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.
Brief Title
A Dose Finding Study of CycloSam® Combined With 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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Osteosarcoma
Bone Metastases
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.
* 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
dosimetry
radiopharmaceutical
radiotherapy
Maximally tolerated dose
MTD
tumor
myelosuppression
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
65 Years
Minimum Age
15 Years
NCT Id
NCT03612466
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2018-8787
Overall Status
Withdrawn
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome 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.
Outcome Measure
Maximally Tolerated Dose
Outcome 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 Ids
Secondary Id
7R01CA163870-06
Secondary Outcomes
Outcome 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.
Outcome Time Frame
From date of enrollment until date of death from any cause, assessed up to 60 months
Outcome Measure
Overall Survival
Outcome 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.
Outcome Time Frame
Participants will be evaluated 4, 8, and 12 months after treatment.
Outcome Measure
Time To Progression
Outcome 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.
Outcome Time Frame
30 days post treatment
Outcome Measure
Clinical Response Rate 30 days post treatment
Outcome 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.
Outcome Time Frame
4 months post treatment
Outcome Measure
Clinical Response Rate 4 months post treatment
Outcome 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
Outcome Time Frame
8 months post treatment
Outcome Measure
Clinical Response Rate 8 months post treatment
Outcome 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.
Outcome Time Frame
12 months post treatment
Outcome Measure
Clinical Response Rate 12 months post treatment
Start Date
Start Date Type
Estimated
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
65
Minimum Age Number (converted to Years and rounded down)
15
Investigators
Investigator Type
Principal Investigator
Investigator Name
David Loeb
Investigator Email
david.loeb@einsteinmed.org
Investigator Phone
718-741-2342