A Pilot Study to Determine the Feasibility of Stereotactic Body Radiation Therapy Following Chemotherapy for Unresectable Perihilar Cholangiocarcinoma. "The STRONG Trial"

Stereotactic Body Radiation Therapy for Unresectable Perihilar Cholangiocarcinoma



Sponsors


Source

Erasmus Medical Center

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


Brief Summary

Rationale:

For patients with perihilar cholangiocarcinoma, surgery is the only treatment modality that
can result in cure. Unfortunately, in the majority of these patients the tumors are found to
be unresectable at presentation due to local invasive tumor growth or the presence of distal
metastases. For patients with unresectable cholangiocarcinoma palliative chemotherapy is the
standard treatment yielding an estimated median overall survival of 12-15.2 months. There is
no evidence from randomized trials that support the routine use of stereotactic body
radiation therapy (SBRT) for cholangiocarcinoma. However, small and most often retrospective
studies combining chemotherapy with SBRT showed promising results with overall survival
reaching up to 33-35 months.

Based upon these observations, the investigators designed a local feasibility trial with SBRT
after chemotherapy in patients with unresectable perihilar cholangiocarcinoma in order to try
to confirm the observed tolerability of adding SBRT to standard chemotherapy. The expected
time to include the required patients for this pilot study will be one year.

Objective:

To assess feasibility of SBRT as add on treatment after standard chemotherapy.

Study design:

Local feasibility trial.

Study population:

Patients diagnosed with perihilar cholangiocarcinoma, 18 years of age or older, T1-4 N0-1 M0
(AJCC 7th Edition), after completion of standard chemotherapy. Exclusion criteria are local
tumor growth into either stomach, colon, duodenum, pancreas or abdominal wall. Sample size
will be 6 patients.

Intervention:

SBRT will be delivered in 15 fractions of 3 to 4.5Gy after 8 cycles of chemotherapy. In case
of toxicity causing premature termination of systemic treatment, the patient can still
proceed to SBRT.

Main study parameters/endpoints:

The primary endpoint of this study is feasibility measured by radiotherapy induced toxicity
according to CTC v4.0.3.

Secondary endpoints will be:

- Quality of life

- Local progression

- Progression free survival

- Overall survival

- Cellular radiosensitivity.

Detailed Description

For patients with perihilar cholangiocarcinoma, surgery is the only treatment modality that
can result in cure. Unfortunately, in the majority of these patients the tumors are found to
be unresectable at presentation due to local invasive tumor growth or the presence of distant
metastases. For these patients palliative chemotherapy is the standard treatment yielding an
estimated median overall survival of 12-15.2 months. There is no evidence from randomized
trials that supports the routine use of stereotactic body radiation therapy (SBRT) for
unresectable cholangiocarcinoma. However, small and most often retrospective studies
combining chemotherapy with SBRT showed promising results with overall survival reaching up
to 33-35 months.

This pilot study is designed as a first step to confirm and extend these findings. Up to six
patients diagnosed with unresectable perihilar cholangiocarcinoma will be treated with
standard chemotherapy followed by SBRT in order to assess possible severe side effects of the
treatment. As part of this research, patients will be followed with CT- or MRI-scan and blood
tests exams until progression. In addition to this clinical evaluation, the investigators
will also work towards developing a predictive assay for radiotherapy response of both normal
and tumor tissue by establishing normal tissue and tumor organoids and determining several
key parameters for their response to ionizing radiation treatment.

