A Phase I Study Evaluating the Safety of Stereotactic Central Ablative Radiation Therapy (SCART) for Bulky Metastatic or Recurrent Cancer

NCT ID: NCT04881981

Last Updated: 2021-05-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-05

Study Completion Date

2022-05-05

Brief Summary

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We aim to evaluate the feasibility and toxicity of testing the tolerance and immunogenic effects of high-dose SCART radiotherapy in patients with bulky metastatic or recurrent cancer in the setting of a single-arm phase I clinical trial.

The primary endpoint of the study was to determine dose-limiting toxicities (DLT)s and the Maximum Tolerated Dose (MTD) of SCART to bulky metastatic or recurrent cancers.

Detailed Description

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Despite advances in screening and surveillance, patients continue to present with both bulky primary and metastatic tumors. Some patients presented with recurrent bulky cancer in prior treated radiation fields. Spatially Fractionated Radiation therapy (SFRT) has a history of over 100 years. The principle of SFRT is distinctive from the standard radiation approaches, as it treats the total tumor with a non-uniform dose, effectively treating the tumor while staying within normal tissue tolerance of the surrounding structures. Historically, SFRT is frequently used to treat bulky malignant tumors with a high radiation dose in the stereotactic radiosurgery (SRS)/stereotactic body radiotherapy (SBRT) dose range (10-20 Gy per fraction) using megavoltage x-ray beams. The application of SFRT, historically known as GRID therapy, has produced dramatic relief of severe symptoms, significant objective regression, above average local control rates and minimal toxicity in palliative settings.

High-dose GRID radiotherapy, sometimes termed spatially-fractionated GRID radiotherapy (SFGRT), is a treatment modality that was introduced in 1909 and commonly used through the 1930's . In 1909, Kohler in Germany described radiation delivered through a perforated screen with regularly spaced blocked areas that created an effect similar to treatment with multiple small pencil beams. This spatially fractionated radiation, in contradistinction to current approaches, does not attempt to treat the total tumor volume with a uniform dose. Instead, this technique allows the delivery of high doses of radiation in clusters of small areas without producing prohibitive normal tissue damage to skin and subcutaneous tissues. In its early applications, two-dimensional grid fields were used, typically with orthovoltage beams. The grids were usually composed of open/shield circular or square shapes ranging in size from 0.5 to 1.5 cm. The application was mainly for the treatment of advanced bulky tumors.

However, the technique of GRID radiotherapy has not evolved significantly since its inception in the early 1900's, and is not the optimal method of delivering spatially fractionated radiation in the modern era. GRID has the limitation of delivering relatively high doses of radiation to normal tissues, depending on tumor location, as it is delivered via a single beam that must pass through normal tissues to reach its target. Most importantly, the highest-dose regions of the grid are superficial, and often are outside of the tumor target itself.

The basic principle of the LATTICE Radiotherapy (LRT) is to create within tumor volume multiple localized high-dose islands (12 Gy and higher) with a certain degree of separation to form low dose regions (3 Gy or lower). In an extreme case, one or two focused dose islands could be introduced in a small tumor.

Modern radiotherapy methods are readily available to deliver 3D high-dose LATTICE radiotherapy with superior dosimetry compared to the 2D GRID technique . An array of focused high-dose volumes, in essence a lattice of doses in 3D, can be generated through modern techniques resulting in highly heterogeneous dose distributions within the tumor volume, leaving adjacent and peripheral normal tissue minimally exposed.

Similar to the core principles and concepts of LRT, SCART aims to stereotactically irradiate part of target volume (hotspot) located at the center of a large tumor target with an ablative dose (15Gy or higher) and the dose quickly falls off from the edge of hotspot to low dose (3Gy or lower) at the edge of tumor volume. The goal is to irradiate as large a volume as possible with ablative dose, while maintaining the dose to the border of the tumor at low dose.

SCART is a different approach which pursuits not only the dose escalation but also the idea of facilitating or promoting intra-tumoral bystander effect, thus increasing the biological effectiveness of the treatment. Published data reviewed by Peters, et al. strongly suggest that GRID therapy induces a rapid and higher rate of tumor cell apoptosis in bulky and hypoxic tumors. This technique is very appealing to treat patients with voluminous gynecological tumors.

These makes SCART Radiotherapy a practically achievable alternative to traditional GRID therapy and LATTICE, which delivers a highly heterogeneous dose distribution, anticipated to trigger the bystander effect of radiation. With high dose regions strictly contained within the target volume, normal tissue toxicity is practically avoided providing an increased therapeutic ratio.

SCART is a promising tool to achieve dose escalation which will lead to a higher local control without adding any extra toxicity in the peripheral normal tissue regions.

Conditions

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Malignant Neoplasms

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

3+3 phase one trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SCART Arm

Single Arm patients will be treated with SCART to different dose levels.

Group Type EXPERIMENTAL

SCART radiation therapy

Intervention Type RADIATION

We will deliver high dose radiation therapy using SCART method. Beam energies of 6Mv will be used. The high dose SCART therapy will be delivered using LINAC systems, as available and appropriate for each patient. The treatment plan used for each patient will be based on an analysis of the volumetric dose including DVH analyses of the PTV and critical normal structures.

Interventions

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SCART radiation therapy

We will deliver high dose radiation therapy using SCART method. Beam energies of 6Mv will be used. The high dose SCART therapy will be delivered using LINAC systems, as available and appropriate for each patient. The treatment plan used for each patient will be based on an analysis of the volumetric dose including DVH analyses of the PTV and critical normal structures.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

3.1.1 Patients must have a history of histologically confirmed metastatic or recurrent cancers.

3.1.2 Patients must have measurable disease documented by CT and/or PET that is amenable for SCART radiation with the shortest axis of 3 cm or longer.

3.1.3 Patients must be 18 years of age or older, as this is not a pediatric protocol. There is no maximum age restriction.

3.1.4 Patients must have a life expectancy of at least 6 months in order for the study endpoints to be evaluable.

3.1.5 Patients must have a Zubrod/GOG performance status of 0 or 1.

3.1.6 Patients must have normal organ and marrow function as defined below: leukocyte\>3,000/m l absolute neutrophil count \>1,500/m l platelets \>100,000/m l bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) 2.5 X institutional upper limit of normal Creatinine within normal institutional limits OR; Creatinine clearance \> 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

3.1.7 Women of child-bearing potential will be asked to use adequate contraception.

3.1.8 Patients must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

3.2.1 Women who are pregnant or breastfeeding will be excluded.

3.2.2 Patients must not have any co-morbidity with life expectancy ≤ 6 months, or any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

3.2.3 Patients must not have active Crohn's disease or inflammatory bowel disease (IBD).

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Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Drexel University

OTHER

Sponsor Role collaborator

Innovative Institute

UNKNOWN

Sponsor Role collaborator

University of Kentucky

OTHER

Sponsor Role collaborator

Foshan Chancheng Hospital

UNKNOWN

Sponsor Role collaborator

Baptist Health, Louisville

OTHER

Sponsor Role lead

Responsible Party

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Weisi Yan

Medical Director, Baptist Corbin Radiation Oncology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Innovative Cancer Institute

Miami, Florida, United States

Site Status

Baptist health

Corbin, Kentucky, United States

Site Status

University of Kentucky Morehead Cancer Treatment Center

Morehead, Kentucky, United States

Site Status

Foshan Chancheng Hospital

Foshan, Guangdong, China

Site Status

Countries

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United States China

Central Contacts

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Weisi Yan, M.D.,Ph.D.

Role: CONTACT

1-646-763-2973

XiaoDong Wu, Ph.D.

Role: CONTACT

1-305-775-0333

Facility Contacts

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Xiaodong Wu, Ph.D.

Role: primary

Weisi Yan, M.D.,Ph.D.

Role: primary

646-763-2973

Waleed Mourad, M.D.,Ph.D.

Role: primary

606-784-3443

Jun Yang, Ph.D.

Role: primary

3057930868

QIuxia Lu, M.D.

Role: backup

References

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Yan W, Khan MK, Wu X, Simone CB 2nd, Fan J, Gressen E, Zhang X, Limoli CL, Bahig H, Tubin S, Mourad WF. Spatially fractionated radiation therapy: History, present and the future. Clin Transl Radiat Oncol. 2019 Oct 22;20:30-38. doi: 10.1016/j.ctro.2019.10.004. eCollection 2020 Jan. No abstract available.

Reference Type BACKGROUND
PMID: 31768424 (View on PubMed)

Jiang L, Li X, Zhang J, Li W, Dong F, Chen C, Lin Q, Zhang C, Zheng F, Yan W, Zheng Y, Wu X, Xu B. Combined High-Dose LATTICE Radiation Therapy and Immune Checkpoint Blockade for Advanced Bulky Tumors: The Concept and a Case Report. Front Oncol. 2021 Feb 12;10:548132. doi: 10.3389/fonc.2020.548132. eCollection 2020.

Reference Type BACKGROUND
PMID: 33643893 (View on PubMed)

Related Links

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Other Identifiers

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INT-SCART-001

Identifier Type: -

Identifier Source: org_study_id

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