Trial Outcomes & Findings for A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) in High Risk Abdominal Neuroblastoma (NCT NCT01440283)

NCT ID: NCT01440283

Last Updated: 2016-03-03

Results Overview

Measured from start of radiation therapy to date of local-regional failure or last follow-up.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 14 participants
• Primary outcome timeframe: 2 years after last patient enrollment
• Results posted on: 2016-03-03

Participant Flow

Fourteen participants were enrolled on the study between September 2011 and July 2013.

Participant milestones

Measure	Treatment Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma treatment regimen were eligible to enroll prior to surgical resection of the primary tumor. Following implantation of fiducial markers within the tumor bed and autologous hematopoietic rescue, patients began the planning process for abdominal irradiation. Intensity Modulated Radiation Therapy (IMRT) delivery followed current conventional volume-targeting guidelines, however, appropriate application within the abdomen was determined by ascertaining intra-abdominal organ motion and the potential for reducing normal tissue dose, while simultaneously increasing dose delivered to target tissues, particularly when dose escalation for gross residual disease was required.
Overall Study STARTED	14
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Measure	Treatment Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma treatment regimen were eligible to enroll prior to surgical resection of the primary tumor. Following implantation of fiducial markers within the tumor bed and autologous hematopoietic rescue, patients began the planning process for abdominal irradiation. Intensity Modulated Radiation Therapy (IMRT) delivery followed current conventional volume-targeting guidelines, however, appropriate application within the abdomen was determined by ascertaining intra-abdominal organ motion and the potential for reducing normal tissue dose, while simultaneously increasing dose delivered to target tissues, particularly when dose escalation for gross residual disease was required.
Overall Study Death	3
Overall Study Withdrawal by Subject	4
Overall Study Physician Decision	3

Baseline Characteristics

A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) in High Risk Abdominal Neuroblastoma

Baseline characteristics by cohort

Measure	Treatment n=14 Participants Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma treatment regimen were eligible to enroll prior to surgical resection of the primary tumor. Following implantation of fiducial markers within the tumor bed and autologous hematopoietic rescue, patients began the planning process for abdominal irradiation. Intensity Modulated Radiation Therapy (IMRT) delivery followed current conventional volume-targeting guidelines, however, appropriate application within the abdomen was determined by ascertaining intra-abdominal organ motion and the potential for reducing normal tissue dose, while simultaneously increasing dose delivered to target tissues, particularly when dose escalation for gross residual disease was required.
Age, Continuous	4.1 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years after last patient enrollment

Measured from start of radiation therapy to date of local-regional failure or last follow-up.

Outcome measures

Measure	Treatment n=14 Participants Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma treatment regimen were eligible to enroll prior to surgical resection of the primary tumor. Following implantation of fiducial markers within the tumor bed and autologous hematopoietic rescue, patients began the planning process for abdominal irradiation. Intensity Modulated Radiation Therapy (IMRT) delivery followed current conventional volume-targeting guidelines, however, appropriate application within the abdomen was determined by ascertaining intra-abdominal organ motion and the potential for reducing normal tissue dose, while simultaneously increasing dose delivered to target tissues, particularly when dose escalation for gross residual disease was required.	Right Kidney: A-P Nine participants who underwent all 3 scans.	Right Kidney: S-I Nine participants who underwent all 3 scans.	Left Kidney: M-L Nine participants who underwent all 3 scans.	Left Kidney: A-P Nine participants who underwent all 3 scans.	Left Kidney: S-I Nine participants who underwent all 3 scans.
Percentage of Participants Who Failed to Reach Local-regional Control	0 percentage of participants	—	—	—	—	—

PRIMARY outcome

Timeframe: 2 years after last patient enrollment

Population: There was no local-regional failure noted (please see outcome #1), therefore, no pattern of failure could be determined.

Categorical measurements of local-regional failure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and approximately 2 weeks following initiation of irradiation.

Population: Five participants did not receive all scans for motion evaluations and are excluded from the analysis. Age at scan ranges from 8 months to 9.5 years old. The median age was 3.8 years.

Normal tissue motion-defining measurements were obtained which can guide future more conformal therapeutic regimens incorporating smaller volumes of uninvolved tissue. Participants underwent CT simulation and 4D-CT acquisition as well as real-time dynamic 4D MRI prior to the start of radiation therapy (RT), and a subsequent repeat 4D-CT was obtained approximately 2 weeks after the start of RT. The imaging position was supine with general anesthesia. Renal edges were marked in a customized graphical interface for each imaging series with the image resolution determining the minimum motion extent. Vectors of renal edge motion were quantified in the anterior-posterior (A-P), medial-lateral (M-L), and superior-inferior (S-I) dimensions. The motion extent derived from the MRI dataset was considered in defining the margins for RT treatment planning.

