IGIMRT Dosing Schedules for Cancer Spread to Bone/Spine

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Memorial Sloan Kettering Cancer Center

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

220 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out which way of giving high-dose radiation works best for treatment of cancer that has spread to bone, the spine, soft tissue, or lymph nodes. This study will look at the effects, good and/or bad, of giving 27 Gy in three fractions (3 days) or 24 Gy in one fraction (1 day) using image-guided intensity-modulated radiotherapy (IG-IMRT). IG-IMRT is radiation that is given directly to the cancer site and reduces the exposure to normal tissue. Currently there are no studies that compare the effects of giving radiation in either hypofractionated doses (higher total doses of radiation spread out over several treatment days) or a single-fraction dose (entire radiation dose given in one treatment session). The patient may be asked to participate in an additional part of this study where we will get a a (DW/DCE) MRI before treatment start and within one hour after radiation treatment. If the patient is asked to take part in this portion of the study, all they will need to do is get up to 3 MRIs with standard contrast injection. The purpose of this is to see if as a result of the treatment there are changes in the blood flow going to the cancer which could suggest that the treatment may be successful. In addition some patients can present new lesions and may be asked if they would like to have these new lesions treated on the protocol. If they are given this option, this will not extend their follow up period. The follow up of the new lesions will match with the prior follow up dates.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, chemotherapy cannot be given on the day of the planned radiotherapy treatment.

What data supports the effectiveness of the treatment IGIMRT for cancer spread to bone/spine?

Research shows that increasing the dose of image-guided intensity-modulated radiotherapy (IG-IMRT) can lead to better pain relief for spinal metastases, which suggests that higher doses might be more effective for treating cancer that has spread to the spine. ^{1 2 3 4 5}

Is IGIMRT generally safe for humans?

IGIMRT has been used in prostate cancer patients, where it showed some gastrointestinal (GI) and genitourinary (GU) side effects, but these were managed by adjusting the dose. This suggests that while there can be side effects, they are known and can be addressed. ^{1 2 3 6 7}

How is the IGIMRT treatment for cancer spread to bone/spine different from other treatments?

The IGIMRT treatment for cancer spread to bone/spine is unique because it uses high-dose radiation delivered in fewer sessions (either 27 Gy in 3 fractions or a single dose of 24 Gy), which may provide effective pain relief and tumor control while minimizing damage to surrounding healthy tissues. This approach contrasts with traditional regimens that often involve more sessions with lower doses. ^{1 2 8 9 10}

Research Team

Yoshiya Yamada, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with Stage IV cancer that has spread to bone, spine, soft tissue, or lymph nodes. They must have a confirmed diagnosis of cancer like carcinoma, sarcoma, or melanoma and measurable disease. Participants need good physical functioning (KPS ≥ 80) and normal bone marrow function. Pregnant women or those breastfeeding are excluded.

Inclusion Criteria

Measurable disease defined as: ≥ 10mm for soft-tissue lesions, ≥ 15mm on the short axis of lymph nodes

My cancer has spread to my bones, spine, soft tissues, or lymph nodes.

My cancer is at stage IV and has spread to distant parts of my body.

Exclusion Criteria

I have had radiation therapy on the cancer area before.

My disease is close to my spinal cord, less than 2 mm away.

I will receive chemotherapy on the same day as my radiotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive either 27 Gy in three fractions over 3 days or 24 Gy in one fraction over 1 day using image-guided intensity-modulated radiotherapy (IG-IMRT)

1-3 days

1-3 visits (in-person)

MRI Assessment

Participants may undergo up to 3 MRIs with standard contrast injection to assess changes in blood flow to the cancer

1 day

Up to 3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in tumor perfusion and SUV uptake

2 years

Treatment Details

Interventions

• IGIMRT 27 Gy in 3 fractions
• IGIMRT using a single dose of 24 Gy

Trial Overview The study compares two ways of delivering high-dose radiation using IG-IMRT: one group receives a single dose of 24 Gy in one day; the other gets 27 Gy across three days. The goal is to see which method is more effective for treating metastatic cancer at specific sites.

