Liver CancerPhase 1NCT02239900
Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) in Advanced Solid Tumors
A Phase 1 study testing Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) in people with Liver Cancer and Lung Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the highest tolerable dose of ipilimumab and stereotactic body radiation therapy (SBRT). The safety and effectiveness of these treatments given consecutively will also be studied. This is an investigational study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cancer, Lung Cancer
- What is being tested?
- Ipilimumab and Stereotactic Body Radiation Therapy (SBRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Aug 2014to 25 Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Patients must have histological confirmation of metastatic cancer with at least one metastatic or primary lesion in the liver, lung, or adrenal gland.
- Patients who have completed previous systemic therapies 5 drug half-lives or 4-weeks prior to enrollment on study, whichever is shorter. Note: patients with anaplastic thyroid will be waived from this inclusion criteria given the rapid trajectory of their disease.
- All patients must have at least one metastatic or primary lesion within the lung or liver located in an anatomical location amenable to SBRT treatment with 50 Gy in 4 fractions, or if not, with either a lung, liver, or adrenal lesion treatable to 60 Gy in 10 fractions.
- Repeat radiation in fields previously radiated will be allowed at the discretion of the treating physician.
- Age >/= 18 years
- ECOG performance status </=2 (Karnofsky >60%).
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- Patients must have normal organ and marrow function as defined below: * Total bilirubin </= 2.0 mg/dL. (Does NOT apply to patients with Gilbert's Syndrome) * Aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Alanine Aminotransferase (ALT) Serum Glutamic-Pyruvic Transaminase (SGPT) <2.5 X institutional upper limit of normal (patients with liver involvement will be allowed </= 5.0 X institutional upper normal limit) *WBC >/= 2500/uL, ANC >/= 1000/uL *Platelets >/= 75K *Hemoglobin >/= 9g/dL *Creatinine </= 2.0 x ULN
- Patients must be willing and able to review, understand, and provide written consent before starting therapy.
- Patients with brain metastasis will be included as long as they are free of neurologic symptoms related to metastatic brain lesions and who do not require or receive systemic corticosteroid therapy in the 14 days prior to beginning ipilimumab therapy
- Patients that have previously progressed on immunotherapy such as ipilimumab will be eligible.
Who cannot join
- Serious autoimmune disease at the discretion of the treating attending: Patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this study.
- Active diverticulitis, intra-abdominal abscess, Gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of Adverse Events: (AE's) e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Known active HIV, Hepatitis B, or Hepatitis C that has not been documented to be cured.
- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).
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- Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids while receiving ipilimumab (as long as steroid replacement is significantly greater than what is required for physiologic replacement, i.e. in hypothyroidism).
- Pregnant women are excluded from this study. Women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. Acceptable forms of birth control include: Birth control pills plus a barrier method, such as a condom or diaphragm, Intrauterine devices (IUD) plus a barrier method, Implantable or injectable birth control (such as NorplantR or epo-ProveraR) started at least 3 months before joining the study, plus a barrier method, or Double-barrier method, such as a condom when used in combination with a diaphragm. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician.
- History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.
- Prior allogeneic stem cell transplantation
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase I/II Trial of Ipilimumab (Immunotherapy) and Hypofractionated Stereotactic Radiation Therapy in Patients With Advanced Solid Malignancies
The goal of this clinical research study is to find the highest tolerable dose of ipilimumab and stereotactic body radiation therapy (SBRT). The safety and effectiveness of these treatments given consecutively will also be studied.
This is an investigational study. SBRT is FDA approved for the control of metastatic and primary tumors. Ipilimumab is FDA approved and commercially available for the treatment of metastatic melanoma that cannot be removed with surgery. The use of SBRT with ipilimumab is investigational. The study doctor can explain how the study drug is designed to work.
Up to 120 participants will be enrolled in this study. All will take part at MD Anderson.
Read the detailed description
Study Groups:
Participants on this study are enrolled into Phase 1 (Dose De-Escalation, or Dose-Finding) or Phase 2 (Dose Expansion), based on when they join the study.
Phase 1: Dose De-Escalation:
If you are found to be eligible to take part in this study, you will be assigned to 1 of 5 groups based on the type of disease you have.
- If you are in Groups 1 or 3, you will receive SBRT and 1 dose of ipilimumab within a few days after your SBRT treatment, and then you will receive 3 more doses of ipilimumab.
- If you are in Groups 2, 4, or 5, you will receive 2 doses of ipilimumab, SBRT, and then 2 more doses of ipilimumab.
If you are in Group 5, SBRT will be given over a longer period of time (more days or weeks).
All participants will receive the same dose level of ipilimumab.
You will be given a separate consent form explaining SBRT and its risks.
In each group, 3 participants will be enrolled at the first dose level. If no more than 1 participant has intolerable side effects, up to 3 more participants will be enrolled at that dose level. If no intolerable side effects are seen at that dose level, that is considered the highest tolerated dose.
If enough intolerable side effects are seen at the assigned dose level, the total dose amount of radiation given in any group may be lowered up to 2 times.
Phase 2: Dose Expansion:
Once the highest tolerated dose combination is found in each study group, up to 14 more participants will be enrolled at that dose level combination in each group.
Study Drug Administration:
Each study cycle is 21 days.
If you are in Groups 1 or 3 (early ipilimumab and SBRT), you will receive ipilimumab by vein over about 90 minutes on Day 1 of all cycles. You will also receive SBRT over about 30-45 minutes on Days 1-4 of Cycle 1.
If you are in Groups 2 or 4 (late ipilimumab and SBRT), you will receive ipilimumab by vein over about 90 minutes on Day 1 of Cycles 1 and 2 and then SBRT on Days 29-33. After your SBRT treatment, you will take ipilimumab on Day 1 of Cycles 3 and 4.
If you are in Group 5 (late ipilimumab and SBRT), you will receive ipilimumab on Day 1 of Cycle 1 and SBRT over about 30-45 minutes on Days 1-5 and Days 9-12 of Cycle 1. After your SBRT treatment, you will take ipilimumab on Day 1 of Cycles 2-4.
You will be given standard drugs to help decrease the risk of side effects and to help support your immune system. You may ask the study staff for information about how the drugs are given and their risks.
Study Visits:
During Week 1 of all cycles and Week 2 of Cycle 2:
- You will have a physical exam, including measurement of your weight.
- Blood (about 1 tablespoon) will be drawn for routine tests.
During Week 3 of Cycles 2 and 4, you will have an MRI, CT scan, and/or PET/CT scan to check the status of the disease.
If you are in Phase 2, during Week 3 of each cycle, blood (about 2 teaspoons) may be drawn for biomarker testing, if the doctor thinks it is safe.
You may have a chest scan if the doctor thinks it is needed.
Length of Study:
You may receive up to 4 cycles of treatment with ipilimumab and SBRT. About 8 weeks after you have completed Cycle 4, if the size of the tumor does not change or it gets smaller while you are receiving therapy, you may be able to continue to receive ipilimumab and/or radiation. The study doctor will discuss this option with you.
You will no longer be able to receive treatment if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after you have completed the follow-up visits.
Follow-Up:
About 30 days after your last dose of ipilimumab and then every 3 months after that for up to 2 years, you will come to the clinic for follow-up visits. At these visits:
- You will have a physical exam, including measurement of your weight..
- Blood (about 1 tablespoon) be drawn for routine tests.
- Blood (about 2 teaspoons) may be drawn for biomarker testing, if the doctor thinks it is safe.
- Urine will be collected for routine tests.
- You will have an MRI, CT scan, and/or PET/CT scan to check the status of the disease.
- Conditions
- Liver Cancer, Lung Cancer
- Being tested
- Ipilimumab, Stereotactic Body Radiation Therapy (SBRT)
- Keywords
- Liver Cancer, Lung Cancer, Adrenal Gland, Metastasis, Advanced Solid Malignancies, Ipilimumab, Yervoy, BMS-734016, MDX010, Stereotactic Body Radiation Therapy, SBRT, XRT
- Medical subject headings
- Liver Neoplasms, Lung Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called Yervoy, BMS-734016, MDX010
Treatment Group 1 and 3: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses.
Treatment Group 2 and 4: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4.
Treatment Group 5: Ipilimumab 3 mg/kg by vein on Day 1 of Cycle 1. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 2-4
Stereotactic Body Radiation Therapy (SBRT)Radiation
Also called SBRT, XRT
Treatment Group 1 and 3: SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 1 - 4 of Cycle 1.
