well-differentiated aggressive grade 2 and grade 3, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin. |