Participant Groups

Group I: stereotactic IGIMRT using a single dose of 24 Gy Experimental Treatment 1 Intervention

This is a phase III, multicenter, randomized, study comparing two dosing schedules for hypofractionated image-guided radiation therapy to bone, spine, soft tissue, and lymph nodes in patients with metastatic disease

Group II: stereotactic IGIMRT 27 Gy in 3 fractions Experimental Treatment 1 Intervention

This is a phase III, multicenter, randomized, study comparing two dosing schedules for hypofractionated image-guided radiation therapy to bone, spine, soft tissue, and lymph nodes in patients with metastatic disease

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

University of Pisa

Collaborator

Trials

153

Recruited

84,700+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

The Champalimaud Centre, Lisbon, Portugal

Collaborator

Trials

2

Recruited

330+

Findings from Research

In a study comparing two radiotherapy regimens for spinal metastases, the dose-escalation group receiving 60-66 Gy showed significantly better pain relief outcomes after one and three months compared to the 30-Gy group, with complete pain relief rates of 73.69% and 41.38%, respectively.

The dose-escalation regimen not only improved pain relief but also demonstrated a trend towards longer overall survival and lower acute radiation toxicities, while no late radiation toxicities were observed in either group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation by image-guided intensity-modulated radiotherapy leads to an increase in pain relief for spinal metastases: a comparison study with a regimen of 30 Gy in 10 fractions. He, J., Xiao, J., Peng, X., et al.[2022]

Patients treated with image-guided intensity modulated radiation therapy (IG-IMRT) received significantly lower radiation doses to critical organs like the anorectum, anal canal, and bladder compared to those treated with 3D conformal radiation therapy (3D-CRT), which can lead to better safety outcomes.

IG-IMRT resulted in lower rates of acute gastrointestinal and genitourinary toxicity, with grade ≥2 GI toxicity at 29% compared to 49% for 3D-CRT, and GU toxicity at 38% compared to 48%, indicating that IG-IMRT may provide a safer treatment option for prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity after image-guided intensity modulated radiation therapy compared to 3D conformal radiation therapy in prostate cancer patients. Wortel, RC., Incrocci, L., Pos, FJ., et al.[2022]

In a Phase I clinical trial involving 19 patients with glioblastoma, the maximum tolerated dose of fractionated intensity-modulated radiotherapy (IMRT) combined with temozolomide (TMZ) was determined to be 65 Gy, delivered in 25 fractions over 5 weeks, without any dose-limiting toxicities observed.

The treatment was well tolerated, with only mild to moderate (Grade 1-2) neurologic and skin toxicities reported, and no severe late neurologic toxicities, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose-escalation study (ISIDE-BT-1) of accelerated IMRT with temozolomide in patients with glioblastoma. Morganti, AG., Balducci, M., Salvati, M., et al.[2018]

In a trial involving 40 glioblastoma patients, the maximum tolerated dose (MTD) of intensity-modulated radiotherapy (IMRT) was determined to be 70 Gy, delivered in 25 fractions, without unacceptable acute toxicity.

The study demonstrated that this high dose of radiation, combined with standard doses of temozolomide (TMZ), did not result in significant late neurological toxicity after a median follow-up of 25 months, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1). Massaccesi, M., Ferro, M., Cilla, S., et al.[2022]

In a phase I clinical trial involving nine patients with glioblastoma, simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) combined with temozolomide was found to be feasible and well tolerated up to a maximum dose of 80Gy.

No dose-limiting toxicities were observed at the highest dose level, indicating that this treatment combination may be safe for patients with malignant glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma. Truc, G., Bernier, V., Mirjolet, C., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Dose escalation by image-guided intensity-modulated radiotherapy leads to an increase in pain relief for spinal metastases: a comparison study with a regimen of 30 Gy in 10 fractions. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Risk of fracture after single fraction image-guided intensity-modulated radiation therapy to spinal metastases. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Does image-guided radiotherapy improve toxicity profile in whole pelvic-treated high-risk prostate cancer? Comparison between IG-IMRT and IMRT. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Impact of dose on local failure rates after image-guided reirradiation of recurrent paraspinal metastases. [2011]

5. United States pubmed.ncbi.nlm.nih.gov

Selection of prescription isodose line for brain metastases treated with volumetric modulated arc radiotherapy. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Acute toxicity after image-guided intensity modulated radiation therapy compared to 3D conformal radiation therapy in prostate cancer patients. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

Long-term Outcomes of a Dose-reduction Trial to Decrease Late Gastrointestinal Toxicity in Patients with Prostate Cancer Receiving Soft Tissue-matched Image-guided Intensity-modulated Radiotherapy. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

A phase I dose-escalation study (ISIDE-BT-1) of accelerated IMRT with temozolomide in patients with glioblastoma. [2018]

9. Japan pubmed.ncbi.nlm.nih.gov

Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1). [2022]

10. France pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma. [2018]