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Neoadjuvant and Adjuvant Checkpoint Blockade in Patients With Clinical Stage III or Oligometastatic Stage IV Melanoma

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ClinicalTrials.gov Identifier: NCT02519322
Recruitment Status : Active, not recruiting
First Posted : August 10, 2015
Last Update Posted : July 9, 2018
Sponsor:
Collaborators:
Bristol-Myers Squibb
United States Department of Defense
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

You are being asked to take part in this study because you have melanoma that is metastatic (has spread) and you are going to have surgery to remove the disease.

The goal of this clinical research study is to learn if giving nivolumab alone or in combination with ipilimumab before and after surgery can help to control metastatic melanoma. The safety of these drugs will also be studied.

This is an investigational study. Ipilimumab and nivolumab are FDA approved and commercially available to treat metastatic melanoma. It is investigational to give the drugs in combination before and after surgery. The study doctor can explain how the study drugs are designed to work.

Up to 38 participants will be enrolled in this study. Up to 32 will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Melanoma Oligometastatic Melanoma Drug: Nivolumab 1mg/kg Drug: Ipilimumab Drug: Nivolumab 3 mg/kg Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant and Adjuvant Checkpoint Blockade in Patients With Clinical Stage III or Oligometastatic Stage IV Melanoma
Actual Study Start Date : February 2, 2016
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Group A - Nivolumab

Neoadjuvant phase: Nivolumab 3 mg/kg by vein every 2 weeks on weeks 1, 3, 5 and 7 prior to surgical excision.

Adjuvant Phase: Nivolumab 3 mg/kg by vein every 2 weeks postoperatively for 6 months.

Drug: Nivolumab 3 mg/kg

Group A Neoadjuvant Phase: Nivolumab 3 mg/kg by vein every 2 weeks on weeks 1, 3, 5 and 7 prior to surgical excision.

Group A Adjuvant Phase: Nivolumab 3 mg/kg by vein every 2 weeks postoperatively for 6 months.

Group B Adjuvant Phase: Nivolumab 3 mg/kg by vein every 2 weeks postoperatively for 6 months.

Other Names:
  • BMS-936558
  • Opdivo

Experimental: Group B - Nivolumab + Ipilimumab

Neoadjuvant Phase: Nivolumab 1 mg/kg by vein combined with Ipilimumab 3 mg/kg by vein every 3 weeks on weeks 1, 4 and 7 prior to surgical excision.

Adjuvant Phase: Nivolumab 3 mg/kg by vein every 2 weeks postoperatively for 6 months.

Drug: Nivolumab 1mg/kg
Group B Neoadjuvant Phase: Nivolumab 1 mg/kg by vein every 3 weeks on weeks 1, 4 and 7 prior to surgical excision.
Other Names:
  • BMS-936558
  • Opdivo

Drug: Ipilimumab
Group B Neoadjuvant Phase: Ipilimumab 3 mg/kg by vein every 3 weeks on weeks 1, 4 and 7 prior to surgical excision.
Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

Drug: Nivolumab 3 mg/kg

Group A Neoadjuvant Phase: Nivolumab 3 mg/kg by vein every 2 weeks on weeks 1, 3, 5 and 7 prior to surgical excision.

Group A Adjuvant Phase: Nivolumab 3 mg/kg by vein every 2 weeks postoperatively for 6 months.

Group B Adjuvant Phase: Nivolumab 3 mg/kg by vein every 2 weeks postoperatively for 6 months.

Other Names:
  • BMS-936558
  • Opdivo




Primary Outcome Measures :
  1. Pathologic Response of Neoadjuvant Nivolumab in Participants with High-Risk Resectable Melanoma [ Time Frame: Day 57 ]
    Pathologic complete response (pCR) defined as the absence of any residual invasive malignant cells on hematoxylin and eosin evaluation of the resected melanoma specimen.

  2. Pathologic Response of Neoadjuvant Nivolumab and Ipilimumab in Participants with High-Risk Resectable Melanoma [ Time Frame: Day 57 ]
    Pathologic complete response (pCR) defined as the absence of any residual invasive malignant cells on hematoxylin and eosin evaluation of the resected melanoma specimen. Pathologic partial response (pPR) defined as less than 50% viable tumor cells or more than 50% fibrosis on pathological evaluation.


Secondary Outcome Measures :
  1. Immunologic Response of Neoadjuvant Nivolumab in Participants with High-Risk Resectable Melanoma [ Time Frame: Baseline, Day 57, and 2 weeks after surgery ]
    Immunologic response determined by change in T cell infiltrate from baseline to on-treatment and surgical specimens in response to therapy.

  2. Immunologic Response of Neoadjuvant Nivolumab and Ipilimumab Participants with High-Risk Resectable Melanoma [ Time Frame: Baseline, Day 57, and 2 weeks after surgery ]
    Immunologic response determined by change in T cell infiltrate from baseline to on-treatment and surgical specimens in response to therapy.



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. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
  2. Patients must have histologically or cytologically confirmed Stage IIIB/C or Stage IV oligometastatic melanoma. Oligometastatic melanoma is defined as three or fewer areas of resectable disease excluding central nervous system and bone involvement. Patients with cutaneous, mucosal, acral, ocular or unknown primary melanomas are eligible for enrollment. For patients with stage IV disease with distant lymph nodes (stage M1a), a maximum of three separate lymph node sites fit the definition of oligometastatic disease. Resectable tumors are defined as having no significant vascular, neural or bony involvement. Only cases where a complete surgical resection with tumor-free margins can safely be achieved are defined as resectable.
  3. Patients will have at least one melanoma deposit that can undergo serial biopsy (at least 2 time points) during the neoadjuvant phase of the protocol. Patients must be willing to provide tumor samples at the time points specified in the Study Procedure Tables.
  4. All patients must undergo a baseline tumor biopsy for PD-L1 testing (PD-L1 positivity is determined by greater than or equal to 1% of cells staining in the membrane by immunohistochemistry). The 28-8 clone for PD-L1 testing is required for assessment of PD-L1 status. For patients with stage IV disease, site of tumor biopsy will preferably be from non-lymph node disease site. For PD-L1 testing, the biopsy should contain sufficient tumor content (>/=100 tumor cells/4-micron tissue section). If a sample contains insufficient tumor content, a re-biopsy will be required to obtain a sample with sufficient tumor content prior to treatment.
  5. Patients must be medically fit enough to undergo surgery as determined by the treating medical and surgical oncology team
  6. Patients who have been previously treated in the adjuvant setting for melanoma will be eligible for treatment after a 28 day wash-out period
  7. Patients must have measurable disease, defined by RECIST 1.1
  8. Age >/= 18 years
  9. ECOG performance status 0-1
  10. Patients must have organ and marrow function as defined below: Hematologic Absolute neutrophil count (ANC) >/= 1.5 X 10^9/L; Hemoglobin >/= 9.5 g/dL Platelets >/= 100 X 10^9/L PT/INR and PTT </= 1.5 X ULN. Hepatic Total bilirubin </= 1.5 X ULN (isolated bilirubin >1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) AST and ALT Albumin </= 2.5 X ULN 1 >/=2.5 g/dL Renal Creatinine OR Calculated creatinine clearance OR 24-hour urine creatinine clearance </=1.5 X ULN 2 >/= 50 mL/min >/= 50 mL/min
  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.
  12. 11b) 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. The half-life of nivolumab and ipilimumab is up to 25 days and 18 days, respectively. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug. 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.
  13. Women must not be breastfeeding
  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 31 weeks (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.

Exclusion Criteria:

  1. Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug
  2. Any major surgery within the last 3 weeks
  3. Brain metastases, leptomeningeal disease or bone metastases
  4. Pregnant or lactating female
  5. Unwillingness or inability to follow the procedures required in the protocol
  6. Current use of anticoagulants (warfarin, heparin, direct thrombin inhibitors) at therapeutic levels
  7. 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.
  8. Prior malignancy active within the previous 2 years except for patient's prior diagnosis of melanoma 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).
  9. 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.
  10. 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.
  11. Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody
  12. Any positive test result for hepatitis B or C virus indicating acute or chronic infection
  13. Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome
  14. History of severe hypersensitivity reaction to any monoclonal antibody
  15. Prisoners or subjects who are involuntarily incarcerated
  16. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (infection disease) illness

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): NCT02519322


Locations
United States, New York
Memorial Sloan Kettering
New York, New York, United States, 10065
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
United States Department of Defense
Investigators
Principal Investigator: Rodabe N. Amaria, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02519322     History of Changes
Other Study ID Numbers: 2015-0041
NCI-2015-01520 ( Registry Identifier: NCI CTRP )
First Posted: August 10, 2015    Key Record Dates
Last Update Posted: July 9, 2018
Last Verified: July 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:
Melanoma
Oligometastatic melanoma
Resectable
Nivolumab
BMS-936558
Opdivo
Ipilimumab
Yervoy
BMS-734016
MDX010

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs