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Trial record 18 of 65 for:    Sarcoma | "Dermatofibroma"

Study of Neoadjuvant Checkpoint Blockade in Patients With Surgically Resectable Undifferentiated Pleomorphic Sarcoma and Dedifferentiated Liposarcoma

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ClinicalTrials.gov Identifier: NCT03307616
Recruitment Status : Recruiting
First Posted : October 12, 2017
Last Update Posted : October 12, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if giving nivolumab alone or in combination with ipilimumab before standard-of-care surgery can help to control sarcoma. As part of your standard-of-care, you may also receive radiation therapy. The safety of this combination will also be studied.

This is an investigational study. Ipilimumab and nivolumab are FDA approved and commercially available to treat melanoma, lung cancer, and renal cell cancer. It is considered investigational to use these drugs to treat sarcoma. The study doctor can explain how the study drugs are designed to work.

Up to 40 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Systemic Connective Tissue Disorders Drug: Nivolumab Drug: Ipilimumab Radiation: Radiation Therapy Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Neoadjuvant Checkpoint Blockade in Patients With Surgically Resectable Undifferentiated Pleomorphic Sarcoma and Dedifferentiated Liposarcoma
Actual Study Start Date : October 4, 2017
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021


Arm Intervention/treatment
Experimental: Arm A - Nivolumab

Arm consists of treatment naive primary or locally recurrent dedifferentiated liposarcoma (DDLPS) of the retroperitoneum participants.

Participants receive Nivolumab by vein over about 1 hour on Days 1, 15, and 29.

Drug: Nivolumab

Arm A: Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 1, 3, and 5.

Arm B: Nivolumab 1 mg/kg by vein on week 1 followed by Nivolumab 3 mg/kg by vein every 2 weeks (+/- 3 days) on weeks 3 and 5.

Arm C: Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 1, 3, 5 and 7.

Arm D: Nivolumab 1 mg/kg by vein on week 1 followed by Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 3, 5 and 7.

Other Names:
  • BMS-936558
  • Opdivo

Experimental: Arm B - Nivolumab + Ipilimumab

Arm consists of treatment naive primary or locally recurrent dedifferentiated liposarcoma (DDLPS) of the retroperitoneum participants.

Participants receive Nivolumab by vein over about 1 hour and Ipilimumab by vein over about 90 minutes on Day 1. Then, participants receive Nivolumab by vein over about 1 hour on Days 15 and 29.

Drug: Nivolumab

Arm A: Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 1, 3, and 5.

Arm B: Nivolumab 1 mg/kg by vein on week 1 followed by Nivolumab 3 mg/kg by vein every 2 weeks (+/- 3 days) on weeks 3 and 5.

Arm C: Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 1, 3, 5 and 7.

Arm D: Nivolumab 1 mg/kg by vein on week 1 followed by Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 3, 5 and 7.

Other Names:
  • BMS-936558
  • Opdivo

Drug: Ipilimumab
Arm B and D: Ipilimumab 3 mg/kg by vein on week 1.
Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

Experimental: Arm C - Nivolumab + Radiation Therapy

Arm consists of undifferentiated pleomorphic sarcoma (UPS) of the trunk or extremities.

Participants receive Nivolumab by vein over about 1 hour on Days 1, 15, 29, and 43. Participants have radiation therapy 1 time each day, 5 days a week (Monday through Friday) from Day 15 to Day 47.

Drug: Nivolumab

Arm A: Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 1, 3, and 5.

Arm B: Nivolumab 1 mg/kg by vein on week 1 followed by Nivolumab 3 mg/kg by vein every 2 weeks (+/- 3 days) on weeks 3 and 5.

Arm C: Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 1, 3, 5 and 7.

Arm D: Nivolumab 1 mg/kg by vein on week 1 followed by Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 3, 5 and 7.

Other Names:
  • BMS-936558
  • Opdivo

Radiation: Radiation Therapy
Arm C and D: Participants have radiation therapy 1 time each day, 5 days a week (Monday through Friday) from Day 15 to Day 47.
Other Name: XRT

Experimental: Arm D - Nivolumab + Ipilimumab + Radiation Therapy

Arm consists of undifferentiated pleomorphic sarcoma (UPS) of the trunk or extremities.

Participants receive Nivolumab by vein over about 1 hour and Ipilimumab by vein over about 90 minutes on Day 1. Then, participants receive Nivolumab by vein over about 1 hour on Days 15, 29, and 43. Participants have radiation therapy 1 time each day, 5 days a week (Monday through Friday) from Day 15 to Day 47.

Drug: Nivolumab

Arm A: Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 1, 3, and 5.

Arm B: Nivolumab 1 mg/kg by vein on week 1 followed by Nivolumab 3 mg/kg by vein every 2 weeks (+/- 3 days) on weeks 3 and 5.

Arm C: Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 1, 3, 5 and 7.

Arm D: Nivolumab 1 mg/kg by vein on week 1 followed by Nivolumab 3 mg/kg by vein every 2 weeks (+/-3 days) on weeks 3, 5 and 7.

Other Names:
  • BMS-936558
  • Opdivo

Drug: Ipilimumab
Arm B and D: Ipilimumab 3 mg/kg by vein on week 1.
Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

Radiation: Radiation Therapy
Arm C and D: Participants have radiation therapy 1 time each day, 5 days a week (Monday through Friday) from Day 15 to Day 47.
Other Name: XRT




Primary Outcome Measures :
  1. Pathologic Response [ Time Frame: After Day 43 for Arms A and B, and After Day 71 for Days C and D ]
    Pathologic Response assessed at time of surgical resection by percentage hyalinization.


Secondary Outcome Measures :
  1. Immunologic Response [ Time Frame: Baseline and each study procedure visit up to 2 years ]
    Immunologic response assessed by change in T cell infiltrate from baseline to each study procedure visit. The change in T cell infiltrate assessed over time for each treatment arm using a generalized linear mixed model with treatment arm indicator, terms for visit, stage of disease, and PD-L1 tumor status.

  2. Change in Immune Infiltrate in Response to Neoadjuvant Nivolumab Monotherapy and Neoadjuvant Nivolumab and Ipilimumab Combination Therapy [ Time Frame: Baseline, at surgery, and during follow up to 2 years ]
    Change in immune infiltrate assessed by analyzing changes in the immune infiltrate in biopsy specimens obtained at baseline and on-treatment, and surgical specimens in response to therapy.

  3. Objective Response Rate (ORR) of Nivolumab Monotherapy and Nivolumab and Ipilimumab Combination Therapy [ Time Frame: Baseline, Day 43 for Arms A and B, on Day 71 for Arms C and D, 6 weeks after surgery, and at 12 weeks after surgery ]
    ORR assessed by imaging (RECIST 1.1 and irRC) in patients with resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

  4. Recurrence-Free Survival (RFS) [ Time Frame: 12 and 24 months ]
    Recurrence-free survival (RFS) defined from time of surgical resection to the date of documented disease recurrence or death from any cause, whichever occurs first. RFS estimated using the Kaplan-Meier method.

  5. Overall Survival (OS) [ Time Frame: 12 and 24 months ]
    Overall survival defined as the time from treatment onset to death. OS estimated using the Kaplan-Meier method.

