Theranostics of Radiolabeled Somatostatin Antagonists 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11 in Patients With Neuroendocrine Tumors

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02609737
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Actual Duration (Months): 60.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study has 3 steps and not everyone will have all 3 steps done. The overall goals are to see if a new experimental drug is safe to image (step 1) and treat neuroendocrine tumors (step 2 and 3).

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Tumors	Device: PET/CT Imaging; Radiation: 68Ga-DOTA-JR11; Radiation: 177Lu-DOTA-JR11	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Theranostics of Radiolabeled Somatostatin Antagonists 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11 in Patients With Neuroendocrine Tumors
• Actual Study Start Date: Nov 13, 2015
• Actual Primary Completion Date: Dec 10, 2020
• Actual Study Completion Date: Dec 10, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 68Ga-DOTA-JR11 and 177Lu-DOTA-JR11 Pts get a PET/CT study with approx.150-200 MBq of 68Ga-DOTA-JR11. Lesions with focal radiotracer uptake not explained by physiologic sstr2 expression will be interpreted as metastatic disease. If 68Ga-DOTA-JR11 uptake by metastases with a diameter of more than 2 cm is less than the physiologic radiotracer uptake by the liver, no further imaging & therapy will be performed as part of the study, as it is unlikely that pts with this low radiotracer uptake will benefit from PRRT (2). All other pts will undergo a dosimetric study with 1850 MBq (less than 100 μg peptide) of 177Lu-DOTA-JR11. Results of the dosimetry study, will determine the balance of activity of 177Lu-DOTA-JR11 that can be administered without exceeding the radiation dose limits. This activity will be split into 2 equal amounts to be delivered in 2 cycles, approximately 3 months apart. After each therapy cycle, pts will be followed clinically for 3 months.

Device: PET/CT Imaging; Radiation: 68Ga-DOTA-JR11; Radiation: 177Lu-DOTA-JR11

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [2 years]

   according to RECIST 1.1 and median progression-free and overall survival will be estimated and reported with 95% confidence intervals

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ability to understand and the willingness to sign a written informed consent document

• Adults ≥ 18 years old

• Histologically or cytologically confirmed metastatic and/or unresectable progressive, well differentiated carcinoid or pancreatic NET carcinoids

• Progressive metastatic disease defined by one of the following, occurring within 6 months of study entry:

• At least a 20% increase in radiologically or clinically measurable disease

• Appearance of any new lesion

• Symptomatic disease (including worsening hormonal symptoms or symptoms related to tumor burden)

• Measurable disease as defined by RECIST 1.1.

• At least one metastasis must show uptake of 111In-DTPA-octreotide on SPECT that is higher than the physiologic radiotracer uptake by the liver

• ECOG performance status ≤ 2 (Karnofsky ≥ 60%)

• Patients must have normal organ and marrow function as defined below:

• Leukocytes ≥ 3.0 x 109/L

• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

• Hemoglobin ≥ 9.0 g/dL

• Platelets ≥ 200 x 10^9/L

• Total bilirubin ≤ 1.25 x Upper Limit Normal (ULN)

• AST (SGOT)/ ALT(SGPT) ≤ 2.5 x ULN with liver metastases

• Alkaline phosphatase < 2 x ULN (if known liver or bone disease)

• Serum albumin > 30 g/L, or serum albumin = 30 g/L but normal prothrombin time

• Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) calculated CrCl ≥ 60 mL/min/1.73m^2

• Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

• Previous local therapy (e.g., chemoembolization or bland embolization) is allowed if completed > 6 weeks prior to study entry. For such patients, there must be either progression of measurable disease documented within the treatment field, or measurable progressive disease outside the treatment field prior to study entry.

• Previous chemotherapy and/or investigational agents are allowed if completed > 4 weeks prior to study entry (> 6 weeks if last regimen contained bis-chloroethyl nitrosourea (BCNU) or mitomycin C). For patients who received systemic therapy prior to study entry, there must be documented progression of measurable disease since receiving systemic therapy prior to study entry.

• Patients must not have disease that is currently amenable to surgery. Prior surgery is allowed no less than 6 weeks prior to study entry.

Exclusion Criteria:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-DOTA-JR11 as assessed from medical records

• Life expectancy < 6 months as assessed by the treating physician.

• Treatment with short-acting somatostatin analogs less than 3 days and Sandostatin® depot injection less than 5 weeks before scanning and treatment

• 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

• Women who are pregnant or breastfeeding

• Toxicities from prior therapies that have not resolved to grade 1 or grade 0

• Known CNS metastases and/or carcinomatous meningitis

• Active malignancy of metastatic potential other than the known carcinoid or pancreatic NET within the past three years

• 20% bone marrow external beam radiotherapy and/or previous radioisotope therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Lisa Bodei, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 9, 2020

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT02609737
• Other Study ID Numbers: 15-161
• First Posted: Nov 20, 2015
• Last Update Posted: Feb 1, 2022
• Last Verified: Dec 1, 2020

• Keywords provided by Memorial Sloan Kettering Cancer Center: Radiolabeled Somatostatin Antagonists; 68Ga-DOTA-JR11; 177Lu-DOTA-JR11; Pet scan; CT scan; 15-161
• Additional relevant MeSH terms: Neuroendocrine Tumors; 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Study Results

Participant Flow

Arm/Group Title	68Ga-DOTA-JR11 and 177Lu-DOTA-JR11
Arm/Group Description	Pts get a PET/CT study with approx.150-200 MBq of 68Ga-DOTA-JR11. Lesions with focal radiotracer uptake not explained by physiologic sstr2 expression will be interpreted as metastatic disease. If 68Ga-DOTA-JR11 uptake by metastases with a diameter of more than 2 cm is less than the physiologic radiotracer uptake by the liver, no further imaging & therapy will be performed as part of the study, as it is unlikely that pts with this low radiotracer uptake will benefit from PRRT (2). All other pts will undergo a dosimetric study with 1850 MBq (less than 100 μg peptide) of 177Lu-DOTA-JR11. Results of the dosimetry study, will determine the balance of activity of 177Lu-DOTA-JR11 that can be administered without exceeding the radiation dose limits. This activity will be split into 2 equal amounts to be delivered in 2 cycles, approximately 3 months apart. After each therapy cycle, pts will be followed clinically for 3 months.
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	68Ga-DOTA-JR11 and 177Lu-DOTA-JR11
Arm/Group Description	Pts get a PET/CT study with approx.150-200 MBq of 68Ga-DOTA-JR11. Lesions with focal radiotracer uptake not explained by physiologic sstr2 expression will be interpreted as metastatic disease. If 68Ga-DOTA-JR11 uptake by metastases with a diameter of more than 2 cm is less than the physiologic radiotracer uptake by the liver, no further imaging & therapy will be performed as part of the study, as it is unlikely that pts with this low radiotracer uptake will benefit from PRRT (2). All other pts will undergo a dosimetric study with 1850 MBq (less than 100 μg peptide) of 177Lu-DOTA-JR11. Results of the dosimetry study, will determine the balance of activity of 177Lu-DOTA-JR11 that can be administered without exceeding the radiation dose limits. This activity will be split into 2 equal amounts to be delivered in 2 cycles, approximately 3 months apart. After each therapy cycle, pts will be followed clinically for 3 months.
Overall Participants	20
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	10 50%
Male	10 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5%
Not Hispanic or Latino	19 95%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 10%
White	16 80%
More than one race	0 0%
Unknown or Not Reported	1 5%
Region of Enrollment (Count of Participants)
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	according to RECIST 1.1 and median progression-free and overall survival will be estimated and reported with 95% confidence intervals
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	68Ga-DOTA-JR11 and 177Lu-DOTA-JR11
Arm/Group Description	Pts get a PET/CT study with approx.150-200 MBq of 68Ga-DOTA-JR11. Lesions with focal radiotracer uptake not explained by physiologic sstr2 expression will be interpreted as metastatic disease. If 68Ga-DOTA-JR11 uptake by metastases with a diameter of more than 2 cm is less than the physiologic radiotracer uptake by the liver, no further imaging & therapy will be performed as part of the study, as it is unlikely that pts with this low radiotracer uptake will benefit from PRRT (2). All other pts will undergo a dosimetric study with 1850 MBq (less than 100 μg peptide) of 177Lu-DOTA-JR11. Results of the dosimetry study, will determine the balance of activity of 177Lu-DOTA-JR11 that can be administered without exceeding the radiation dose limits. This activity will be split into 2 equal amounts to be delivered in 2 cycles, approximately 3 months apart. After each therapy cycle, pts will be followed clinically for 3 months.
Measure Participants	20
Complete Response	1 5%
Partial Response	8 40%
Stable Disease	8 40%
Progression of Disease	3 15%

Adverse Events

Time Frame	1 year
Arm/Group Title	68Ga-DOTA-JR11 and 177Lu-DOTA-JR11
Arm/Group Description	Pts get a PET/CT study with approx.150-200 MBq of 68Ga-DOTA-JR11. Lesions with focal radiotracer uptake not explained by physiologic sstr2 expression will be interpreted as metastatic disease. If 68Ga-DOTA-JR11 uptake by metastases with a diameter of more than 2 cm is less than the physiologic radiotracer uptake by the liver, no further imaging & therapy will be performed as part of the study, as it is unlikely that pts with this low radiotracer uptake will benefit from PRRT (2). All other pts will undergo a dosimetric study with 1850 MBq (less than 100 μg peptide) of 177Lu-DOTA-JR11. Results of the dosimetry study, will determine the balance of activity of 177Lu-DOTA-JR11 that can be administered without exceeding the radiation dose limits. This activity will be split into 2 equal amounts to be delivered in 2 cycles, approximately 3 months apart. After each therapy cycle, pts will be followed clinically for 3 months.
All Cause Mortality
	68Ga-DOTA-JR11 and 177Lu-DOTA-JR11
	Affected / at Risk (%)	# Events
Total	11/20 (55%)
Serious Adverse Events
	68Ga-DOTA-JR11 and 177Lu-DOTA-JR11
	Affected / at Risk (%)	# Events
Total	7/20 (35%)
Blood and lymphatic system disorders
Anemia	1/20 (5%)
Cardiac disorders
Cardiac arrest	1/20 (5%)
Gastrointestinal disorders
Esophageal varices hemorrhage	2/20 (10%)
Infections and infestations
Infections and infestations - Other, specify	1/20 (5%)
Lung infection	1/20 (5%)
Investigations
Lymphocyte count decreased	5/20 (25%)
Neutrophil count decreased	3/20 (15%)
Platelet count decreased	6/20 (30%)
White blood cell decreased	3/20 (15%)
Other (Not Including Serious) Adverse Events
	68Ga-DOTA-JR11 and 177Lu-DOTA-JR11
	Affected / at Risk (%)	# Events
Total	13/20 (65%)
Gastrointestinal disorders
Diarrhea	2/20 (10%)
Mucositis (oral)	1/20 (5%)
Nausea	1/20 (5%)
Vomiting	1/20 (5%)
General disorders
Edema (face)	1/20 (5%)
Edema (limbs)	2/20 (10%)
Nervous system disorders
Asthenia	1/20 (5%)
Tremor	1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/20 (5%)
Skin and subcutaneous tissue disorders
Alopecia	2/20 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.