Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) in Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT02239900
First received: September 11, 2014
Last updated: December 7, 2016
Last verified: December 2016
  Purpose
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.

Condition Intervention Phase
Liver Cancer
Lung Cancer
Drug: Ipilimumab
Radiation: Stereotactic Body Radiation Therapy (SBRT)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Ipilimumab (Immunotherapy) and Hypofractionated Stereotactic Radiation Therapy in Patients With Advanced Solid Malignancies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Response Rate of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) [ Time Frame: 30 days after last dose of Ipilimumab ]
    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.


Estimated Enrollment: 120
Study Start Date: August 2014
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 Liver: Concurrent (early) Ipilimumab and 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.
Drug: Ipilimumab

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

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
Radiation: Stereotactic Body Radiation Therapy (SBRT)

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.

Other Names:
  • SBRT
  • XRT
Experimental: Group 2 Liver: Sequential (late) Ipilimumab and 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.
Drug: Ipilimumab

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

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
Radiation: Stereotactic Body Radiation Therapy (SBRT)

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.

Other Names:
  • SBRT
  • XRT
Experimental: Group 3 Lung: Concurrent (early) Ipilimumab and 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.
Drug: Ipilimumab

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

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
Radiation: Stereotactic Body Radiation Therapy (SBRT)

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.

Other Names:
  • SBRT
  • XRT
Experimental: Group 4 Lung: Sequential (late) Ipilimumab and 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.
Drug: Ipilimumab

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

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
Radiation: Stereotactic Body Radiation Therapy (SBRT)

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.

Other Names:
  • SBRT
  • XRT
Experimental: Group 5 Liver/Lung Metastasis: (late) Ipilimumab and 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.
Drug: Ipilimumab

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

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
Radiation: Stereotactic Body Radiation Therapy (SBRT)

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.

Other Names:
  • SBRT
  • XRT
Experimental: Thyroid Expansion Cohort

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.

Drug: Ipilimumab

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

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
Radiation: Stereotactic Body Radiation Therapy (SBRT)

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.

Other Names:
  • SBRT
  • XRT

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have histological confirmation of metastatic cancer with at least one metastatic or primary lesion in the liver, lung, or adrenal gland.
  2. 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.
  3. 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.
  4. Repeat radiation in fields previously radiated will be allowed at the discretion of the treating physician.
  5. Age >/= 18 years
  6. ECOG performance status </=2 (Karnofsky >60%).
  7. 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
  8. Patients must be willing and able to review, understand, and provide written consent before starting therapy.
  9. 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
  10. Patients that have previously progressed on immunotherapy such as ipilimumab will be eligible.

Exclusion Criteria:

  1. 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.
  2. Active diverticulitis, intra-abdominal abscess, Gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
  3. 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.
  4. 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.
  5. Known active HIV, Hepatitis B, or Hepatitis C that has not been documented to be cured.
  6. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).
  7. 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).
  8. 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.
  9. History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.
  10. Prior allogeneic stem cell transplantation;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02239900

Contacts
Contact: James Welsh, MD 713-563-2300

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: James Welsh, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02239900     History of Changes
Other Study ID Numbers: 2013-0882
NCI-2015-00042 ( Registry Identifier: NCI CTRP )
Study First Received: September 11, 2014
Last Updated: December 7, 2016

Keywords provided by M.D. Anderson Cancer Center:
Liver Cancer
Lung Cancer
Adrenal Gland
Metastasis
Advanced Solid Malignancies
Ipilimumab
Yervoy
BMS-734016
MDX010
Stereotactic Body Radiation Therapy
SBRT
XRT

Additional relevant MeSH terms:
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Liver Extracts
Antibodies, Monoclonal
Hematinics
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 27, 2017