Pembrolizumab and Concurrent Chemoradiotherapy or Radiation Therapy in Treating Patients With Small Cell Lung Cancer
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| ClinicalTrials.gov Identifier: NCT02402920 |
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Recruitment Status :
Recruiting
First Posted : March 30, 2015
Last Update Posted : November 29, 2018
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Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
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Brief Summary:
This phase I trial studies the side effects and best dose of pembrolizumab when given together with chemoradiotherapy or radiation therapy in treating patients with small cell lung cancer. 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. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more cancer cells. Giving pembrolizumab with chemoradiotherapy or radiation therapy may be a better treatment for small cell lung cancer.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Extensive Stage Small Cell Lung Carcinoma Limited Stage Small Cell Lung Carcinoma Neuroendocrine Neoplasm | Drug: Carboplatin Drug: Cisplatin Drug: Etoposide Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Procedure: Radiation Therapy | Phase 1 |
PRIMARY OBJECTIVES:
I. Safety of pembrolizumab (MK 3475) plus chemotherapy (chemo)/radiation for limited-stage small-cell lung cancer (LS-SCLC).
II. Safety of MK-3475 plus radiation for extensive-stage small-cell lung cancer (ES-SCLC).
SECONDARY OBJECTIVES:
I. MK-3475 will improve progression free survival (PFS) compared to historical controls for LS-SCLC and ES-SCLC.
OUTLINE: This is a dose-escalation study of pembrolizumab. Patients are assigned to either Part A or Part B based on diagnosis.
PART A (LS-SCLC): Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and undergo radiation therapy twice daily (BID) 5 days a week for 3 weeks. Patients also receive cisplatin IV over 2 hours or carboplatin IV over 30 minutes and etoposide IV over 4 hours on days 1, 2, and 3. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy, 4 courses for chemotherapy) in the absence of disease progression or unacceptable toxicity. Patients who achieve systemic disease control and do not exhibit severe (grade > 3) pembrolizumab related toxicity during/after completion of 16 courses may receive 16 additional courses of pembrolizumab in the absence of disease progression or unacceptable toxicity.
PART B (ES-SCLC): Beginning after the completion of chemotherapy, patients receive pembrolizumab IV over 30 minutes on day 1 and undergo radiation therapy BID 5 days a week for 3 weeks. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, all patients are followed up at 30 days and then every 12 weeks.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 80 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase I Trial of MK-3475 and Concurrent Chemo/Radiation for the Elimination of Small Cell Lung Cancer |
| Actual Study Start Date : | July 22, 2015 |
| Estimated Primary Completion Date : | July 31, 2023 |
| Estimated Study Completion Date : | July 31, 2023 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Lung cancer
MedlinePlus related topics:
Lung Cancer
Drug Information available for:
Pembrolizumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part A (LS-SCLC, pembrolizumab, chemoradiotherapy)
Patients receive pembrolizumab IV over 30 minutes on day 1 and undergo radiation therapy BID 5 days a week for 3 weeks. Patients also receive cisplatin IV over 2 hours or carboplatin IV over 30 minutes and etoposide IV over 4 hours on days 1, 2, and 3. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy, 4 courses for chemotherapy) in the absence of disease progression or unacceptable toxicity. Patients who achieve systemic disease control and do not exhibit severe (grade > 3) pembrolizumab related toxicity during/after completion of 16 courses may receive 16 additional courses of pembrolizumab in the absence of disease progression or unacceptable toxicity.
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Drug: Carboplatin
Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Biological: Pembrolizumab Given IV
Other Names:
Procedure: Radiation Therapy Undergo radiation therapy
Other Names:
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Experimental: Part B (ES-SCLC, pembrolizumab, radiation therapy)
Beginning after the completion of chemotherapy, patients receive pembrolizumab IV over 30 minutes on day 1 and undergo radiation therapy BID 5 days a week for 3 weeks. Treatment repeats every 3 weeks for 16 courses (1 course for radiation therapy) in the absence of disease progression or unacceptable toxicity.
