viernes, 8 de julio de 2016

NCT02407171 Clinical Trial - National Cancer Institute || Pembrolizumab and Stereotactic Body Radiation Therapy in Treating Patients with Metastatic Melanoma or Non-small Cell Lung Cancer

NCT02407171 Clinical Trial - National Cancer Institute

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Pembrolizumab and Stereotactic Body Radiation Therapy in Treating Patients with Metastatic Melanoma or Non-small Cell Lung Cancer

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase II, Phase ITreatmentActive18 and over1411014879
NCI-2016-00944, NCT02407171

Trial Description

Summary

This phase Ib /IIa trial studies the side effects and best dose of stereotactic body radiation therapy when given together with pembrolizumab in treating patients with melanoma or non-small cell lung cancer that has spread to other places in the body. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Monoclonal antibodies, such as pembrolizumab, may block specific proteins which may strengthen the immune system and control tumor growth. Giving stereotactic body radiation therapy may prolong the response to pembrolizumab in patients with melanoma or non-small cell lung cancer.

Further Study Information

PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of stereotactic body radiation therapy (SBRT) to lung (Arm A) and non-lung (Arm B) targets in patients receiving pembrolizumab (MK-3475). (Phase Ib)
II. To determine the overall response rate to post-radiation MK-3475, in patients whose disease had previously progressed on MK-3475. (Phase IIa)
SECONDARY OBJECTIVES:
I. To determine the local control of SBRT, when SBRT is given with MK-3475.
II. To determine the time to progression in patients receiving post-radiation MK-3475, in patients whose disease had previously progressed on MK-3475.
III. To determine the progression-free and overall survival in patients MK-3475, who receive SBRT.
IV. To determine the safety and toxicity of the combination of SBRT and MK-3475.
V. To examine potential predictive biomarkers in tumor samples and peripheral blood in patients treated with MK-3475 and SBRT.
OUTLINE: This is a phase Ib, dose-escalation study of SBRT followed by a phase IIa study. Patients are assigned to 1 of 2 arms.
ARM A (NON-SMALL CELL LUNG CANGER [NSCLC]): Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days for up to 18 months in the absence of disease progression or unacceptable toxicity. After progression of disease, patients undergo SBRT. Patients then receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days for up to 18 months in the absence of disease progression or unacceptable toxicity.
ARM B (MELANOMA): Patients undergo SBRT. Patients then receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days for up to 18 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.

Eligibility Criteria

Inclusion Criteria:
Be willing and able to provide written informed consent/assent for the trial
Have metastatic melanoma or NSCLC, or locally advanced NSCLC not suitable for curative-intent local therapy
For melanoma patients, patients must have received prior programmed cell death protein 1 (PD-1) therapy and have progressed immune-related progressive disease (irPD) by immune-related Response Criteria (irRC)
Have 2 or more measurable sites of disease as defined by either Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or cutaneous lesions at least 1 cm in greatest dimension
Have at least one site of disease that is considered potentially suitable for treatment with SBRT
Have provided tissue from an archival or newly obtained tissue sample of a tumor lesion, sufficient for analysis of programmed cell death 1 ligand 1 (PD-L1) and other biomarkers; patients who have had PD-L1 analysis previously performed at Merck can substitute earlier analysis results and are not required to submit additional tissue for PD-L1 testing; expression of PD-L1 is NOT required for study entry
Have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
Absolute neutrophil count (ANC) >= 1,500 /mcL
Platelets >= 100,000 /mcL
Hemoglobin >= 9 g/dL
Serum creatinine <= 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
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
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
Exclusion Criteria:
NSCLC patients who have received prior therapy with an agent directed at PD-1, PD-L1, or programmed cell death 1 ligand 2 (PD-L2)
Has had systemic corticosteroids within 2 weeks of the first dose of protocol-related radiation or MK-3475
Has had radiation therapy within 2 weeks of the first protocol treatment
Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 2 weeks of the first protocol treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks of the first protocol treatment; the use of low-dose steroids for management of chronic conditions is allowed
Non-small cell lung cancer patients only: has had a prior monoclonal antibody within 4 weeks prior to first protocol treatment or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of the first protocol treatment or who 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: Patients who have had prior treatments with tyrosine kinase inhibitors (e.g. Tarceva) require only a 72-hour washout period prior to starting protocol treatment
Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
Has known active and untreated brain (central nervous system [CNS]) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate
Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an example of an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; those with a history of hypothyroidism who are now stable on hormone replacement will not be excluded; those with Sjorgen’s syndrome will not be excluded from the study
Has evidence of interstitial lung disease, active non-infectious pneumonitis, or a history of grade 3 or greater pneumonitis
Has an active infection requiring systemic therapy
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 screening visit through 120 days after the last dose of trial treatment
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Has known active hepatitis B (e.g., hepatitis B virus 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 prior to the first protocol treatment

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Yale University

  • National Cancer Institute
Roy H. Decker, Principal Investigator

Trial Sites

U.S.A.

Connecticut
New Haven
Yale University
Roy H. Decker
Ph: 203-737-2758
Email: roy.decker@yale.edu
Roy H. Decker
Principal Investigator
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.

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