A Dose Finding Study of CycloSam® Combined With External Beam Radiotherapy

NCT03612466 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 2018-87877R01CA163870-06
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteosarcoma; Bone Metastases

Keywords

dosimetry; radiopharmaceutical; radiotherapy; Maximally tolerated dose; MTD; tumor; myelosuppression

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  From date of enrollment until date of death from any cause, assessed up to 60 months

• Time To Progression

  Participants will be evaluated 4, 8, and 12 months after treatment.

• Clinical Response Rate 30 days post treatment

  30 days post treatment

• Clinical Response Rate 4 months post treatment

  4 months post treatment

• Clinical Response Rate 8 months post treatment

  8 months post treatment

Study Arms (1)

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.

Drug: 153Sm-DOTMP; Radiation: External beam radiotherapy.; Drug: Calcium Carbonate; Drug: Mozobil; Drug: Neupogen Injectable Product

Interventions

153Sm-DOTMP DRUG

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.

Also known as: CycloSam

Dose Escalation Arm

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)

Dose Escalation Arm

Calcium Carbonate DRUG

Calcium carbonate will be given to participants as prophylaxis against hypocalcemia..

Dose Escalation Arm

Mozobil DRUG

Participants who require stem cell collection will be given Mozobil to help mobilize hematopoietic stem cells into the circulation for collection.

Also known as: plerixafor

Dose Escalation Arm

Neupogen Injectable Product DRUG

Participants who require stem cell collection will be given Neupogen to help mobilize hematopoietic stem cells into the circulation for collection.

Also known as: filgrastim

Dose Escalation Arm

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Montefiore Medical Center-Children's Hospital

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Osteosarcoma; Neoplasms

Interventions

Calcium Carbonate; plerixafor; Filgrastim

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma

Intervention Hierarchy (Ancestors)

Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• David Loeb, MD, PhD

  Children's Hospital at Montefiore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 2, 2018
• Study Start: August 1, 2022
• Primary Completion: January 1, 2023
• Study Completion: September 1, 2024
• Last Updated: October 14, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)