Outcome measures

Measure	Treatment n=9 Participants Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma treatment regimen were eligible to enroll prior to surgical resection of the primary tumor. Following implantation of fiducial markers within the tumor bed and autologous hematopoietic rescue, patients began the planning process for abdominal irradiation. Intensity Modulated Radiation Therapy (IMRT) delivery followed current conventional volume-targeting guidelines, however, appropriate application within the abdomen was determined by ascertaining intra-abdominal organ motion and the potential for reducing normal tissue dose, while simultaneously increasing dose delivered to target tissues, particularly when dose escalation for gross residual disease was required.	Right Kidney: A-P n=9 Participants Nine participants who underwent all 3 scans.	Right Kidney: S-I n=9 Participants Nine participants who underwent all 3 scans.	Left Kidney: M-L n=9 Participants Nine participants who underwent all 3 scans.	Left Kidney: A-P n=9 Participants Nine participants who underwent all 3 scans.	Left Kidney: S-I n=9 Participants Nine participants who underwent all 3 scans.
Quantify the Range of Organ Movement During the Breathing Phase Measured by 4-dimensional MRI (4DMRI) and 4DCT. Baseline 4D CT	0.3 mm Standard Deviation 0.4	0.5 mm Standard Deviation 0.5	2.6 mm Standard Deviation 1.5	0.5 mm Standard Deviation 0.5	0.4 mm Standard Deviation 0.4	2.2 mm Standard Deviation 1.8
Quantify the Range of Organ Movement During the Breathing Phase Measured by 4-dimensional MRI (4DMRI) and 4DCT. Week 2 4D CT	0.4 mm Standard Deviation 0.3	0.4 mm Standard Deviation 0.4	2.8 mm Standard Deviation 0.8	0.5 mm Standard Deviation 0.3	0.5 mm Standard Deviation 0.2	2.3 mm Standard Deviation 1.3
Quantify the Range of Organ Movement During the Breathing Phase Measured by 4-dimensional MRI (4DMRI) and 4DCT. Baseline MRI	0.8 mm Standard Deviation 1.0	0.5 mm Standard Deviation 0.7	2.6 mm Standard Deviation 0.8	0.5 mm Standard Deviation 0.7	0.3 mm Standard Deviation 0.6	2.3 mm Standard Deviation 0.8

SECONDARY outcome

Timeframe: Baseline and approximately 2 weeks following initiation of irradiation.

Population: All participants underwent complete surgery prior to RT, therefore, no visible tumor tissue target was available for movement measurements.

Obtain target tissue motion-defining data which can guide future more conformal therapeutic regimens incorporating smaller volumes of uninvolved tissue.

Outcome measures

Outcome data not reported

Adverse Events

Treatment

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment n=14 participants at risk Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma treatment regimen were eligible to enroll prior to surgical resection of the primary tumor. Following implantation of fiducial markers within the tumor bed and autologous hematopoietic rescue, patients began the planning process for abdominal irradiation. Intensity Modulated Radiation Therapy (IMRT) delivery followed current conventional volume-targeting guidelines, however, appropriate application within the abdomen was determined by ascertaining intra-abdominal organ motion and the potential for reducing normal tissue dose, while simultaneously increasing dose delivered to target tissues, particularly when dose escalation for gross residual disease was required.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	7.1% 1/14 • Number of events 1 • Adverse events were collected from the initiation of radiation therapy until completion of study, removal from study, or disease recurrence, up to 2 years after the last participant enrollment. The therapy delivered on protocol was standard of care (standard indications for radiation and standard radiation doses) and was not expected to generate unexpected toxicities related to abdominal radiation.
Injury, poisoning and procedural complications Intraoperative hemorrhage	7.1% 1/14 • Number of events 1 • Adverse events were collected from the initiation of radiation therapy until completion of study, removal from study, or disease recurrence, up to 2 years after the last participant enrollment. The therapy delivered on protocol was standard of care (standard indications for radiation and standard radiation doses) and was not expected to generate unexpected toxicities related to abdominal radiation.

Other adverse events

Measure	Treatment n=14 participants at risk Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma treatment regimen were eligible to enroll prior to surgical resection of the primary tumor. Following implantation of fiducial markers within the tumor bed and autologous hematopoietic rescue, patients began the planning process for abdominal irradiation. Intensity Modulated Radiation Therapy (IMRT) delivery followed current conventional volume-targeting guidelines, however, appropriate application within the abdomen was determined by ascertaining intra-abdominal organ motion and the potential for reducing normal tissue dose, while simultaneously increasing dose delivered to target tissues, particularly when dose escalation for gross residual disease was required.
Blood and lymphatic system disorders Lymphocyte count decreased	57.1% 8/14 • Number of events 21 • Adverse events were collected from the initiation of radiation therapy until completion of study, removal from study, or disease recurrence, up to 2 years after the last participant enrollment. The therapy delivered on protocol was standard of care (standard indications for radiation and standard radiation doses) and was not expected to generate unexpected toxicities related to abdominal radiation.
Blood and lymphatic system disorders Neutrophil count decreased	7.1% 1/14 • Number of events 2 • Adverse events were collected from the initiation of radiation therapy until completion of study, removal from study, or disease recurrence, up to 2 years after the last participant enrollment. The therapy delivered on protocol was standard of care (standard indications for radiation and standard radiation doses) and was not expected to generate unexpected toxicities related to abdominal radiation.
Blood and lymphatic system disorders Platelet count decreased	35.7% 5/14 • Number of events 11 • Adverse events were collected from the initiation of radiation therapy until completion of study, removal from study, or disease recurrence, up to 2 years after the last participant enrollment. The therapy delivered on protocol was standard of care (standard indications for radiation and standard radiation doses) and was not expected to generate unexpected toxicities related to abdominal radiation.
Blood and lymphatic system disorders White blood cell decreased	14.3% 2/14 • Number of events 2 • Adverse events were collected from the initiation of radiation therapy until completion of study, removal from study, or disease recurrence, up to 2 years after the last participant enrollment. The therapy delivered on protocol was standard of care (standard indications for radiation and standard radiation doses) and was not expected to generate unexpected toxicities related to abdominal radiation.

Additional Information

Chia-ho Hua, PhD

St. Jude Children's Research Hospital

Phone: 901-595-3610

Email: chia-ho.hua@stjude.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place