Treatment Group 2 and 4: SBRT 50 Gy in 4 fractions to 1-4 liver lesion(s) on Days 29 - 33 of each 21 day cycle.
Treatment Group 5: SBRT 60 Gy in 10 fractions to 1 - 4 lung, liver, or adrenal lesion (s) on Days 1 - 5 and Days 9 - 12 of Cycle 1.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 Liver: Concurrent (early) Ipilimumab and SBRT | Experimental | Participants with at least 1 liver metastasis - Treatment Group 1: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 1 - 4 of Cycle 1. Receives: Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| Group 2 Liver: Sequential (late) Ipilimumab and SBRT | Experimental | Participants with at least 1 liver metastasis - Treatment Group 2: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Each cycle is 21 days. SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 29 - 33 of each 21 day cycle. Receives: Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| Group 3 Lung: Concurrent (early) Ipilimumab and SBRT | Experimental | Participants with at least 1 lung metastasis - Treatment Group 3: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. SBRT 50 Gy in 4 fractions to 1 - 4 lung lesion(s) on Days 1 - 4 of Cycle 1. Receives: Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| Group 4 Lung: Sequential (late) Ipilimumab and SBRT | Experimental | Participants with at least 1 lung metastasis - Treatment Group 4: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Each cycle is 21 days. SBRT 50 Gy in 4 fractions to 1 - 4 lung lesion(s) on Days 29 - 33 of each 21 day cycle. Receives: Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| Group 5 Liver/Lung Metastasis: (late) Ipilimumab and SBRT | Experimental | Participants with 1 liver or lung metastasis - Treatment Group 5: Ipilimumab 3 mg/kg by vein on Day 1 of Cycle 1. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 2 - 4. Each cycle is 21 days. SBRT 60 Gy in 10 fractions to 1 - 4 lung, liver, or adrenal lesion (s) on Days 1 - 5 and Days 9 - 12 of Cycle 1. Receives: Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT) |
| Thyroid Expansion Cohort | Experimental | Participants enrolled in this arm treated to a total dose of 50 Gy in 4 fractions, 60 Gy in 10 fractions, or 20 Gy in 5 fractions with stereotactic radiotherapy to a liver or lung lesion. The choice of radiation dose will be at the discretion of the treating radiation oncologist.
Participants receive Ipilimumab every 21 days for a total of 4 doses. Receives: Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT)
MTD defined as highest dose level with less than 2 patients with dose limiting toxicity (DLT) out of at least six patients in the cohort. All enrolled participants will be considered in the DLT analysis. If at any time more than or equal to one third (33%) of participants at a dose level experience DLT, the MTD will be reassessed and the next lowest dose level for the combination therapy considered the MTD.
Measured: Third week of second, 21 day cycle
Secondary outcomes (1)
Response Rate of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT)
Response and progression evaluated using guidelines proposed by the Immune Related Response Criteria (irRC). Patients with measurable disease also assessed using standard Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and World Health Organization (WHO) treatment response criteria. Complete Response (irCR): complete disappearance of all lesions (whether measurable or not, and no new lesions) confirmation by a repeat, consecutive imaging assessment no less than 4 wk from the date first documented. Partial Response (irPR): decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive imaging assessment at least 4 wk after first documentation. Progressive Disease (irPD): increase in tumor burden ≥25% relative to nadir (minimum recorded tumor burden) confirmation by a repeat, consecutive imaging assessment no less than 4 wk from date first documented.
Measured: 30 days after last dose of Ipilimumab
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2014 (estimated)
- Study start26 Aug 2014
- Primary completion25 Oct 2019
- Study completion25 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- James Welsh, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02239900
- Sponsor's protocol ID
- 2013-0882
- Other IDs
- NCI-2015-00042
- Status last verified
- Nov 2020
- First submitted
- 11 Sep 2014
- Last updated
- 30 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
He K, Hong DS, Tang C, Sezen D, Cox L, Maleki A, Bertolet G, Nguyen QN, Comeaux NI, Schuda L, Chen D, Welsh JW. Five-year overall survival with ipilimumab and stereotactic ablative radiotherapy for metastatic disease. Radiother Oncol. 2023 Jun;183:109618. doi: 10.1016/j.radonc.2023.109618. Epub 2023 Mar 13.
PubMed 36921766Chen D, Menon H, Verma V, Guo C, Ramapriyan R, Barsoumian H, Younes A, Hu Y, Wasley M, Cortez MA, Welsh J. Response and outcomes after anti-CTLA4 versus anti-PD1 combined with stereotactic body radiation therapy for metastatic non-small cell lung cancer: retrospective analysis of two single-institution prospective trials. J Immunother Cancer. 2020 Jan;8(1):e000492. doi: 10.1136/jitc-2019-000492.
PubMed 31996395Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016 Dec 3;388(10061):2783-2795. doi: 10.1016/S0140-6736(16)30172-6. Epub 2016 May 27.
PubMed 27240885
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Ipilimumab (Immunotherapy) and Hypofractionated Stereotactic Radiation Therapy in Patients With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT02239900
- Acronym / sponsor ID
- 2013-0882
- Conditions
- Liver Cancer, Lung Cancer
- Keywords
- Liver Cancer, Lung Cancer, Adrenal Gland, Metastasis, Advanced Solid Malignancies, Ipilimumab, Yervoy, BMS-734016
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 26 Aug 2014 (actual)
- Primary completion
- 25 Oct 2019 (actual)
- Study completion
- 25 Oct 2019 (actual)
- First posted
- 15 Sep 2014 (estimated)
- 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.
The goal of this clinical research study is to find the highest tolerable dose of ipilimumab and stereotactic body radiation therapy (SBRT). The safety and effectiveness of these treatments given consecutively will also be studied.
This is an investigational study. SBRT is FDA approved for the control of metastatic and primary tumors. Ipilimumab is FDA approved and commercially available for the treatment of metastatic melanoma that cannot be removed with surgery. The use of SBRT with ipilimumab is investigational. The study doctor can explain how the study drug is designed to work.
Up to 120 participants will be enrolled in this study. All will take part at MD Anderson.
Detailed description
Study Groups:
Participants on this study are enrolled into Phase 1 (Dose De-Escalation, or Dose-Finding) or Phase 2 (Dose Expansion), based on when they join the study.
Phase 1: Dose De-Escalation:
If you are found to be eligible to take part in this study, you will be assigned to 1 of 5 groups based on the type of disease you have.
- If you are in Groups 1 or 3, you will receive SBRT and 1 dose of ipilimumab within a few days after your SBRT treatment, and then you will receive 3 more doses of ipilimumab.
- If you are in Groups 2, 4, or 5, you will receive 2 doses of ipilimumab, SBRT, and then 2 more doses of ipilimumab.
If you are in Group 5, SBRT will be given over a longer period of time (more days or weeks).
All participants will receive the same dose level of ipilimumab.
You will be given a separate consent form explaining SBRT and its risks.
In each group, 3 participants will be enrolled at the first dose level. If no more than 1 participant has intolerable side effects, up to 3 more participants will be enrolled at that dose level. If no intolerable side effects are seen at that dose level, that is considered the highest tolerated dose.
If enough intolerable side effects are seen at the assigned dose level, the total dose amount of radiation given in any group may be lowered up to 2 times.
Phase 2: Dose Expansion:
Once the highest tolerated dose combination is found in each study group, up to 14 more participants will be enrolled at that dose level combination in each group.
Study Drug Administration:
Each study cycle is 21 days.
If you are in Groups 1 or 3 (early ipilimumab and SBRT), you will receive ipilimumab by vein over about 90 minutes on Day 1 of all cycles. You will also receive SBRT over about 30-45 minutes on Days 1-4 of Cycle 1.
If you are in Groups 2 or 4 (late ipilimumab and SBRT), you will receive ipilimumab by vein over about 90 minutes on Day 1 of Cycles 1 and 2 and then SBRT on Days 29-33. After your SBRT treatment, you will take ipilimumab on Day 1 of Cycles 3 and 4.
If you are in Group 5 (late ipilimumab and SBRT), you will receive ipilimumab on Day 1 of Cycle 1 and SBRT over about 30-45 minutes on Days 1-5 and Days 9-12 of Cycle 1. After your SBRT treatment, you will take ipilimumab on Day 1 of Cycles 2-4.
You will be given standard drugs to help decrease the risk of side effects and to help support your immune system. You may ask the study staff for information about how the drugs are given and their risks.
Study Visits:
During Week 1 of all cycles and Week 2 of Cycle 2:
- You will have a physical exam, including measurement of your weight.
- Blood (about 1 tablespoon) will be drawn for routine tests.
During Week 3 of Cycles 2 and 4, you will have an MRI, CT scan, and/or PET/CT scan to check the status of the disease.
If you are in Phase 2, during Week 3 of each cycle, blood (about 2 teaspoons) may be drawn for biomarker testing, if the doctor thinks it is safe.
You may have a chest scan if the doctor thinks it is needed.
Length of Study:
You may receive up to 4 cycles of treatment with ipilimumab and SBRT. About 8 weeks after you have completed Cycle 4, if the size of the tumor does not change or it gets smaller while you are receiving therapy, you may be able to continue to receive ipilimumab and/or radiation. The study doctor will discuss this option with you.
You will no longer be able to receive treatment if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after you have completed the follow-up visits.
Follow-Up:
About 30 days after your last dose of ipilimumab and then every 3 months after that for up to 2 years, you will come to the clinic for follow-up visits. At these visits:
- You will have a physical exam, including measurement of your weight..
- Blood (about 1 tablespoon) be drawn for routine tests.
- Blood (about 2 teaspoons) may be drawn for biomarker testing, if the doctor thinks it is safe.
- Urine will be collected for routine tests.
- You will have an MRI, CT scan, and/or PET/CT scan to check the status of the disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Group 1 Liver: Concurrent (early) Ipilimumab and SBRT | Experimental | Drug: Ipilimumab, Radiation: Stereotactic Body Radiation Therapy (SBRT)Participants with at least 1 liver metastasis - Treatment Group 1: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 1 - 4 of Cycle 1. |
| Group 2 Liver: Sequential (late) Ipilimumab and SBRT | Experimental | Drug: Ipilimumab, Radiation: Stereotactic Body Radiation Therapy (SBRT)Participants with at least 1 liver metastasis - Treatment Group 2: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Each cycle is 21 days. SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 29 - 33 of each 21 day cycle. |
| Group 3 Lung: Concurrent (early) Ipilimumab and SBRT | Experimental | Drug: Ipilimumab, Radiation: Stereotactic Body Radiation Therapy (SBRT)Participants with at least 1 lung metastasis - Treatment Group 3: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. SBRT 50 Gy in 4 fractions to 1 - 4 lung lesion(s) on Days 1 - 4 of Cycle 1. |
| Group 4 Lung: Sequential (late) Ipilimumab and SBRT | Experimental | Drug: Ipilimumab, Radiation: Stereotactic Body Radiation Therapy (SBRT)Participants with at least 1 lung metastasis - Treatment Group 4: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Each cycle is 21 days. SBRT 50 Gy in 4 fractions to 1 - 4 lung lesion(s) on Days 29 - 33 of each 21 day cycle. |
| Group 5 Liver/Lung Metastasis: (late) Ipilimumab and SBRT | Experimental | Drug: Ipilimumab, Radiation: Stereotactic Body Radiation Therapy (SBRT)Participants with 1 liver or lung metastasis - Treatment Group 5: Ipilimumab 3 mg/kg by vein on Day 1 of Cycle 1. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 2 - 4. Each cycle is 21 days. SBRT 60 Gy in 10 fractions to 1 - 4 lung, liver, or adrenal lesion (s) on Days 1 - 5 and Days 9 - 12 of Cycle 1. |
| Thyroid Expansion Cohort | Experimental | Drug: Ipilimumab, Radiation: Stereotactic Body Radiation Therapy (SBRT)Participants enrolled in this arm treated to a total dose of 50 Gy in 4 fractions, 60 Gy in 10 fractions, or 20 Gy in 5 fractions with stereotactic radiotherapy to a liver or lung lesion. The choice of radiation dose will be at the discretion of the treating radiation oncologist. Participants receive Ipilimumab every 21 days for a total of 4 doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must have histological confirmation of metastatic cancer with at least one metastatic or primary lesion in the liver, lung, or adrenal gland.
- Patients who have completed previous systemic therapies 5 drug half-lives or 4-weeks prior to enrollment on study, whichever is shorter. Note: patients with anaplastic thyroid will be waived from this inclusion criteria given the rapid trajectory of their disease.
- All patients must have at least one metastatic or primary lesion within the lung or liver located in an anatomical location amenable to SBRT treatment with 50 Gy in 4 fractions, or if not, with either a lung, liver, or adrenal lesion treatable to 60 Gy in 10 fractions.
- Repeat radiation in fields previously radiated will be allowed at the discretion of the treating physician.
- Age >/= 18 years
Key exclusion criteria (10 listed)
- Serious autoimmune disease at the discretion of the treating attending: Patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this study.
- Active diverticulitis, intra-abdominal abscess, Gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of Adverse Events: (AE's) e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Known active HIV, Hepatitis B, or Hepatitis C that has not been documented to be cured.
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 |
|---|---|---|
| IpilimumabAlso: Yervoy, BMS-734016, MDX010Treatment Group 1 and 3: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. Treatment Group 2 and 4: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Treatment Group 5: Ipilimumab 3 mg/kg by vein on Day 1 of Cycle 1. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 2-4 | Drug | Group 1 Liver: Concurrent (early) Ipilimumab and SBRT, Group 2 Liver: Sequential (late) Ipilimumab and SBRT, Group 3 Lung: Concurrent (early) Ipilimumab and SBRT, Group 4 Lung: Sequential (late) Ipilimumab and SBRT, Group 5 Liver/Lung Metastasis: (late) Ipilimumab and SBRT, Thyroid Expansion Cohort |
| Stereotactic Body Radiation Therapy (SBRT)Also: SBRT, XRTTreatment Group 1 and 3: SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 1 - 4 of Cycle 1. Treatment Group 2 and 4: SBRT 50 Gy in 4 fractions to 1-4 liver lesion(s) on Days 29 - 33 of each 21 day cycle. Treatment Group 5: SBRT 60 Gy in 10 fractions to 1 - 4 lung, liver, or adrenal lesion (s) on Days 1 - 5 and Days 9 - 12 of Cycle 1. | Radiation | Group 1 Liver: Concurrent (early) Ipilimumab and SBRT, Group 2 Liver: Sequential (late) Ipilimumab and SBRT, Group 3 Lung: Concurrent (early) Ipilimumab and SBRT, Group 4 Lung: Sequential (late) Ipilimumab and SBRT, Group 5 Liver/Lung Metastasis: (late) Ipilimumab and SBRT, Thyroid Expansion Cohort |
Primary outcome
Maximum Tolerated Dose (MTD) of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT)
Time frame: Third week of second, 21 day cycle
MTD defined as highest dose level with less than 2 patients with dose limiting toxicity (DLT) out of at least six patients in the cohort. All enrolled participants will be considered in the DLT analysis. If at any time more than or equal to one third (33%) of participants at a dose level experience DLT, the MTD will be reassessed and the next lowest dose level for the combination therapy considered the MTD.
1 secondary outcome
Response Rate of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT)
Time frame: 30 days after last dose of Ipilimumab
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2020.
- Derived from this study: PubMed 36921766He K, Hong DS, Tang C, Sezen D, Cox L, Maleki A, Bertolet G, Nguyen QN, Comeaux NI, Schuda L, Chen D, Welsh JW. Five-year overall survival with ipilimumab and stereotactic ablative radiotherapy for metastatic disease. Radiother Oncol. 2023 Jun;183:109618. doi: 10.1016/j.radonc.2023.109618. Epub 2023 Mar 13.
- Derived from this study: PubMed 31996395Chen D, Menon H, Verma V, Guo C, Ramapriyan R, Barsoumian H, Younes A, Hu Y, Wasley M, Cortez MA, Welsh J. Response and outcomes after anti-CTLA4 versus anti-PD1 combined with stereotactic body radiation therapy for metastatic non-small cell lung cancer: retrospective analysis of two single-institution prospective trials. J Immunother Cancer. 2020 Jan;8(1):e000492. doi: 10.1136/jitc-2019-000492.
- Derived from this study: PubMed 27240885Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016 Dec 3;388(10061):2783-2795. doi: 10.1016/S0140-6736(16)30172-6. Epub 2016 May 27.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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. This study is not recruiting at the moment.
James Welsh, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) in people with Liver Cancer and Lung Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
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 10 inclusion and 10 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: finished, as of the sponsor's last update on 30 Nov 2020. 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 United States. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) (time frame: Third week of second, 21 day cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02239900, which also lists 3 linked publications.
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 30 Nov 2020.