OsteosarcomaPhase 1NCT03612466
A Dose Finding Study of CycloSam® Combined With External Beam Radiotherapy
A Phase 1 study testing 153Sm-DOTMP, External beam radiotherapy. and Calcium Carbonate in people with Osteosarcoma and Bone Metastases, run by Albert Einstein College of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 to 65 years
- Conditions the study is for
- Osteosarcoma, Bone Metastases
- What is being tested?
- 153Sm-DOTMP, External beam radiotherapy. and Calcium Carbonate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2022to Sep 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Medical Center-Children's Hospital
The Bronx, New York, 10461
About this study
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
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.
Read the 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.
- Conditions
- Osteosarcoma, Bone Metastases
- Being tested
- 153Sm-DOTMP, External beam radiotherapy., Calcium Carbonate, Mozobil, Neupogen Injectable Product
- Keywords
- dosimetry, radiopharmaceutical, radiotherapy, Maximally tolerated dose, MTD, tumor, myelosuppression
- Medical subject headings
- Osteosarcoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
153Sm-DOTMPDrug
Also called CycloSam
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.
External beam radiotherapy.Radiation
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)
Calcium CarbonateDrug
Calcium carbonate will be given to participants as prophylaxis against hypocalcemia..
MozobilDrug
Also called plerixafor
Participants who require stem cell collection will be given Mozobil to help mobilize hematopoietic stem cells into the circulation for collection.
Neupogen Injectable ProductDrug
Also called filgrastim
Participants who require stem cell collection will be given Neupogen to help mobilize hematopoietic stem cells into the circulation for collection.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Arm | Experimental | 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. Receives: Drug: 153Sm-DOTMP; Radiation: External beam radiotherapy.; Drug: Calcium Carbonate; Drug: Mozobil; Drug: Neupogen Injectable Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (6)
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.
Measured: From date of enrollment until date of death from any cause, assessed up to 60 months
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.
Measured: Participants will be evaluated 4, 8, and 12 months after treatment.
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.
Measured: 30 days post treatment
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.
Measured: 4 months post treatment
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
Measured: 8 months post treatment
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.
Measured: 12 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2018
- Study startAug 2022 (estimated)
- Primary completionJan 2023 (estimated)
- Study completionSep 2024 (estimated)
Why it stopped: Study withdrawn before any participants could be enrolled. Issues being able to effectively recruit participants into the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albert Einstein College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- David Loeb, MD, PhD, Principal investigator, Children's Hospital at Montefiore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03612466
- Sponsor's protocol ID
- 2018-8787
- Other IDs
- 7R01CA163870-06
- Status last verified
- Oct 2022
- First submitted
- 30 Jul 2018
- Last updated
- 14 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03612466
- Acronym / sponsor ID
- 2018-8787
- Conditions
- Osteosarcoma, Bone Metastases
- Keywords
- dosimetry, radiopharmaceutical, radiotherapy, Maximally tolerated dose, MTD, tumor, myelosuppression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study withdrawn before any participants could be enrolled. Issues being able to effectively recruit participants into the study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Albert Einstein College of MedicineUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2022 (estimated)
- Primary completion
- Jan 2023 (estimated)
- Study completion
- Sep 2024 (estimated)
- First posted
- 2 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Arm | Experimental | Drug: 153Sm-DOTMP, Radiation: External beam radiotherapy., Drug: Calcium Carbonate, Drug: Mozobil, Drug: Neupogen Injectable ProductDose 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. |
Who may qualify
- Ages
- 15 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 153Sm-DOTMPAlso: CycloSamFor 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. | Drug | Dose Escalation Arm |
| External beam radiotherapy.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) | Radiation | Dose Escalation Arm |
| Calcium CarbonateCalcium carbonate will be given to participants as prophylaxis against hypocalcemia.. | Drug | Dose Escalation Arm |
| MozobilAlso: plerixaforParticipants who require stem cell collection will be given Mozobil to help mobilize hematopoietic stem cells into the circulation for collection. | Drug | Dose Escalation Arm |
| Neupogen Injectable ProductAlso: filgrastimParticipants who require stem cell collection will be given Neupogen to help mobilize hematopoietic stem cells into the circulation for collection. | Drug | Dose Escalation Arm |
Primary outcome
Maximally Tolerated Dose
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
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.
6 secondary outcomes
Overall Survival
Time frame: From date of enrollment until date of death from any cause, assessed up to 60 months
Time To Progression
Time frame: Participants will be evaluated 4, 8, and 12 months after treatment.
Clinical Response Rate 30 days post treatment
Time frame: 30 days post treatment
Clinical Response Rate 4 months post treatment
Time frame: 4 months post treatment
Clinical Response Rate 8 months post treatment
Time frame: 8 months post treatment
Clinical Response Rate 12 months post treatment
Time frame: 12 months post treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Loeb, MD, PhD principal investigator
Children's Hospital at Montefiore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 153Sm-DOTMP, External beam radiotherapy. and Calcium Carbonate in people with Osteosarcoma and Bone Metastases, run by Albert Einstein College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximally Tolerated Dose (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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2022; AzTrials last refreshed its copy on 2 Nov 2026.