Hepatopulmonary Radio-sterilization With Immunotherapy

NCT06053996 | Not Yet Recruiting FDA Device

• 1 other identifier: SHEBA-23-0497-OM-CTIL
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

In this protocol the investigators aim to overcome hepatic-pulmonary metastases-induced resistance to immunotherapy through high dose radiation therapy (SBRT) targeted to the metastases themselves, aiming, when possible, to ablate all macroscopic disease in these organs.

Conditions

Colon Cancer; Liver Metastasis Colon Cancer; Rectal Cancer

Keywords

radiation; radiotherapy; SBRT; immunotherapy; Stereotactic ablative radiotherapy (SABR)

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Safety and tolerability

  2 years

Secondary Outcomes (2)

• 6 month PFS

  6 months

• Overall survival (OS)

  4 years

Study Arms (2)

MSI-H mCRC

EXPERIMENTAL

high dose radiation therapy (SBRT) targeted to the lung and liver metastases

Radiation: Hepatopulmonary radio-sterilization

MSS mCRC.

EXPERIMENTAL

high dose radiation therapy (SBRT) targeted to the lung and liver metastases

Radiation: Hepatopulmonary radio-sterilization

Interventions

Hepatopulmonary radio-sterilization RADIATION

Hepatopulmonary radio-sterilization - ablation of hepatic and pulmonary metastases

MSI-H mCRC; MSS mCRC.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease factors
• Histologically- or cytologically-confirmed diagnosis of colorectal cancer (CRC).
• Metastatic or recurrent CRC, deemed surgically or medically unresectable.
• Subjects who are candidates to receive immunotherapy, whether MSS or MSI-high.
• Subjects who have liver and / or lung metastases amenable to SBRT.
• General considerations
• Age ≥18 years.
• ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A).
• Life expectancy of ≥ 3 months
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• hemoglobin ≥ 9.0 g/dL
• total bilirubin ≤ 1.5 x ULN except subjects with Gilbert Syndrome must have a total bilirubin level \< 3.0 mg/dL).
• AST(SGOT)/ALT(SGPT) ≤2.0 × institutional upper limit of normal

You may not qualify if:

• \- Disease factors / Tumor characteristics
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
• Previous treatments and trials
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 3 weeks of the first dose of treatment.
• Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Comorbidities, medications and immune modulation agents
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with type I diabetes mellitus, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects that require intermittent use of bronchodilators or local steroids, e.g., inhaled or topical steroids, at a dose of less than the equivalent of 10mg prednisone daily, would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

Sponsors & Collaborators

• Sheba Medical Center: lead

Study Sites (1)

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Ofer Margalit, MD PhD

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hili Gnessin, BA

CONTACT

+97235307034; Hili.Gnessin@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: radiation to hepatic and pulmonary metastases

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: September 26, 2023
• Study Start: November 1, 2023
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2028
• Last Updated: September 26, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)