Back to resultsA Dose Finding Study of CycloSam® Combined With External Beam Radiotherapy
Primary Purpose
Osteosarcoma, Bone Metastases
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
153Sm-DOTMP
External beam radiotherapy.
Calcium Carbonate
Mozobil
Neupogen Injectable Product
Sponsored by
About this trial
This is an interventional treatment trial for Osteosarcoma focused on measuring dosimetry, radiopharmaceutical, radiotherapy, Maximally tolerated dose, MTD, tumor, myelosuppression
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed diagnosis of a solid tumor metastatic to bone, or a histologically confirmed diagnosis of osteosarcoma with either an unresectable primary tumor or metastases (including tumors with an intralesional resection).
- Measurable disease on anatomic imaging that is also avid for phosphonate compounds as demonstrated by a positive 99mTc diphosphonate bone scan.
- Adequate renal function, defined as a measured creatinine clearance >70 ml/min/1.73 m2 or normal radioisotope glomerular filtration rate (GFR).
- Adequate hematologic function, defined as a platelet count > 50,000 cells/mm3 and an absolute neutrophil count (ANC) > 500 cells/mm3
- Life expectancy of at least 8 weeks.
- Karnofsky performance status > 50%
- Subject must have adequately recovered from the effects of any prior chemotherapy, as determined by the treating physician and study team, based in part on organ function defined above. Toxicities from previous therapies must have recovered to Common Terminology Criteria for Adverse Events (CTCAE) 4.0 grade 2 or better.
- Patients must have previously received effective treatment for their underlying disease and have no potentially curative options available.
Exclusion Criteria:
- Subject has received prior radiotherapy to all known areas of current active disease or has a known contraindication to receiving radiotherapy.
- Subject is pregnant or breastfeeding.
- Patient is sexually active and does not agree to use accepted, effective forms of contraception.
Sites / Locations
- Montefiore Medical Center-Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose Escalation Arm
Arm Description
Dose Levels 1-3 will consist of treatment with radiopharmaceutical (153Sm-DOTMP) alone. If the maximally tolerated dose (MTD) has not been reached at Level 3, external beam radiotherapy will be added to each of Levels 4-6. Participants enrolled on Dose Levels 4-6 will be treated with external beam radiotherapy to all radiographically evident sites of disease. If an MTD has not been determined at Level 6, the study will end and Dose Level 6 will be declared the Recommended Phase 2 Dose. Participants will be given prophylactic / supportive treatment protocols including Calcium Carbonate, mozobil, and neupogen injectable product.
Outcomes
Primary Outcome Measures
Maximally Tolerated Dose
The maximally tolerated dose (MTD) of 153Sm-DOTMP will be determined. The MTD will be defined as the dose that produces a dose limiting toxicity (DLT) in 30% of the participants. The dose limiting toxicity is the dosage at which side effects are serious enough to prevent an increase in dose or level of that treatment. DLTs will be defined as any grade 3, 4, or 5 non-hematologic toxicity experienced during a 42-70 day observation window.
Secondary Outcome Measures
Overall Survival
The overall survival of participants with bone metastatic osteosarcoma will be determined. Overall survival is defined as the time from enrollment in the study until death. Observation begins at study enrollment and terminates upon death of the subject.
Time To Progression
The time to progression of participants with bone metastatic osteosarcoma will be determined. Time to progression is defined as the time from study enrollment until the first radiographic evidence of progressive disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST). RECIST is a set of published rules that help define whether cancer patients improve, stay the same, or get worse with treatment. This study uses the revised RECIST 1.1 guidelines.
Clinical Response Rate 30 days post treatment
Participants will undergo radiographic evaluation 30 days after completion of all protocol therapy. The response of each tumor to treatment will be determined based on RECIST 1.1 criteria. Clinical response will be defined as either stable disease or a decrease in the size of the tumor by radiographic imaging (which may include CT or MRI) using RECIST 1.1 criteria.
Clinical Response Rate 4 months post treatment
Participants will undergo radiographic evaluation 4 months after completion of all protocol therapy. The response of each tumor to treatment will be determined based on RECIST 1.1 criteria. Clinical response will be defined as either stable disease or a decrease in the size of the tumor by radiographic imaging (which may include CT or MRI) using RECIST 1.1 criteria.
Clinical Response Rate 8 months post treatment
Participants will undergo radiographic evaluation 8 months after completion of all protocol therapy. The response of each tumor to treatment will be determined based on RECIST 1.1 criteria. Clinical response will be defined as either stable disease or a decrease in the size of the tumor by radiographic imaging (which may include CT or MRI) using RECIST 1.1 criteria
Clinical Response Rate 12 months post treatment
Participants will undergo radiographic evaluation 12 months after completion of all protocol therapy. The response of each tumor to treatment will be determined based on RECIST 1.1 criteria. Clinical response will be defined as either stable disease or a decrease in the size of the tumor by radiographic imaging (which may include CT or MRI) using RECIST 1.1 criteria.
Full Information
NCT ID
NCT03612466
First Posted
July 30, 2018
Last Updated
October 13, 2022
Sponsor
Albert Einstein College of Medicine
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03612466
Brief Title
A Dose Finding Study of CycloSam® Combined With External Beam Radiotherapy
Official Title
A Dose Finding Study of CycloSam® (153Sm-DOTMP) Combined With External Beam Radiotherapy to Treat High Risk Osteosarcoma and Other Solid Tumors Metastatic to Bone
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Study withdrawn before any participants could be enrolled. Issues being able to effectively recruit participants into the study.
Study Start Date
August 2022 (Anticipated)
Primary Completion Date
January 2023 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Albert Einstein College of Medicine
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a dose finding study of a novel radiopharmaceutical agent, 153Sm-DOTMP. It will be studied alone and then in combination with external beam radiotherapy. The study design includes six cohorts, Levels 1-6. The first three cohorts of participants will receive 153Sm-DOTMP alone, and if this is determined to be safe, subsequent cohorts will receive the radiopharmaceutical followed by external beam radiotherapy.
Detailed Description
This is a dose escalation study of a new radiopharmaceutical agent, 153Sm-DOTMP. Eligible participants will have osteosarcoma metastatic to bone, other solid tumors with bone metastases, or an unresectable localized osteosarcoma. Because of anticipated prolonged myelosuppression, participants will have a peripheral blood stem cell harvest. They will then be treated with 2 doses of 153Sm-DOTMP given 7 days apart. Twenty-four days after the initial dose, stem cells will be reinfused if needed. The first three cohorts of participants will receive only radiopharmaceutical. If Dose Level 3 is not the maximally tolerated dose (MTD), subsequent dose levels will include external beam radiotherapy, administered beginning on Day 15. The dose of external beam radiotherapy will be determined by dosimetry studies performed after each administration of study agent, and will be targeted to a tumoricidal dose of radiation. All participants will have disease re-evaluation 30 days following completion of all study treatments, and then at 4, 6, 8, and 12 months, unless they experience disease progression.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteosarcoma, Bone Metastases
Keywords
dosimetry, radiopharmaceutical, radiotherapy, Maximally tolerated dose, MTD, tumor, myelosuppression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation Arm
Arm Type
Experimental
Arm Description
Dose Levels 1-3 will consist of treatment with radiopharmaceutical (153Sm-DOTMP) alone. If the maximally tolerated dose (MTD) has not been reached at Level 3, external beam radiotherapy will be added to each of Levels 4-6. Participants enrolled on Dose Levels 4-6 will be treated with external beam radiotherapy to all radiographically evident sites of disease. If an MTD has not been determined at Level 6, the study will end and Dose Level 6 will be declared the Recommended Phase 2 Dose.
Participants will be given prophylactic / supportive treatment protocols including Calcium Carbonate, mozobil, and neupogen injectable product.
Intervention Type
Drug
Intervention Name(s)
153Sm-DOTMP
Other Intervention Name(s)
CycloSam
Intervention Description
For Levels 1- 3, the Day 1 dosages will be the same (0.5 millicurie (mCi)/kg 153Sm-DOTMP) for all levels but the Day 8 dosages will be 0.5, 1.0 and 3.0 mCi/kg respectively. For Levels 4, 5 & 6, the Day 1 dosages will be the same (0.5 mCi/kg 153Sm-DOTMP) for all levels but the Day 8 dosages will be 3, 6, then 10 mCi/kg 153Sm-DOTMP respectively.
Intervention Type
Radiation
Intervention Name(s)
External beam radiotherapy.
Intervention Description
The amount of radiation will be determined based on how much radiation was delivered to each tumor by the 153Sm-DOTMP, and will be targeted to 70 Gray (Gy)
Intervention Type
Drug
Intervention Name(s)
Calcium Carbonate
Intervention Description
Calcium carbonate will be given to participants as prophylaxis against hypocalcemia..
Intervention Type
Drug
Intervention Name(s)
Mozobil
Other Intervention Name(s)
plerixafor
Intervention Description
Participants who require stem cell collection will be given Mozobil to help mobilize hematopoietic stem cells into the circulation for collection.
Intervention Type
Drug
Intervention Name(s)
Neupogen Injectable Product
Other Intervention Name(s)
filgrastim
Intervention Description
Participants who require stem cell collection will be given Neupogen to help mobilize hematopoietic stem cells into the circulation for collection.
Primary Outcome Measure Information:
Title
Maximally Tolerated Dose
Description
The maximally tolerated dose (MTD) of 153Sm-DOTMP will be determined. The MTD will be defined as the dose that produces a dose limiting toxicity (DLT) in 30% of the participants. The dose limiting toxicity is the dosage at which side effects are serious enough to prevent an increase in dose or level of that treatment. DLTs will be defined as any grade 3, 4, or 5 non-hematologic toxicity experienced during a 42-70 day observation window.
Time Frame
MTD will be determined based on DLTs experienced by participants during the first 42 days after administration of 153Sm-DOTMP for Dose Levels 1-3 and during the first 70 days after administration for Dose Levels 4-6
Secondary Outcome Measure Information:
Title
Overall Survival
Description
The overall survival of participants with bone metastatic osteosarcoma will be determined. Overall survival is defined as the time from enrollment in the study until death. Observation begins at study enrollment and terminates upon death of the subject.
Time Frame
From date of enrollment until date of death from any cause, assessed up to 60 months
Title
Time To Progression
Description
The time to progression of participants with bone metastatic osteosarcoma will be determined. Time to progression is defined as the time from study enrollment until the first radiographic evidence of progressive disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST). RECIST is a set of published rules that help define whether cancer patients improve, stay the same, or get worse with treatment. This study uses the revised RECIST 1.1 guidelines.
Time Frame
Participants will be evaluated 4, 8, and 12 months after treatment.
Title
Clinical Response Rate 30 days post treatment
Description
Participants will undergo radiographic evaluation 30 days after completion of all protocol therapy. The response of each tumor to treatment will be determined based on RECIST 1.1 criteria. Clinical response will be defined as either stable disease or a decrease in the size of the tumor by radiographic imaging (which may include CT or MRI) using RECIST 1.1 criteria.
Time Frame
30 days post treatment
Title
Clinical Response Rate 4 months post treatment
Description
Participants will undergo radiographic evaluation 4 months after completion of all protocol therapy. The response of each tumor to treatment will be determined based on RECIST 1.1 criteria. Clinical response will be defined as either stable disease or a decrease in the size of the tumor by radiographic imaging (which may include CT or MRI) using RECIST 1.1 criteria.
Time Frame
4 months post treatment
Title
Clinical Response Rate 8 months post treatment
Description
Participants will undergo radiographic evaluation 8 months after completion of all protocol therapy. The response of each tumor to treatment will be determined based on RECIST 1.1 criteria. Clinical response will be defined as either stable disease or a decrease in the size of the tumor by radiographic imaging (which may include CT or MRI) using RECIST 1.1 criteria
Time Frame
8 months post treatment
Title
Clinical Response Rate 12 months post treatment
Description
Participants will undergo radiographic evaluation 12 months after completion of all protocol therapy. The response of each tumor to treatment will be determined based on RECIST 1.1 criteria. Clinical response will be defined as either stable disease or a decrease in the size of the tumor by radiographic imaging (which may include CT or MRI) using RECIST 1.1 criteria.
Time Frame
12 months post treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed diagnosis of a solid tumor metastatic to bone, or a histologically confirmed diagnosis of osteosarcoma with either an unresectable primary tumor or metastases (including tumors with an intralesional resection).
Measurable disease on anatomic imaging that is also avid for phosphonate compounds as demonstrated by a positive 99mTc diphosphonate bone scan.
Adequate renal function, defined as a measured creatinine clearance >70 ml/min/1.73 m2 or normal radioisotope glomerular filtration rate (GFR).
Adequate hematologic function, defined as a platelet count > 50,000 cells/mm3 and an absolute neutrophil count (ANC) > 500 cells/mm3
Life expectancy of at least 8 weeks.
Karnofsky performance status > 50%
Subject must have adequately recovered from the effects of any prior chemotherapy, as determined by the treating physician and study team, based in part on organ function defined above. Toxicities from previous therapies must have recovered to Common Terminology Criteria for Adverse Events (CTCAE) 4.0 grade 2 or better.
Patients must have previously received effective treatment for their underlying disease and have no potentially curative options available.
Exclusion Criteria:
Subject has received prior radiotherapy to all known areas of current active disease or has a known contraindication to receiving radiotherapy.
Subject is pregnant or breastfeeding.
Patient is sexually active and does not agree to use accepted, effective forms of contraception.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Loeb, MD, PhD
Organizational Affiliation
Children's Hospital at Montefiore
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montefiore Medical Center-Children's Hospital
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Dose Finding Study of CycloSam® Combined With External Beam Radiotherapy
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