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Pembrolizumab in Treating Patients With Rare Tumors That Cannot Be Removed by Surgery or Are Metastatic

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ClinicalTrials.gov Identifier: NCT02721732
Recruitment Status : Recruiting
First Posted : March 29, 2016
Last Update Posted : November 8, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies how well pembrolizumab works in treating patients with rare tumors that cannot be removed by surgery or have spread to other parts of the body. Monoclonal antibodies, such as pembrolizumab, may block specific proteins found on white blood cells which may strengthen the immune system and control tumor growth.

Condition or disease Intervention/treatment Phase
Carcinoma of Unknown Primary Origin Kidney Medullary Carcinoma Malignant Germ Cell Tumor Metastatic Adrenal Gland Pheochromocytoma Metastatic Malignant Solid Neoplasm Metastatic Paraganglioma Metastatic Penile Carcinoma Paraganglioma Skin Squamous Cell Carcinoma Small Cell Carcinoma Stage IV Adrenal Cortex Carcinoma AJCC v7 Stage IV Penile Cancer AJCC v7 Stage IV Renal Cell Cancer AJCC v7 Unresectable Solid Neoplasm Vascular Neoplasm Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Other: Questionnaire Administration Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 275 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study for the Evaluation of Efficacy of Pembrolizumab (MK-3475) in Patients With Rare Tumors
Actual Study Start Date : August 15, 2016
Estimated Primary Completion Date : August 20, 2020
Estimated Study Completion Date : August 20, 2020


Arm Intervention/treatment
Experimental: Treatment (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or toxicity. Patients with clinical response or disease stabilization may continue treatment for up to an additional 12 months.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Non-progression rate defined as the proportion of subjects in the analysis population who have no progression of disease [ Time Frame: At 27 weeks ]
    Assessed by Response Evaluation Criteria in Solid Tumors 1.1 or according to tumor evaluation criteria best suitable and accepted for the tumor type evaluate. Response for the primary analysis will be determined by the investigator assessment, and a confirmation assessment is required.

  2. Incidence of adverse events graded using Common Terminology Criteria for Adverse Events version 4.03. [ Time Frame: Up to 27 weeks ]
    Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received pembrolizumab, including serious adverse events, events of clinical interest and immune-related adverse experiences.


Secondary Outcome Measures :
  1. Response assessed according to Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: Up to 27 weeks ]
  2. Duration of response defined as time from first response to disease progression in subjects who achieve a PR or better by Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: Up to 2 years ]
    Summarized using Kaplan-Meier methodology using 25th, 50th (median), and 75th percentiles with associated 2-sided 95% confidence intervals, as well as percentage of censored observations.

  3. Progression free survival according to Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: Baseline to the first documented disease progression or death due to any cause, assessed up to 27 weeks ]
  4. Overall survival [ Time Frame: Up to 24 months ]
    Summarized using Kaplan-Meier methodology using 25th, 50th (median), and 75th percentiles with associated 2-sided 95% confidence intervals, as well as percentage of censored observations.

  5. Non-progression-rate determined according to immune-related Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 27 weeks ]
  6. Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Up to 24 months ]
    ECOG performance status will be assessed.


Other Outcome Measures:
  1. Patient responses to the select items of the Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events [ Time Frame: Up to week 81 ]
    Will be examined over time using descriptive statistics to capture the patient symptom toxicity.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Be willing and able to provide written informed consent/assent for the trial
  • Have measurable disease based on RECIST 1.1; only cohort 9 and 10 can have evaluable disease (non-measurable lesions); tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions; patients may have bone metastatic disease evaluable according to tumor evaluation criteria best suitable and accepted for the tumor type evaluated
  • Have one of the following advanced (unresectable and/or metastatic) solid tumor indications that has progressed following standard therapies, where standard therapies are available:

    • Squamous cell carcinoma of the skin
    • Small cell malignancies of non-pulmonary origin
    • Adrenocortical carcinoma
    • Medullary renal cell carcinoma
    • Carcinoma of unknown primary
    • Penile carcinoma
    • Vascular sarcoma
    • Germ cell tumor
    • Paraganglioma-pheochromocytoma
    • Other rare tumors (except those tumor types listed in exclusion)
  • Have failed prior treatment within 6 months of consent date
  • Have biopsiable disease; subjects must have at least one lesion amenable to biopsy; tumor lesions used for biopsy should not be lesions used as RECIST target lesions; in cohort 9: paraganglioma-pheochromocytoma or cohort 10, where there is prominent bony disease, biopsies may not be possible due to the nature of the disease
  • Be willing to provide archival tissue; if archival tissue is not available, or a newly obtained core or excisional biopsy of a tumor lesion will be obtained; newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; in cohort 9: paraganglioma-pheochromocytoma or cohort 10, where there is prominent bony disease, biopsies may not be possible due to the nature of the disease
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Absolute neutrophil count (ANC) >= 1,000/mcL (performed within 28 days of treatment initiation)
  • Platelets >= 75,000/mcL (performed within 28 days of treatment initiation)
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 28 days of treatment initiation)
  • Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =< 1.5 X upper limit of normal (ULN) OR >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed within 28 days of treatment initiation)
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 28 days of treatment initiation)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (performed within 28 days of treatment initiation)
  • Albumin > 2.5 mg/dL (performed within 28 days of treatment initiation)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 28 days of treatment initiation)
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 28 days of treatment initiation)
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
  • For subjects in cohort 2 (small cell malignancies of non-pulmonary origin), confirmation of no brain metastases via imaging

Exclusion Criteria:

  • Is currently participating and receiving study therapy or concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment at the time of administration of first dose of trial treatment; continuation of hormone replacement therapy is permitted; stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a gonadotrophin releasing hormone [GnRH] agonist), ovarian, or breast cancer are not exclusionary
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has a known history of active TB (bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, and diseases for which the treatment could reasonably include pembrolizumab and are not part of the excluded tumor type list or not eligible for the phase I trial
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; immunosuppressive corticosteroid doses (> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of pembrolizumab; Note: corticosteroids given within 24 hours of an imaging study for purposes of pre-medication in patients with hypersensitivity to radiologic contrast agents are allowed
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy; Note: seasonal influenza vaccines for injection are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are not allowed
  • Is participating in cohort 10 and has melanoma; non-small cell lung cancer; hepatocellular carcinoma; Merkel cell carcinoma; colon or rectal adenocarcinoma; anal canal squamous cell carcinoma; pancreas adenocarcinoma; esophageal squamous cell carcinoma or adenocarcinoma (including gastroesophageal [GE] junction); biliary tract adenocarcinoma (gallbladder and biliary tree but excluding ampulla of vater cancers); carcinoid tumors; neuroendocrine carcinomas (well or moderately differentiated pancreatic neuroendocrine tumor); estrogen receptor (ER)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer; triple negative breast cancer; ovarian epithelial, fallopian tube or primary peritoneal carcinoma; endometrial carcinoma; cervical squamous cell cancer; vulvar squamous cell carcinoma; small cell lung cancer; mesothelioma (malignant pleural mesothelioma); thyroid cancer (papillary or follicular subtype); salivary gland carcinoma; nasopharyngeal carcinoma; glioblastoma multiforme; leiomyosarcoma; prostate adenocarcinoma; gastric adenocarcinoma; or small bowel malignancy

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): NCT02721732


Contacts
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Contact: Aung Naing 713-563-1930 anaing@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Aung Naing    713-563-1930      
Principal Investigator: Aung Naing         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Aung Naing M.D. Anderson Cancer Center

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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02721732     History of Changes
Other Study ID Numbers: 2015-0948
NCI-2016-00545 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2015-0948 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: March 29, 2016    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: November 2018

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

Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Carcinoma, Squamous Cell
Neoplasms, Germ Cell and Embryonal
Carcinoma, Renal Cell
Pheochromocytoma
Neoplasms, Unknown Primary
Paraganglioma
Carotid Body Tumor
Penile Neoplasms
Carcinoma, Medullary
Carcinoma, Small Cell
Small Cell Lung Carcinoma
Adrenocortical Carcinoma
Vascular Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Nerve Tissue
Neoplasm Metastasis
Neoplastic Processes