Overall Status

Recruiting

Start Date

2017-09-01

Completion Date

2020-12-01

Primary Completion Date

2018-09-01

Phase

N/A

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Acute toxicity
3 months

Secondary Outcome

Measure

Time Frame

Quality of life
2 years
Quality of life
2 years
Quality of life
2 years
Local progression
2 years
Local progression
2 years
Progression free survival
2 years
Overall survival
2 years
Cellular radiosensitivity
2 years

Enrollment

6

Condition


Intervention

Intervention Type

Radiation

Intervention Name


Description

15 fractions of 3-4,5 Gy (risk-adapted)

Arm Group Label

Stereotactic body radiation therapy


Eligibility

Criteria

Inclusion criteria:

In order to be eligible to participate in this study, a subject must be discussed in a
multidisciplinary liver tumor board and should meet all of the following criteria:

- Patients diagnosed with perihilar cholangiocarcinoma according to the criteria of the
Mayo Clinic, Rochester:

- Positive or strongly suspicious intraluminal brush or biopsy or,

- A radiographic malignant appearing stricture plus either:

- CA 19-9>100 U/ml in the absence of acute bacterial cholangitis, or

- polysomy on FISH, or

- a well-defined mass on cross sectional imaging.

- One tumor mass

- Unresectable tumor

- Finished chemotherapy treatment with Gemcitabine and Cisplatin, preferably 8 cycles.
If less cycles are given, patients are still eligible for this study.

- T1-T4 (AJCC staging 7th edition), before chemotherapy

- N0-N1 (AJCC staging 7th edition), radiologically or pathologically suspect, before
chemotherapy

- Measurable disease to be selected as a target on CT/MRI-scan, according to RECIST
criteria, after chemotherapy within 6 weeks prior to inclusion

- Tumor visibility on CT

- If liver cirrhosis is present, it should be well compensated, with Child-Pugh grade A.

- Age ≥ 18 years

- ECOG performance status 0-1

- Bilirubin ≤1.5 times normal value, AST/ALT ≤5 times ULN, within 6 weeks prior to
inclusion

- Platelets ≥ 50x10E9/ l, Leukocytes > 1.5x10E9/l, Hb > 6 mmol/l, within 6 weeks prior
to inclusion

- Written informed consent, after chemotherapy

- Willing and able to comply to the follow-up schedule

- Able to start SBRT within 12 weeks after completion of chemotherapy.

Exclusion criteria:

- Eligibility for resection

- Prior surgery or transplantation

- Multifocal tumor

- Tumor extension in stomach, colon, duodenum, pancreas or abdominal wall.

- N2, (AJCC staging 7th edition), radiologically or pathologically suspect, before
chemotherapy

- Distant metastases

- Progression (local or distant) during or after chemotherapy Ascites

- Previous radiotherapy to the liver

- Current pregnancy

Gender

All

Minimum Age

18 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Alejandra Méndez Romero, MD, PhD
Principal Investigator
Erasmus Medical Center

Overall Contact

Last Name

Alejandra Méndez Romero, MD, PhD

Phone

+31 (0)10 7035829

Email



Location

Facility

Status

Contact

Investigator

Erasmus MC
Rotterdam Zuid Holland 3015 CE Netherlands
Recruiting
Last Name: Alejandra Mendez Romero, MD PhD
Phone: +31 (0)10 7035829
Email: [email protected]
Last Name: Alejandra Mendez Romero, MD, PhD
Role: Principal Investigator

Location Countries

Country

Netherlands


Verification Date

2017-10-01

Lastchanged Date

2017-10-05

Firstreceived Date

2017-09-26

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

Erasmus Medical Center

Investigator Full Name

Alejandra Mendez Romero

Investigator Title

A. Méndez Romero MD, PhD


Keywords


Has Expanded Access

No

Condition Browse


Number Of Arms

1

Arm Group

Arm Group Label

Stereotactic body radiation therapy

Arm Group Type

Experimental


Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Merel Koedijk, MD

Phone

+31 (0)10 7041335

Email



Acronym

STRONG

Firstreceived Results Disposition Date

N/A

Study Design Info

Intervention Model

Single Group Assignment

Primary Purpose

Treatment

Masking

None (Open Label)


Study First Submitted

September 26, 2017

Study First Submitted Qc

October 5, 2017

Study First Posted

October 11, 2017

Last Update Submitted

October 5, 2017

Last Update Submitted Qc

October 5, 2017

Last Update Posted

October 11, 2017


ClinicalTrials.gov processed this data on October 11, 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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