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Methionine-Restricted Diet to Potentiate The Effects of Radiation Therapy

Primary Purpose

Cancer, Lung Cancer, Prostate Cancer

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Methionine-restricted diet
Sponsored by
West Virginia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Men and women over age 18
  • Any non-skin cancer malignancy to be treated with standard of care, curative-intent, radiation therapy with an RT course of 6 weeks or less, without concurrently administered cytotoxic chemotherapy. Patients with oligometastatic disease being treated with local consolidative radiation therapy are also eligible. Pathologic confirmation of malignancy is not required if the treating physician(s) agree that this lesion is highly likely to be malignant and the patient elects to forego biopsy.
  • The RT plan must achieve standard normal tissue dose-volume constraints.
  • Zubrod Performance status 0-2
  • Adequate organ and marrow function (leukocytes ≥ 2,000/μL, platelets ≥ 50,000/μL, hemoglobin > 8.0 g/dL, total bilirubin ≤ 3 X ULN, AST(SGOT)/ALT(SPGT) ≤ 3 X ULN, albumin > 2.0 g/dL, calcium < 10.5 mg/dL, creatinine ≤ 3 X ULN)
  • Negative serum or urine pregnancy test within 72 hours prior to registration for women of childbearing potential
  • Women of childbearing potential and male participants must agree to use a medically effective means of birth control, such as condom/diaphragm and spermicidal foam, intrauterine device (IUD), or prescription birth control pills, throughout their participation in the treatment phase of the study.
  • Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  • Prior radiation therapy that would result in overlap of radiation fields.
  • Unintentional weight loss of >10% of normal body weight over a period of 6 months or less.
  • Use of an appetite stimulant in the past 6 months for unintentional weight loss.
  • Allergy to soy (an ingredient in both methionine-free medical food supplements).
  • Administration of cytotoxic chemotherapy within 4 weeks prior to initiation of the study treatment.
  • Use of ongoing biologic/targeted/immune/hormonal therapy will be permitted.
  • There should be no intention for the patient to receive other local therapy (radiotherapy and/or surgery) or cytotoxic chemotherapy within 4 weeks after completion of the study treatment
  • Active systemic, pulmonary, or pericardial infection.
  • Psychiatric illness/social situations that would limit compliance with study requirements. * - Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus

Sites / Locations

  • WVU Cancer Institute - Mary Babb Randolph Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Methionine-restricted diet

Arm Description

6-10 weeks methionine-restricted diet (MRD) curative intent radiation therapy course of 6 weeks or less.

Outcomes

Primary Outcome Measures

Safety of combined MRD plus RT will be assessed by measuring the rate of 1-year grade 3 or higher adverse events definitely, probably, or possibly related to MRD and RT, using CTCAE version 5.0.
The expected cumulative rate of grade 3-5 toxicity is less than 15%

Secondary Outcome Measures

Patient adherence to the MRD will be assessed by measuring plasma methionine levels 2 weeks and 6 weeks after starting the MRD
Plasma methionine levels less than 13 uM will be considered compliant

Full Information

First Posted
June 15, 2018
Last Updated
April 24, 2023
Sponsor
West Virginia University
Collaborators
West Virginia Clinical and Translational Science Institute
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1. Study Identification

Unique Protocol Identification Number
NCT03574194
Brief Title
Methionine-Restricted Diet to Potentiate The Effects of Radiation Therapy
Official Title
Methionine-Restricted Diet to Potentiate The Effects of Radiation Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Terminated
Why Stopped
Suspended due to COVID-19 pandemic
Study Start Date
June 12, 2018 (Actual)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
December 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
West Virginia University
Collaborators
West Virginia Clinical and Translational Science Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A diet consisting of a reduced quantity of the essential amino acid methionine sensitizes cancer cells to radiation therapy and reduces metastasis formation and disease progression in mice. However, to date, dietary restriction of methionine has not been tested in combination with radiation therapy in humans as a strategy to improve patient outcomes.
Detailed Description
Radiation therapy (RT) is often given concurrently with systemic chemotherapy in order to sensitize the cancer cells to radiation and increase local and regional disease control. However, chemotherapy is often associated with significant toxicity and many patients cannot tolerate it. As such, exploring alternative approaches to radiosensitization that may be more tolerable for patients is important. One innovative strategy that has potential to enhance both the safety and efficacy of SBRT is a methionine-restricted diet (MRD) as an adjunct to radiation therapy. While normal cells can tolerate some degree of methionine deficiency, the vast majority of cancer cells are methionine auxotrophs that require dietary intake of methionine. In the absence of methionine, cancer cells undergo cell cycle arrest and cell death. Preclinical data suggests that consuming a reduced quantity of methionine sensitizes cancer cells to radiation therapy and reduces metastasis formation and disease progression in mice; Phase 1 clinical trials have also demonstrated the safety of the diet with and without concurrent chemotherapy; however, dietary restriction of methionine has not been tested in combination with radiation therapy in humans. This protocol will test our hypothesis that a MRD will be a safe addition to radiation therapy for a variety of human malignancies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Lung Cancer, Prostate Cancer, Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
6-10 weeks methionine-restricted diet (MRD) with standard of care curative-intent radiation therapy (6 week course or less), without concurrent chemotherapy
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methionine-restricted diet
Arm Type
Experimental
Arm Description
6-10 weeks methionine-restricted diet (MRD) curative intent radiation therapy course of 6 weeks or less.
Intervention Type
Dietary Supplement
Intervention Name(s)
Methionine-restricted diet
Intervention Description
The methionine-restricted diet diet (MRD) will begin 2 weeks prior to radiation therapy to deplete methionine stores in the body, continue during radiation, and extend for approximately 2 weeks after the last radiation fraction for a total of 6-10 weeks (depending on duration of radiation course).
Primary Outcome Measure Information:
Title
Safety of combined MRD plus RT will be assessed by measuring the rate of 1-year grade 3 or higher adverse events definitely, probably, or possibly related to MRD and RT, using CTCAE version 5.0.
Description
The expected cumulative rate of grade 3-5 toxicity is less than 15%
Time Frame
One year from the start of methionine-restricted diet (MRD)
Secondary Outcome Measure Information:
Title
Patient adherence to the MRD will be assessed by measuring plasma methionine levels 2 weeks and 6 weeks after starting the MRD
Description
Plasma methionine levels less than 13 uM will be considered compliant
Time Frame
Measurements will be done 2 weeks and 6 weeks after starting the MRD

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women over age 18 Any non-skin cancer malignancy to be treated with standard of care, curative-intent, radiation therapy with an RT course of 6 weeks or less, without concurrently administered cytotoxic chemotherapy. Patients with oligometastatic disease being treated with local consolidative radiation therapy are also eligible. Pathologic confirmation of malignancy is not required if the treating physician(s) agree that this lesion is highly likely to be malignant and the patient elects to forego biopsy. The RT plan must achieve standard normal tissue dose-volume constraints. Zubrod Performance status 0-2 Adequate organ and marrow function (leukocytes ≥ 2,000/μL, platelets ≥ 50,000/μL, hemoglobin > 8.0 g/dL, total bilirubin ≤ 3 X ULN, AST(SGOT)/ALT(SPGT) ≤ 3 X ULN, albumin > 2.0 g/dL, calcium < 10.5 mg/dL, creatinine ≤ 3 X ULN) Negative serum or urine pregnancy test within 72 hours prior to registration for women of childbearing potential Women of childbearing potential and male participants must agree to use a medically effective means of birth control, such as condom/diaphragm and spermicidal foam, intrauterine device (IUD), or prescription birth control pills, throughout their participation in the treatment phase of the study. Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: Prior radiation therapy that would result in overlap of radiation fields. Unintentional weight loss of >10% of normal body weight over a period of 6 months or less. Use of an appetite stimulant in the past 6 months for unintentional weight loss. Allergy to soy (an ingredient in both methionine-free medical food supplements). Administration of cytotoxic chemotherapy within 4 weeks prior to initiation of the study treatment. Use of ongoing biologic/targeted/immune/hormonal therapy will be permitted. There should be no intention for the patient to receive other local therapy (radiotherapy and/or surgery) or cytotoxic chemotherapy within 4 weeks after completion of the study treatment Active systemic, pulmonary, or pericardial infection. Psychiatric illness/social situations that would limit compliance with study requirements. * - Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joshua Weir, MD
Organizational Affiliation
West Virginia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
WVU Cancer Institute - Mary Babb Randolph Cancer Center
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Methionine-Restricted Diet to Potentiate The Effects of Radiation Therapy

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