Evaluation of a Novel Absorbable Radiopaque Hydrogel in Patients Undergoing Image-guided Radiotherapy for Pancreatic Adenocarcinoma

Radiopaque Hydrogel in Patients Undergoing Radiotherapy for Pancreatic Cancer



Sponsors


Source

Sidney Kimmel Comprehensive Cancer Center

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

No

Is Fda Regulated Device

No

Is Us Export

No


Brief Summary

The goal of this pilot imaging study is to evaluate the visibility of marking the interface
between the pancreas and duodenum with TraceIT Tissue Marker. Patients with a pathologically
confirmed diagnosis of BR/LAPC (borderline resectable/locally advanced pancreatic cancer)
pancreatic adenocarcinomas indicated for neo-adjuvant image-guided radiotherapy with SBRT
(stereotactic body radiation therapy) will be enrolled. This study will thus set the stage
for further investigations using the TraceIT Tissue Marker to avoid duodenum toxicity with
imaging localization, enabling further dose intensification with SBRT or IMRT to improve the
clinical outcomes in BR/LAPC.

Detailed Description

Pancreatic ductal adenocarcinoma is now the third leading cause of cancer-related death, with
a devastating 5-year overall survival (OS) rate of nearly 8%, despite having the 12th most
common incidence of all malignancies in the United States. One-third of patients will present
with borderline resectable or unresectable, locally advanced pancreatic cancer (BR/LAPC). In
the cases of LAPC, chemotherapy with or without radiation may be recommended to improve the
quality of life by relieving symptoms and extending survival. Despite aggressive combined
modality therapy, the median survival remains between 9 and 15 months.

Current guidelines for the management of BR/LAPC patients include single- or multi-agent
chemotherapy or chemoradiation (CRT) in sequence with chemotherapy. Results of studies
comparing chemotherapy alone to CRT for patients with BR/LAPC are mixed. The importance of
local control or delaying local progression on improving morbidity and possibly mortality in
patients with pancreatic cancer is supported by autopsy data demonstrating that 30% of
patients die of locally destructive disease. It follows that in the cases of LAPC, advanced
radiation therapy techniques using dose-escalation with intensity modulated radiotherapy
(IMRT) and stereotactic body radiotherapy (SBRT) are potential strategies to improve local
control.

A consistent challenge to dose-escalation with IMRT (intensity modulation radiation therapy)
or SBRT is the sensitivity of the surrounding gastrointestinal organs, particularly the small
bowel which is directly adjacent to the head of the pancreas head of the pancreas (HOP). For
BR/LAPC patients treated with CRT, advances in image guidance have provided the opportunity
to safely deliver higher biologically effective doses of radiation therapy using IMRT of >70
Gy (57.25 Gy in 25 fractions, BED 70.36 Gy) compared to standard fractionation regimens
(50.40 Gy in 28 fractions or 50 Gy in 25 fractions, BED 59.47 Gy and 60 Gy, respectively).
Those patients who underwent dose-escalated CRT with BED>70 Gy, did have a superior OS
compared to those receiving BED<70 Gy, supporting the utility of dose-escalation in improving
long-term outcomes. SBRT involves a short course of radiation therapy, five fractions or
less, and has demonstrated higher rates of local control compared to CRT in other disease
sites. Early studies evaluating SBRT for pancreatic cancer utilized single fractions of 25
Gy, resulting in local control rates of 100% at 1 year but unacceptably high rates of
gastrointestinal toxicity. More recently, hypofractionated SBRT (33 Gy total, 6.6 Gy daily
fractions) has been evaluated and utilized by our group in an effort to reduce the toxicity
of therapy, with results demonstrating nearly 80% rate of freedom from local progression at
one year and an acceptable 11% long-term gastrointestinal toxicity. Outcomes with SBRT are
thus promising; however, higher local control rates with dose-escalation may be achievable,
but current practice is limited due to risks of toxicity.

The goal of this pilot imaging study is to evaluate the visibility of marking the interface
between the pancreas and duodenum with TraceIT Tissue Marker. Patients with a pathologically
confirmed diagnosis of BR/LAPC pancreatic adenocarcinomas indicated for neo-adjuvant
image-guided radiotherapy with SBRT will be enrolled. This study will thus set the stage for
further investigations using the TraceIT Tissue Marker to avoid duodenum toxicity with
imaging localization, enabling further dose intensification with SBRT or IMRT to improve the
clinical outcomes in BR/LAPC.

Overall Status

Not yet recruiting

Start Date

2017-12-01

Completion Date

2021-12-01

Primary Completion Date

2020-12-01

Phase

N/A

Study Type

Interventional

Primary Outcome

Measure

Time Frame

TraceIT Tissue Marker
day 1

Enrollment

21

Condition


Intervention

Intervention Type

Device

Intervention Name


Description

The TraceIT injection will be performed during the endoscopic fiducial placement which is the standard of care. CTs to serially confirm TraceIT positioning will be performed on the same day during patient visits for their middle (2nd or 3rd fraction) and last (5th fraction) radiation therapy treatments.

Arm Group Label

TraceIT tissue marker injection


Eligibility

Criteria

Inclusion Criteria:

1. Age ≥18 years old

2. BR/LAPC pancreatic carcinoma disease

3. Radiotherapy or chemoradiotherapy for treatment of the disease is indicated with the
intent for eventual surgical resection

4. Subjects Screening/Baseline laboratory testing must meet the following laboratory
value criteria:

1. White blood cell count: ≥ 3.0 x 109/L

2. Absolute neutrophil count (ANC): ≥ 1.5 x 109/L

3. Platelets: ≥ 100 x 109/L

4. Total bilirubin: ≤ 2.0 times upper limit of normal (ULN)

5. AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase): ≤ 3.0 times
institutional upper normal limit

6. Serum creatinine: 1.5 times ULN (upper limit of normal)

7. INR (international normalized ratio): < 1.5

8. Serum pregnancy: Negative

9. Hemoglobin: ≥ 8.0 g/dl

5. Zubrod Performance Status 0-2

6. Subject or authorized representative, has been informed of the nature of the study and
has provided written informed consent, approved by the appropriate Institutional
Review Board (IRB) of the respective clinical site.

Exclusion Criteria:

1. Previous thoracic radiotherapy

2. Any GI (gastrointestinal) abnormality that would interfere with the ability to access
the injection site

3. Active gastroduodenal ulcer or watery diarrhea

4. Active bleeding disorder or a clinically significant coagulopathy defined as a PTT
(Partial thromboplastin time) >35s or INR>1.4 or platelet count less than 100,000 per
mm3.

5. Active inflammatory or infectious process involving the gastrointestinal tract based
on positive diagnosis or suspected diagnosis in the presence of fever>38°C or
WBC>12,000/uL.

6. Compromised immune system: WBC (white blood count) <4000/uL or >12,000/uL.

7. History of Chronic Renal Failure.

8. Documented history of uncontrolled diabetes (i.e., symptomatic hyperglycemia that
cannot be medically managed, fasting blood glucose level above 300 mg/dL, and/or
frequent swings between hyperglycemia and hypoglycemia)

9. Currently enrolled in another investigational drug or device trial that clinically
interferes with this study.

10. Unable to comply with the study requirements or follow-up schedule.

11. Any condition or comorbidity that the Investigator believes would interfere with the
intent of the study or would make participation not in the best interest of the
subject.

12. Pregnancy, breast-feeding, women of child-bearing age must use contraceptives

Gender

All

Minimum Age

18 Years

Maximum Age

100 Years

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Amol Narang, MD
Principal Investigator
Johns Hopkins SKCCC

Overall Contact

Last Name

Kai Ding, MD

Phone

319-321-0032

Email



Verification Date

2017-10-01

Lastchanged Date

2017-10-16

Firstreceived Date

2017-10-05

Responsible Party

Responsible Party Type

Sponsor


Has Expanded Access

No

Condition Browse


Secondary Id

IRB00151816

Number Of Arms

1

Arm Group

Arm Group Label

TraceIT tissue marker injection

Arm Group Type

Experimental

Description

The TraceIT injection will be performed during the endoscopic fiducial placement which is the standard of care. CTs to serially confirm TraceIT positioning will be performed on the same day during patient visits for their middle (2nd or 3rd fraction) and last (5th fraction) radiation therapy treatments


Firstreceived Results Date

N/A

Firstreceived Results Disposition Date

N/A

Study Design Info

Intervention Model

Single Group Assignment

Intervention Model Description

marking the interface between the pancreas and duodenum with TraceIT Tissue Marker in patients undergoing image-guided radiotherapy

Primary Purpose

Treatment

Masking

None (Open Label)


Study First Submitted

October 5, 2017

Study First Submitted Qc

October 5, 2017

Study First Posted

October 11, 2017

Last Update Submitted

October 16, 2017

Last Update Submitted Qc

October 16, 2017

Last Update Posted

October 18, 2017


ClinicalTrials.gov processed this data on October 18, 2017

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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