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Other: Laboratory Biomarker Analysis
Correlative studies Biological: Pembrolizumab Given IV
Other Names:
Procedure: Radiation Therapy Undergo radiation therapy
Other Names:
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Primary Outcome Measures :
- Maximum tolerated dose of pembrolizumab with concurrent chemoradiation determined by dose limiting toxicities graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Part A) [ Time Frame: Up to 22 days after therapy initiation ]Frequency of adverse events will be tabulated by grade, type, and dose/cohort. Relative frequencies and confidence intervals will also be constructed.
- Maximum tolerated dose of pembrolizumab with concurrent radiation determined by dose limiting toxicities graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Part B) [ Time Frame: Up to 22 days after therapy initiation ]Frequency of adverse events will be tabulated by grade, type, and dose/cohort. Relative frequencies and confidence intervals will also be constructed.
Secondary Outcome Measures :
- Response rate [ Time Frame: Up to 8 years ]Will be performed using Global Immune Related Response Criteria that factors all indexed and non-indexed lesions, In-Field Immune Related Response Criteria in which only non-radiation therapy-treated lesions and non-index lesions arising outside the radiation therapy planning target volume will be considered, and Out-Field Immune Related Response Criteria in which only non-radiation therapy-treated lesions and non-index lesions arising outside the radiation therapy planning target volume will be considered.
- Progression free survival [ Time Frame: Up to 8 years ]Time to event distributions for progression free survival will be estimated via Kaplan-Meier analysis.
- Overall survival [ Time Frame: Up to 8 years ]Time to event distributions for overall response will be estimated via Kaplan-Meier analysis.
- Biomarker response [ Time Frame: Up to 8 years ]Descriptive analysis will include a global assessment of patient outcomes for parts A and B separately.
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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 a performance status of 0 or 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 10 days of treatment initiation)
- Platelets >= 100,000/mcL (performed within 10 days of treatment initiation)
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (performed within 10 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 (creatinine clearance should be calculated per institutional standard) (performed within 10 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 10 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 metastatic malignant neoplasm in the liver (liver metastases) (performed within 10 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, 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 10 days of treatment initiation)
- Female subjects 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
- Histologic diagnosis of either limited stage SCLC (LS-SCLC), or extensive stage SCLC (ES-SCLC) or neuroendocrine tumor
Exclusion Criteria:
- Is currently participating in or has participated in a study of an investigational agent (except glutamine) or using an investigational device within 2 weeks of the first dose of treatment
- 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; with the exception of physiologic steroid replacement
- Has had a prior monoclonal antibody within 2 weeks prior to study day 1 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, within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent; prior radiation does not require a washout period; 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 skin basal cell carcinoma (basal cell carcinoma of the skin), skin squamous cell carcinoma (squamous cell carcinoma of the skin), or in situ cervical cancer that has undergone potentially curative therapy
- 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
- 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 exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
- Has evidence of interstitial lung disease or 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-programmed cell death-1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation (CD)137
- 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 ribonucleic acid [HCV RNA] [qualitative] is detected)
- Has received a live vaccine within 30 days prior to the first dose of trial treatment
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): NCT02402920
Contacts
| Contact: James Welsh | 713-563-2300 | jwelsh@mdanderson.org |
Locations
| United States, Texas | |
| M D Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: James Welsh 713-563-2300 | |
| Principal Investigator: James Welsh | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | James Welsh | M.D. Anderson Cancer Center |
Additional Information:
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT02402920 History of Changes |
| Other Study ID Numbers: |
2014-1003 NCI-2015-00598 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2014-1003 ( Other Identifier: M D Anderson Cancer Center ) P30CA016672 ( U.S. NIH Grant/Contract ) |
| First Posted: | March 30, 2015 Key Record Dates |
| Last Update Posted: | November 29, 2018 |
| Last Verified: | November 2018 |
| 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 Small Cell Lung Carcinoma Lung Neoplasms Neuroendocrine Tumors Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases Neuroectodermal Tumors |
Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Cisplatin Carboplatin Pembrolizumab Etoposide Etoposide phosphate Podophyllotoxin Antineoplastic Agents Antineoplastic Agents, Immunological Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |