Clinical Trials /

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

NCT02721732

Description:

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.

Related Conditions:
  • Adrenal Cortex Carcinoma
  • Adrenal Gland Pheochromocytoma
  • Angiosarcoma
  • Carcinoma of Unknown Primary Origin
  • Germ Cell Tumor
  • Kaposi Sarcoma
  • Lymphangiosarcoma
  • Paraganglioma
  • Penile Carcinoma
  • Pulmonary Artery Leiomyosarcoma
  • Pulmonary Vein Leiomyosarcoma
  • Renal Cell Carcinoma
  • Skin Squamous Cell Carcinoma
  • Small Cell Carcinoma
  • Superior Vena Cava Leiomyosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Treating Patients With Rare Tumors That Cannot Be Removed by Surgery or Are Metastatic
  • Official Title: Phase II Study for the Evaluation of Efficacy of Pembrolizumab (MK-3475) in Patients With Rare Tumors

Clinical Trial IDs

  • ORG STUDY ID: 2015-0948
  • SECONDARY ID: NCI-2016-00545
  • SECONDARY ID: 2015-0948
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02721732

Conditions

  • 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

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To obtain early indication of efficacy by evaluation of non-progression rate (NPR) at 27
      weeks as defined as the percentage of patients who are alive and progression-free at 27 weeks
      as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) or method of tumor
      evaluation criteria best suitable and accepted for the tumor type evaluated in patients with
      advanced tumor types receiving pembrolizumab.

      SECONDARY OBJECTIVES:

      I. To correlate efficacy by evaluation of tumor size to programmed cell death 1 ligand 1
      (PD-L1) status among patients with advanced tumor types receiving pembrolizumab.

      II. To evaluate safety and tolerability of pembrolizumab in patients with advanced tumors.

      III. To evaluate the percentage of patients with objective response (complete response [CR]
      or partial response [PR]), progression free survival (PFS), overall survival (OS), and
      duration of response (DOR) in patients with advanced tumor types receiving pembrolizumab.

      IV. To evaluate the NPR at 27 weeks (9 cycles), objective response (CR or PR), PFS, and DOR
      as assessed by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) in
      patients with advanced tumor types receiving pembrolizumab.

      V. To correlate the NPR at 27 weeks (9 cycles), objective response (CR or PR), PFS, OS, and
      DOR to PD-L1 status among patients with advanced tumor types receiving pembrolizumab.

      TERTIARY OBJECTIVES:

      I. To evaluate the potential role of tumor-associated immune biomarkers for prediction of
      therapy effectiveness in patients with advanced tumor types receiving pembrolizumab.

      II. To correlate the potential role of tumor-associated immune biomarkers for prediction of
      therapy effectiveness to PD-L1 status among patients with advanced tumor types receiving
      pembrolizumab.

      III. To identify imaging characteristics associated with immunological changes in tumor
      following treatment with pembrolizumab.

      IV. To compare tumor mutation burden and serial assessment of mutation status in biopsies
      obtained at baseline and progression in patients with advanced tumor types receiving
      pembrolizumab.

      V. To evaluate patient-reported outcomes (PRO) utilizing the National Cancer Institute (NCI)
      Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
      questionnaires.

      OUTLINE:

      Patients receive pembrolizumab intravenously (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.

      After completion of study treatment, patients are followed up at 30 days and then every 9-12
      weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients 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.
  • Pembrolizumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Non-progression rate defined as the proportion of subjects in the analysis population who have no progression of disease
Time Frame:At 27 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Response assessed according to Response Evaluation Criteria in Solid Tumors 1.1
Time Frame:Up to 27 weeks
Safety Issue:
Description:
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Up to 24 months
Safety Issue:
Description: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.
Measure:Non-progression-rate determined according to immune-related Response Evaluation Criteria in Solid Tumors
Time Frame:Up to 27 weeks
Safety Issue:
Description:
Measure:Eastern Cooperative Oncology Group (ECOG) performance status
Time Frame:Up to 24 months
Safety Issue:
Description:ECOG performance status will be assessed.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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