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

NCT02239900 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 2013-0882NCI-2015-00042
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Liver Cancer; Lung Cancer

Keywords

Liver Cancer; Lung Cancer; Adrenal Gland; Metastasis; Advanced Solid Malignancies; Ipilimumab; Yervoy; BMS-734016; MDX010; Stereotactic Body Radiation Therapy; SBRT; XRT

Outcome Measures

Primary Outcomes (1)

• 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.

  Third week of second, 21 day cycle

Secondary Outcomes (1)

• Response Rate of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT)

  30 days after last dose of Ipilimumab

Study Arms (6)

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.

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.

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.

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.

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.

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.

Drug: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

Ipilimumab DRUG

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

Also known as: Yervoy, BMS-734016, MDX010

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) RADIATION

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.

Also known as: SBRT, XRT

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

Eligibility Criteria

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

You may qualify if:

• Patients must have histological confirmation of metastatic cancer with at least one metastatic or primary lesion in the liver, lung, or adrenal gland.
• 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%).
• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• 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.

  PMID: 36921766 DERIVED

• Chen 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.

  PMID: 31996395 DERIVED

• Cabanillas 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.

  PMID: 27240885 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Liver Neoplasms; Lung Neoplasms; Neoplasm Metastasis

Interventions

Ipilimumab; Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• James Welsh, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2014
• First Posted: September 15, 2014
• Study Start: August 26, 2014
• Primary Completion: October 25, 2019
• Study Completion: October 25, 2019
• Last Updated: November 30, 2020

Record last verified: 2020-11

Locations

US (1)