  6. Safety of Nivolumab Monotherapy and Combination Ipilimumab and Nivolumab in the Neoadjuvant Setting and Peri-Operatively [ Time Frame: Baseline up to 2 years after surgery ]
    Safety of nivolumab monotherapy and combination ipilimumab and nivolumab in the neoadjuvant setting and peri-operatively assessed by CTCAE version 4.0 criteria.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Adult subjects (>18 years) with treatment naïve primary or locally recurrent DDLPS of the retroperitoneum or UPS of the trunk or extremity will be eligible for inclusion in this study only if all of the following criteria apply:
  2. Patients must be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  3. Patients must have disease determined to be surgically resectable and candidates for upfront surgery as agreed upon by a multidisciplinary consensus (Surgical Oncology, Medical Oncology, Radiation Oncology) after presentation at sarcoma multidisciplinary conference. Resectable tumors are defined as having no significant vascular, neural or bony involvement. Only cases where a complete surgical resection can safely be achieved are defined as resectable.
  4. Patients will be evaluated by the anesthesia team prior to surgery
  5. Patient must have recent imaging (CT or MRI, as appropriate) within 4 weeks of trial enrollment, demonstrating measurable disease as defined by RECIST 1.1
  6. Patients must have at least one tumor amenable to serial biopsy in clinic or be willing to undergo serial biopsies through image-guided procedures during the neoadjuvant phase of the protocol. Patients must be willing to provide tumor samples at the time points
  7. Patients must be medically fit to undergo surgery as determined by the treating medical and surgical oncology team and have ECOG performance status 0-2
  8. Patients must have life expectancy > 6 months.
  9. Patients must be immunotherapy-naïve. Those who have previously been treated with conventional chemotherapy for a prior history of sarcoma in the adjuvant setting may be included.
  10. Patients must have organ and marrow function as defined below: White blood cell count > 3K/uL, Absolute neutrophil count (ANC) > 1 K/uL, Hemoglobin > 9 g/dL, Platelets > 100 K/mm3, Serum creatinine </= 2 mg/dL OR creatinine clearance > 50 mL/min, Aspartic transaminase (AST) ≤ 1.5 x upper limit of normal (ULN), Alanine transaminase (ALT) </= 1.5 x ULN, Bilirubin ≤ 1.5 x ULN
  11. Women are eligible to participate if: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL and estradiol < 40 pg/mL (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
  12. Childbearing potential and agrees to use method(s) of contraception. For a teratogenic study drug and/or when there is insufficient information to assess teratogenicity (preclinical studies have not been done), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required. The individual methods of contraception and duration should be determined in consultation with the investigator. Women of childbearing potential (WOCBP) must follow instructions for birth control when the half-life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 30 days plus the time required for the investigational drug to undergo five half-lives. WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.
  13. CONTINUATION OF #10: WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
  14. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. The investigator shall review contraception methods and the time period that contraception must be followed. Men who are sexually active with WOCBP must follow instructions for birth control when the half-life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 90 days plus the time required for the investigational drug to undergo five half-lives. The half-life of nivolumab and ipilimumab is up to 25 days and 18 days, respectively. Therefore, men who are sexually active with WOCBP must continue contraception for 7 months (90 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.
  15. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men do not require contraception.
  16. Women must not be breastfeeding
  17. Other terms for undifferentiated pleomorphic sarcoma (UPS) may include, but are not limited to: pleomorphic undifferentiated sarcoma, unclassified spindle cell sarcoma, spindle cell sarcoma not otherwise specified, pleomorphic spindle cell sarcoma, pleomorphic fibroblastic sarcoma, undifferentiated high-grade pleomorphic sarcoma, pleomorphic sarcoma with prominent inflammation, pleomorphic sarcoma with giant cells, malignant fibrous histiocytoma (including storiform-pleomorphic and inflammatory subtypes), fibrosarcoma, and myxofibrosarcoma (at least intermediate grade; located deep to the fascia in muscle)

Exclusion Criteria:

  1. Disease that is considered surgically unresectable, including, but not limited to significant vascular, neural, or bone involvement, and in cases where a complete surgical resection cannot be safely performed.
  2. Prior intraabdominal surgery within 4 weeks of trial enrollment.
  3. Prior chemotherapy or targeted small molecule therapy of the current sarcoma. In patients with locally recurrent disease, previous systemic chemotherapy of the primary tumor is allowed, as long as treatment was completed prior to study enrollment and patient has recovered (i.e., < Grade 1 or at baseline) from any adverse events due to previously administered agents.
  4. Prior radiation therapy for sarcoma in the same area
  5. Active concurrent second malignancy
  6. Prior or concurrent immunotherapy, including treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody; tumor vaccines; interferon, or interleukins.
  7. Prior malignancy active within the previous 2 years except for patient's prior diagnosis of sarcoma and locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast with local control measures (surgery, radiation).
  8. Non-oncology vaccine therapy used for prevention of infectious disease within 4 weeks of trial enrollment
  9. Pregnant or lactating female
  10. Unwillingness or inability to follow the procedures required in the protocol
  11. Current use of anticoagulants (warfarin, heparin, direct thrombin inhibitors) at therapeutic levels
  12. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
  13. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  14. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Brief dosing for contrast allergy prophylaxis is allowed.
  15. Any positive test result for hepatitis B or C virus indicating acute or chronic infection
  16. Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome
  17. History of severe hypersensitivity reaction to any monoclonal antibody
  18. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (infection disease) illness
  19. Prisoners or subjects who are involuntarily incarcerated

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03307616


Contacts
Contact: Christina L. Roland, MD 713-792-6940 clroland@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       clroland@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: Christina L. Roland, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03307616     History of Changes
Other Study ID Numbers: 2017-0143
NCI-2018-01031 ( Registry Identifier: NCI CTRP )
First Posted: October 12, 2017    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Undifferentiated pleomorphic sarcoma
Undifferentiated pleomorphic sarcoma of the trunk or extremities
Systemic connective tissue disorders
Dedifferentiated liposarcoma
Dedifferentiated liposarcoma of the retroperitoneum
DDLPS
UPS
Nivolumab
BMS-936558
Opdivo
Ipilimumab
Yervoy
BMS-734016
MDX010
Radiation therapy
XRT

Additional relevant MeSH terms:
Sarcoma
Histiocytoma, Malignant Fibrous
Histiocytoma
Liposarcoma
Connective Tissue Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Adipose Tissue
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs