Using radiation therapy to treat metastatic cancer after immunotherapy failure

Phase II Trial of Salvage Radiation Therapy to Induce Systemic Disease Regression After Progression on Systemic Immunotherapy

This study is testing if radiation therapy can help people with metastatic cancer whose condition got worse after immunotherapy, by looking at different types of radiation and how well they work.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 230 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: immunotherapy, radiation
• Locations: 5 sites (Conroe, Texas and 4 other locations)
• Trial ID: NCT02710253 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness and side effects of radiation therapy in patients whose metastatic cancer has progressed after receiving immunotherapy. The study aims to determine the optimal radiation dosage and assess the rate of systemic disease control following treatment. Patients will receive either stereotactic body radiation therapy (SBRT) or external beam radiation therapy (EBRT) based on their specific needs. The trial also evaluates the frequency of treatment-related toxicities and overall survival rates among participants.

Who should consider this trial

Good fit: Ideal candidates include adults with confirmed metastatic cancer that has progressed after immunotherapy and who have at least one site of disease suitable for radiation.

Not a fit: Patients who have not received prior immunotherapy or those with no amenable metastatic lesions for radiation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with metastatic cancer who have not responded to immunotherapy.

How similar studies have performed: Other studies have shown promising results with radiation therapy following immunotherapy, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Pathologically confirmed diagnosis of cancer.
2. Progressive disease via irRC on prior study or standard of care therapy utilizing an immunotherapy agent OR a clinical status that requires salvage radiation treatment (e.g.: palliative RT) at the discretion of treating Physician and/or PI.
3. Previous progression of disease while on treatment of an immunotherapy agent or cell-based therapy.

   a. Patients may continue with maintenance immunotherapy as part of standard of care therapy while receiving radiation.
4. Have at least one site of metastatic disease amenable to radiation. All lesions amenable to radiation may be irradiated at the discretion of treating Radiation Oncologist, depending on the location, size and number of lesions.
5. Be willing and able to provide written informed consent-for the trial.
6. Be ≥ 18 years of age on day of signing informed consent.
7. Have a performance status of 0-2 on the ECOG performance scale.
8. Female subject of childbearing potential should have a negative urine or serum pregnancy within 28 days prior to first fraction of radiation.

   \- Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
9. We will allow prior radiation to other sites, with no washout period, prior to study entry as long as the high dose regions of the prior and proposed radiation fields do not overlap or it can overlap, as long as the area being treated is getting low dose radiation; this can be done alone or in combination with high dose to a previously un-irradiated area.
10. Non-English speakers may enroll on the protocol.

Exclusion Criteria:

The subject must be excluded from participating in the trial if the subject:

1. Has a diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy.
2. Has had prior radiation therapy within the past 3 months where the high dose area of the prior radiation would overlap with the high dose area of the intended radiation based on the judgment of the treating radiation oncologist.
3. Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previous treatment.

   * Note: Subjects with permanent ≤ Grade 2 toxicities (e.g. neuropathy) or toxicities corrected through routine medical management (e.g. thyroid replacement for hypothyroidisim) are an exception to this criterion and may qualify for the study.
   * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
   * Note: Subjects with asymptomatic ≤ Grade 2 laboratory or dermatologic abnormalities are an exception to this criterion and may qualify for the study pending the judgment of the treating radiation oncologist.
4. Has an active infection requiring intravenous systemic therapy or hospital admission.
5. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
6. Is pregnant or expecting to conceive or within the projected duration of the trial, starting with the screening visit through 60 days after the last fraction of radiation.

Where this trial is running

Conroe, Texas and 4 other locations

• MD Anderson in The Woodlands — Conroe, Texas, United States (Recruiting)
• M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• MD Anderson West Houston — Houston, Texas, United States (Recruiting)
• MD Anderson League City — League City, Texas, United States (Recruiting)
• MD Anderson in Sugar Land — Sugar Land, Texas, United States (Recruiting)

Study contacts

• Principal investigator: James Welsh — M.D. Anderson Cancer Center
• Study coordinator: James Welsh, MD

Conditions Hematopoietic and Lymphoid Cell Neoplasm; Metastatic Malignant Solid Neoplasm