Melanoma Clinical Trial
Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by Surgery
Summary
This pilot phase II trial studies how well pembrolizumab works in treating patients with desmoplastic melanoma (DM) that can be removed by surgery (resectable) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Full Description
PRIMARY OBJECTIVES:
I. To evaluate the pathologic complete response rate (pCR) in patients with resectable desmoplastic melanoma treated with neoadjuvant pembrolizumab (MK-3475). (Cohort A) II. To evaluate the complete response rate (confirmed and unconfirmed) in patients with unresectable desmoplastic melanoma treated with pembrolizumab (MK-3475). (Cohort B)
SECONDARY OBJECTIVES:
I. To estimate the 9 week response rate (RR) (unconfirmed complete and partial responses) among patients with measurable disease. (Cohort A) II. To estimate the median overall survival (OS). (Cohort A) III. To evaluate safety and tolerability of pembrolizumab (MK-3475) in the neoadjuvant setting. (Cohort A) IV. To estimate the median progression-free survival (PFS). (Cohort B) V. To estimate the median overall survival (OS). (Cohort B) VI. To evaluate safety and tolerability of pembrolizumab (MK-3475) in this setting. (Cohort B)
OTHER OBJECTIVES:
I. To evaluate the hypothesis that higher mutational load in the patient derived baseline tumor biopsy samples is associated with higher pathologic complete response (pCR).
II. To evaluate T cell infiltration into the tumors and circulating tumor deoxyribonucleic acid (DNA) profile from blood samples in DM patients and correlate with response to programmed cell death protein 1 (PD-1) blockade.
III. To evaluate the clonality of tumor infiltrating T cells in DM patients and correlate with response to PD-1 blockade.
IV. To evaluate adaptive immune resistant mechanism in DM tumors.
OUTLINE: Patients are enrolled to 1 of 2 cohorts.
COHORT A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.
COHORT B: Patients with unresectable disease receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.
Patients undergo computed tomography (CT) scan and may undergo position emission tomography (PET) and magnetic resonance imaging (MRI) throughout the study. Patients also undergo blood sample collection at screening and tumor biopsy throughout the study.
After completion of study treatment, patients are followed up at 6 weeks after the last dose, then every 12 weeks to the end of the first year, then every 6 months to the end of the fifth year after registration. After progression, patients are followed every 6 months for up to 2 years from the date of registration, then annually thereafter until 5 years from registration.
Eligibility Criteria
Inclusion Criteria:
COHORT A: Patients must have histologically or cytologically confirmed primary desmoplastic melanoma that is deemed resectable; the decision to perform surgery on patients must be based on good clinical judgment; eligible patients for surgical resection must have disease that, in the judgment of the surgeon, is deemed completely resectable resulting in free surgical margins; patients must have residual disease after initial biopsy which can be measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; residual disease can either be confirmed with fine-needle aspiration (FNA) or if measurable disease is present, no FNA needs to be obtained OR
COHORT B: Patients must have histologically or cytologically confirmed primary desmoplastic melanoma that is unresectable; patients in Cohort B must have measurable disease per RECIST 1.1
Contrast-enhanced computed tomography (CT) scans of the chest, abdomen and pelvis are required; a whole body positron emission tomography (PET)/CT scan with diagnostic quality images and intravenous iodinated contrast may be used in lieu of a contrast enhanced CT of the chest, abdomen and pelvis; imaging of the head and neck is required only if the patient has a head/neck primary; contrast may be omitted if the treating investigator believes that exposure to contrast poses an excessive risk to the patient; if skin lesions are being followed as measurable disease, photograph with a ruler included and physician measurements, must be kept in the patient's chart as source documentation; all measurable lesions must be assessed within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration; all disease must be assessed and documented on the baseline tumor assessment form (RECIST 1.1)
Patients must not have known brain metastases unless brain metastases have been treated and patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 14 days prior to registration
Patients must not have received prior systemic treatment for this melanoma
Patients must not be planning to receive concomitant other biologic therapy, hormonal therapy, other chemotherapy, anti-cancer surgery or other anti-cancer therapy while on this protocol
Patients must not have received radiation therapy, non-cytotoxic agents or investigational agents or systemic corticosteroids within 14 days prior to registration
Patients may have received prior surgery; all adverse events associated with prior surgery must have resolved to =< grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] 4.0) prior to registration
Patients must be >= 18 years of age
Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to registration)
Platelets >= 50,000/mcl (obtained within 28 days prior to registration)
Hemoglobin >= 8 g/dL (obtained within 28 days prior to registration)
Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (or =< 3.0 x IULN with Gilbert's syndrome) (obtained within 28 days prior to registration)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN (or < 5 x IULN for patients with known liver metastases) (obtained within 28 days prior to registration)
Patients must have lactate dehydrogenase (LDH) performed within 28 days prior to registration
Patients must have Zubrod performance status =< 2
Patients must not have history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Patients must not have an active infection requiring systemic therapy
Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Patients must not have received live vaccines within 42 days prior to registration; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
Patients known to be human immunodeficiency virus (HIV) positive prior to registration are eligible if they meet the following criteria within 30 days prior to registration: stable and adequate CD4 counts (>= 350 mm^3), and serum HIV viral load of < 25,000 IU/ml; patients must be on a stable anti-viral therapy
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated in situ cancer, adequately treated stage I or II cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years
Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to registration; women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures; patients must not be pregnant or nursing due to unknown teratogenic side effects
Patients must have specimens available and institutions must be planning to submit for centralized pathology review and for integrated translational medicine objectives
Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
As a part of the Oncology Patient Enrollment Network (OPEN) registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 247 Locations for this study
Fairbanks Alaska, 99701, United States
Phoenix Arizona, 85004, United States
Fort Smith Arkansas, 72903, United States
Hot Springs Arkansas, 71913, United States
Arroyo Grande California, 93420, United States
Duarte California, 91010, United States
Dublin California, 94568, United States
Emeryville California, 94608, United States
Emeryville California, 94608, United States
Los Angeles California, 90033, United States
Los Angeles California, 90033, United States
Los Angeles California, 90095, United States
Martinez California, 94553, United States
Newport Beach California, 92663, United States
Oakland California, 94609, United States
Oakland California, 94609, United States
Pasadena California, 91105, United States
San Luis Obispo California, 93401, United States
Santa Maria California, 93444, United States
South Pasadena California, 91030, United States
Upland California, 91786, United States
Walnut Creek California, 94597, United States
Aurora Colorado, 80012, United States
Aurora Colorado, 80012, United States
Boulder Colorado, 80301, United States
Boulder Colorado, 80303, United States
Boulder Colorado, 80304, United States
Centennial Colorado, 80112, United States
Colorado Springs Colorado, 80907, United States
Colorado Springs Colorado, 80907, United States
Denver Colorado, 80204, United States
Denver Colorado, 80206, United States
Denver Colorado, 80209, United States
Denver Colorado, 80210, United States
Denver Colorado, 80218, United States
Denver Colorado, 80218, United States
Denver Colorado, 80218, United States
Denver Colorado, 80218, United States
Denver Colorado, 80220, United States
Denver Colorado, 80220, United States
Denver Colorado, 80220, United States
Durango Colorado, 81301, United States
Durango Colorado, 81301, United States
Englewood Colorado, 80113, United States
Englewood Colorado, 80113, United States
Golden Colorado, 80401, United States
Grand Junction Colorado, 81501, United States
Grand Junction Colorado, 81505, United States
Greeley Colorado, 80631, United States
Lafayette Colorado, 80026, United States
Lakewood Colorado, 80228, United States
Littleton Colorado, 80120, United States
Littleton Colorado, 80122, United States
Lone Tree Colorado, 80124, United States
Lone Tree Colorado, 80124, United States
Longmont Colorado, 80501, United States
Longmont Colorado, 80501, United States
Loveland Colorado, 80539, United States
Parker Colorado, 80138, United States
Pueblo Colorado, 81004, United States
Thornton Colorado, 80260, United States
Wheat Ridge Colorado, 80033, United States
Hartford Connecticut, 06102, United States
Aventura Florida, 33180, United States
Fort Lauderdale Florida, 33308, United States
Miami Beach Florida, 33140, United States
Tampa Florida, 33607, United States
Tampa Florida, 33612, United States
Tampa Florida, 33612, United States
Savannah Georgia, 31404, United States
Savannah Georgia, 31405, United States
Savannah Georgia, 31405, United States
Boise Idaho, 83706, United States
Caldwell Idaho, 83605, United States
Coeur d'Alene Idaho, 83814, United States
Emmett Idaho, 83617, United States
Meridian Idaho, 83642, United States
Nampa Idaho, 83687, United States
Post Falls Idaho, 83854, United States
Sandpoint Idaho, 83864, United States
Alton Illinois, 62002, United States
Aurora Illinois, 60504, United States
Chicago Illinois, 60611, United States
Danville Illinois, 61832, United States
Effingham Illinois, 62401, United States
Geneva Illinois, 60134, United States
Lake Forest Illinois, 60045, United States
Mattoon Illinois, 61938, United States
Mount Vernon Illinois, 62864, United States
Urbana Illinois, 61801, United States
Urbana Illinois, 61801, United States
Warrenville Illinois, 60555, United States
Yorkville Illinois, 60560, United States
Evansville Indiana, 47713, United States
Newburgh Indiana, 47630, United States
Clive Iowa, 50325, United States
Clive Iowa, 50325, United States
Council Bluffs Iowa, 51503, United States
Creston Iowa, 50801, United States
Des Moines Iowa, 50314, United States
Des Moines Iowa, 50314, United States
West Des Moines Iowa, 50266, United States
Coffeyville Kansas, 67337, United States
Fairway Kansas, 66205, United States
Garden City Kansas, 67846, United States
Great Bend Kansas, 67530, United States
Hays Kansas, 67601, United States
Kansas City Kansas, 66112, United States
Kansas City Kansas, 66160, United States
Lawrence Kansas, 66044, United States
Lenexa Kansas, 66219, United States
Lenexa Kansas, 66219, United States
Olathe Kansas, 66061, United States
Overland Park Kansas, 66209, United States
Overland Park Kansas, 66210, United States
Pittsburg Kansas, 66762, United States
Salina Kansas, 67401, United States
Topeka Kansas, 66606, United States
Westwood Kansas, 66205, United States
Bardstown Kentucky, 40004, United States
Corbin Kentucky, 40701, United States
Lexington Kentucky, 40504, United States
Lexington Kentucky, 40509, United States
London Kentucky, 40741, United States
Louisville Kentucky, 40202, United States
Louisville Kentucky, 40215, United States
Louisville Kentucky, 40245, United States
Shepherdsville Kentucky, 40165, United States
Brownstown Michigan, 48183, United States
Clinton Township Michigan, 48038, United States
Dearborn Michigan, 48126, United States
Detroit Michigan, 48202, United States
Jackson Michigan, 49201, United States
Monroe Michigan, 48162, United States
Novi Michigan, 48377, United States
Shelby Michigan, 48315, United States
West Bloomfield Michigan, 48322, United States
Burnsville Minnesota, 55337, United States
Burnsville Minnesota, 55337, United States
Cambridge Minnesota, 55008, United States
Coon Rapids Minnesota, 55433, United States
Edina Minnesota, 55435, United States
Fridley Minnesota, 55432, United States
Maple Grove Minnesota, 55369, United States
Maplewood Minnesota, 55109, United States
Maplewood Minnesota, 55109, United States
Minneapolis Minnesota, 55407, United States
Minneapolis Minnesota, 55415, United States
Minneapolis Minnesota, 55454, United States
Monticello Minnesota, 55362, United States
New Ulm Minnesota, 56073, United States
Princeton Minnesota, 55371, United States
Robbinsdale Minnesota, 55422, United States
Saint Louis Park Minnesota, 55416, United States
Saint Paul Minnesota, 55101, United States
Saint Paul Minnesota, 55102, United States
Shakopee Minnesota, 55379, United States
Stillwater Minnesota, 55082, United States
Waconia Minnesota, 55387, United States
Willmar Minnesota, 56201, United States
Woodbury Minnesota, 55125, United States
Wyoming Minnesota, 55092, United States
Pascagoula Mississippi, 39581, United States
Ballwin Missouri, 63011, United States
Bolivar Missouri, 65613, United States
Branson Missouri, 65616, United States
Independence Missouri, 64057, United States
Joplin Missouri, 64804, United States
Joplin Missouri, 64804, United States
Kansas City Missouri, 64108, United States
Kansas City Missouri, 64131, United States
Kansas City Missouri, 64132, United States
Kansas City Missouri, 64154, United States
Lee's Summit Missouri, 64064, United States
Rolla Missouri, 65401, United States
Rolla Missouri, 65401, United States
Saint Joseph Missouri, 64506, United States
Saint Louis Missouri, 63109, United States
Saint Louis Missouri, 63128, United States
Saint Louis Missouri, 63141, United States
Springfield Missouri, 65804, United States
Springfield Missouri, 65807, United States
Washington Missouri, 63090, United States
Anaconda Montana, 59711, United States
Billings Montana, 59101, United States
Billings Montana, 59101, United States
Billings Montana, 59102, United States
Bozeman Montana, 59715, United States
Butte Montana, 59701, United States
Great Falls Montana, 59405, United States
Great Falls Montana, 59405, United States
Helena Montana, 59601, United States
Kalispell Montana, 59901, United States
Missoula Montana, 59804, United States
Grand Island Nebraska, 68803, United States
Kearney Nebraska, 68847, United States
Lincoln Nebraska, 68510, United States
Omaha Nebraska, 68122, United States
Omaha Nebraska, 68124, United States
Omaha Nebraska, 68130, United States
Omaha Nebraska, 68131, United States
Papillion Nebraska, 68046, United States
Buffalo New York, 14263, United States
Clinton North Carolina, 28328, United States
Goldsboro North Carolina, 27534, United States
Goldsboro North Carolina, 27534, United States
Jacksonville North Carolina, 28546, United States
Jacksonville North Carolina, 28546, United States
Belpre Ohio, 45714, United States
Chillicothe Ohio, 45601, United States
Cincinnati Ohio, 45220, United States
Cincinnati Ohio, 45242, United States
Cincinnati Ohio, 45247, United States
Cincinnati Ohio, 45255, United States
Columbus Ohio, 43210, United States
Columbus Ohio, 43213, United States
Columbus Ohio, 43214, United States
Columbus Ohio, 43214, United States
Columbus Ohio, 43215, United States
Columbus Ohio, 43219, United States
Columbus Ohio, 43222, United States
Columbus Ohio, 43228, United States
Delaware Ohio, 43015, United States
Delaware Ohio, 43015, United States
Delaware Ohio, 43015, United States
Dublin Ohio, 43016, United States
Grove City Ohio, 43123, United States
Lancaster Ohio, 43130, United States
Lima Ohio, 45801, United States
Mansfield Ohio, 44903, United States
Marietta Ohio, 45750, United States
Marion Ohio, 43302, United States
Mount Vernon Ohio, 43050, United States
Newark Ohio, 43055, United States
Newark Ohio, 43055, United States
Perrysburg Ohio, 43551, United States
Portsmouth Ohio, 45662, United States
Sylvania Ohio, 43560, United States
Toledo Ohio, 43606, United States
Toledo Ohio, 43608, United States
Toledo Ohio, 43623, United States
Westerville Ohio, 43081, United States
Zanesville Ohio, 43701, United States
Oklahoma City Oklahoma, 73104, United States
Oklahoma City Oklahoma, 73120, United States
Baker City Oregon, 97814, United States
Ontario Oregon, 97914, United States
Bryan Texas, 77802, United States
American Fork Utah, 84003, United States
Cedar City Utah, 84720, United States
Farmington Utah, 84025, United States
Logan Utah, 84321, United States
Murray Utah, 84107, United States
Ogden Utah, 84403, United States
Provo Utah, 84604, United States
Riverton Utah, 84065, United States
Saint George Utah, 84770, United States
Salt Lake City Utah, 84106, United States
Salt Lake City Utah, 84112, United States
Salt Lake City Utah, 84143, United States
South Jordan Utah, 84009, United States
Auburn Washington, 98001, United States
Bremerton Washington, 98310, United States
Burien Washington, 98166, United States
Enumclaw Washington, 98022, United States
Federal Way Washington, 98003, United States
Gig Harbor Washington, 98335, United States
Lakewood Washington, 98499, United States
Port Townsend Washington, 98368, United States
Poulsbo Washington, 98370, United States
Puyallup Washington, 98372, United States
Silverdale Washington, 98383, United States
Spokane Valley Washington, 99216, United States
Spokane Washington, 99204, United States
Spokane Washington, 99218, United States
Tacoma Washington, 98405, United States
Tacoma Washington, 98405, United States
Tacoma Washington, 98405, United States
Tacoma Washington, 98405, United States
New Richmond Wisconsin, 54017, United States
Cheyenne Wyoming, 82001, United States
Cody Wyoming, 82414, United States
Sheridan Wyoming, 82801, United States
How clear is this clinincal trial information?