Colon CancerTROS-8NCT06053996
Hepatopulmonary Radio-sterilization With Immunotherapy
A study testing Hepatopulmonary radio-sterilization in people with Colon Cancer and Liver Metastasis Colon Cancer, run by Sheba Medical Center at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer, Liver Metastasis Colon Cancer, Rectal Cancer
- What is being tested?
- Hepatopulmonary radio-sterilization
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Nov 2023to 30 Aug 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 mL/min (using the Cockcroft Gault formula)
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of treatment.
- Signed Written Informed Consent
- Subjects must have signed and dated an IRB approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
- Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
Who cannot join
- 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.
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- 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.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
- Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
- History of allergy or hypersensitivity to any study drug components, to compounds of similar chemical or biologic composition
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site
Sheba Medical Center
Ramat Gan, 52621
Ofer Margalit, MD PhD, 972-3-5305338, ofer.margalit@sheba.health.gov.il
yaacov lawrence, MD, 0526669145, yaacov.lawrence@sheba.health.gov.il
About this study
Official title: Hepatopulmonary Radio-sterilization Combined With Checkpoint Inhibition, a Proof-of-concept Phase II Clinical Trial in Colorectal Cancer
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.
Read the detailed description
A number of recent reports have noted the relative resistance of liver metastases to immunotherapy across a range of cancer types1,2, including mCRC. In two studies of MSS mCRC using a combination of PD-1 and CTLA-4 inhibitors there was a marked difference in response rate between subjects with and without liver metastases, 0% vs 42% in the study of Bullock et al3, and 0% versus 36% in the study by Fakih et al4. The proposed mechanism is a macrophage-induced T cell death occurring within hepatic metastases, leading to systemic imunosupression5. Furthermore, these investigators demonstrated that in preclinical models of MSS mCRC, liver-metastasis directed radiotherapy eliminates immunosuppressive hepatic macrophages, increases hepatic T cell survival and reduces hepatic siphoning of T cells, thereby abolishing the immunotherapy resistance induced by liver metastasis5. Conversely, liver irradiation in the absence of metastases was ineffective5.
Similarly, in microsatellite instability high mCRC the presence of liver metastases is associated with a poor response to immunotherapy6. In a retrospective analysis of 161 MSI High mCRC patients treated with immunotherapy, pooling data from MD Anderson and Sheba, the presence of liver and lung metastases was associated with a reduced PFS, with a HR of 2.6 and 2.4, respectively (submitted for publication).
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
- Being tested
- Hepatopulmonary radio-sterilization
- Keywords
- radiation, radiotherapy, SBRT, immunotherapy, Stereotactic ablative radiotherapy (SABR)
- Medical subject headings
- Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hepatopulmonary radio-sterilizationRadiation
Hepatopulmonary radio-sterilization - ablation of hepatic and pulmonary metastases
| Study group | Role | What they receive |
|---|---|---|
| MSI-H mCRC | Experimental | high dose radiation therapy (SBRT) targeted to the lung and liver metastases Receives: Radiation: Hepatopulmonary radio-sterilization |
| MSS mCRC. | Experimental | high dose radiation therapy (SBRT) targeted to the lung and liver metastases Receives: Radiation: Hepatopulmonary radio-sterilization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Safety and tolerability
Measured: 2 years
Secondary outcomes (2)
6 month PFS
progression free survival at 6 months
Measured: 6 months
Overall survival (OS)
Overall survival (OS)
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2023
- Study start1 Nov 2023 (estimated)
- Primary completion30 Aug 2027 (estimated)
- Study completion30 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- radiation to hepatic and pulmonary metastases
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Ofer Margalit, MD PhD, Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06053996
- Sponsor's protocol ID
- SHEBA-23-0497-OM-CTIL
- Acronym
- TROS-8
- Status last verified
- Sep 2023
- First submitted
- 7 Aug 2023
- Last updated
- 26 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatopulmonary Radio-sterilization Combined With Checkpoint Inhibition, a Proof-of-concept Phase II Clinical Trial in Colorectal Cancer
- ClinicalTrials.gov ID
- NCT06053996
- Acronym / sponsor ID
- TROS-8 / SHEBA-23-0497-OM-CTIL
- Conditions
- Colon Cancer, Liver Metastasis Colon Cancer, Rectal Cancer
- Keywords
- radiation, radiotherapy, SBRT, immunotherapy, Stereotactic ablative radiotherapy (SABR)
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 1 Nov 2023 (estimated)
- Primary completion
- 30 Aug 2027 (estimated)
- Study completion
- 30 Aug 2028 (estimated)
- First posted
- 26 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A number of recent reports have noted the relative resistance of liver metastases to immunotherapy across a range of cancer types1,2, including mCRC. In two studies of MSS mCRC using a combination of PD-1 and CTLA-4 inhibitors there was a marked difference in response rate between subjects with and without liver metastases, 0% vs 42% in the study of Bullock et al3, and 0% versus 36% in the study by Fakih et al4. The proposed mechanism is a macrophage-induced T cell death occurring within hepatic metastases, leading to systemic imunosupression5. Furthermore, these investigators demonstrated that in preclinical models of MSS mCRC, liver-metastasis directed radiotherapy eliminates immunosuppressive hepatic macrophages, increases hepatic T cell survival and reduces hepatic siphoning of T cells, thereby abolishing the immunotherapy resistance induced by liver metastasis5. Conversely, liver irradiation in the absence of metastases was ineffective5.
Similarly, in microsatellite instability high mCRC the presence of liver metastases is associated with a poor response to immunotherapy6. In a retrospective analysis of 161 MSI High mCRC patients treated with immunotherapy, pooling data from MD Anderson and Sheba, the presence of liver and lung metastases was associated with a reduced PFS, with a HR of 2.6 and 2.4, respectively (submitted for publication).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- radiation to hepatic and pulmonary metastases
| Arm | Type | Receives |
|---|---|---|
| MSI-H mCRC | Experimental | Radiation: Hepatopulmonary radio-sterilizationhigh dose radiation therapy (SBRT) targeted to the lung and liver metastases |
| MSS mCRC. | Experimental | Radiation: Hepatopulmonary radio-sterilizationhigh dose radiation therapy (SBRT) targeted to the lung and liver metastases |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hepatopulmonary radio-sterilizationHepatopulmonary radio-sterilization - ablation of hepatic and pulmonary metastases | Radiation | MSI-H mCRC, MSS mCRC. |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: 2 years
Safety and tolerability
2 secondary outcomes
6 month PFS
Time frame: 6 months
Overall survival (OS)
Time frame: 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ofer Margalit, MD PhD principal investigator
Sheba Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hepatopulmonary radio-sterilization in people with Colon Cancer and Liver Metastasis Colon Cancer, run by Sheba Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 26 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hili Gnessin, BA (+97235307034, Hili.Gnessin@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2023.