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Phase I Trial of MK-3475 and Concurrent Chemo/Radiation for the Elimination of Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT02402920
Recruitment Status : Recruiting
First Posted : March 30, 2015
Last Update Posted : May 23, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of pembrolizumab (also called MK-3475) and radiation therapy (either with chemotherapy or alone) that can be given to patients with SCLC.

This is an investigational study. Radiation therapy is delivered using FDA-approved and commercially available methods for local control of metastatic and primary tumors. Pembrolizumab is FDA approved and commercially available for the treatment of unresectable or metastatic melanoma. It use in this study is investigational.

Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Lung Cancer Drug: Etoposide Drug: Cisplatin Drug: Carboplatin Drug: MK-3475 Radiation: Radiation Therapy Phase 1

Detailed Description:

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a part and study group based on when you join this study. Up to 3 groups of 3 participants each will be enrolled in Part A and up to 80 participants will be enrolled in Part B.

If you are enrolled in Part A or B, the dose of pembrolizumab you receive will depend on when you join this study. The first group of participants will receive the lowest dose level of pembrolizumab. Each new group will receive a higher dose of pembrolizumab than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of pembrolizumab is found. All participants will receive pembrolizumab during radiation therapy. The radiation will be to the chest area. In addition to pembrolizumab, participants in Part A will also receive either cisplatin and etoposide or carboplatin and etoposide.

Study Drug Administration:

You will receive pembrolizumab by vein over about 30 minutes on Day 1 of each 3-week cycle.

If you are in Group A, on Day 1 of Cycles 1-32, you will receive pembrolizumab by vein over 30 minutes. In addition, on Day 1 of Cycles 1-4, you will receive cisplatin by vein over about 2 hours and etoposide by vein over 4 hours on Days 1, 2, and 3. If you are unable to tolerate cisplatin, you will receive carboplatin by vein over 30 minutes and etoposide by vein over 4 hours on Days 1, 2, and 3.

Study Visits:

When you are not receiving radiation, you will have these every 3 weeks.

  • You will have a physical exam.
  • Blood (about 1 tablespoon) may be drawn for routine tests.

Follow Up:

Every 12 weeks after your last dose of pembrolizumab, you will have CT or PET scans to check the status of the disease. You will also have PFTs performed. If you are unable to make these visits, you will be contacted by phone to check your health.

Length of Study:

You may continue taking the study drug for up to 32 doses. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: 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 2015
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Limited Stage SCLC Group: MK-3475 + Radiation

Part A: Participants receive MK-3475 by vein on Day 1 of Cycles 1-16. The dose of MK-3475 given by vein depends on when the participants joins this study.

Participants receive chemotherapy with either Cisplatin and Etoposide or Carboplatin and Etoposide. During cycles 1-4, Etoposide 100 mg/m^2 given by vein on Days 1, 2, and 3 of each 3 week cycle. During cycles 1-4 of the induction phase, participants for whom Cisplatin/Etoposide has been selected as chemotherapy receive Cisplatin 80 mg/m^2 by vein on Day 1 of each 3 week cycle. Cisplatin given for up to four cycles.

During cycles 1-4 of the induction phase, participants for whom Carboplatin/Etoposide has been selected as chemotherapy receive Carboplatin by vein at AUC 5 on Day 1 of each 3 week cycle. Carboplatin given for up to four cycles.

Radiation therapy delivered to chest at 45 Gy twice a day for 15 days.

Drug: Etoposide
100 mg/m^2 given by vein on Days 1, 2, and 3 of each 3 week cycle.
Other Name: VePesid

Drug: Cisplatin
80 mg/m^2 by vein on Day 1 of each 3 week cycle.
Other Names:
  • Platinol-AQ
  • Platinol
  • CDDP

Drug: Carboplatin
AUC 5 by vein on Day 1 of each 3 week cycle.
Other Name: Paraplatin

Drug: MK-3475

Limited Stage SCLC MK-3475 + Radiation Group - Part A: MK-3475 given by vein on Day 1 of every 3 week cycle. The first group of participants will receive the lowest dose level of MK-3475. Each new group will receive a higher dose of MK-3475 than the group before it until maximum tolerated dose achieved.

Extensive Stage SCLS MK-3475 + Radiation Group Part B: MK-3475 given by vein Day 1 of every 3 week cycle. The first group of participants will receive the lowest dose level of MK-3475. Each new group will receive a higher dose of MK-3475 than the group before it until maximum tolerated dose achieved.

Other Names:
  • Keytruda
  • Pembrolizumab
  • SCH-900475

Radiation: Radiation Therapy

Limited Stage SCLC MK-3475 + Radiation Group: Radiation therapy delivered to chest at 45 Gy twice a day for 15 days.

Extensive Stage SCLS MK-3475 + Radiation Group: Radiation therapy delivered to chest at 45 Gy once a day for 15 days.

Other Name: XRT

Experimental: Extensive Stage SCLS Group: MK-3475 + Radiation
Part B: After second chemotherapy cycle, the dose of MK-3475 given by vein will depend on when the participants joins this study. Consolidation radiation therapy delivered after 1-6 cycles of chemotherapy. Radiation therapy delivered to chest at 45 Gy once a day for 15 days.
Drug: MK-3475

Limited Stage SCLC MK-3475 + Radiation Group - Part A: MK-3475 given by vein on Day 1 of every 3 week cycle. The first group of participants will receive the lowest dose level of MK-3475. Each new group will receive a higher dose of MK-3475 than the group before it until maximum tolerated dose achieved.

Extensive Stage SCLS MK-3475 + Radiation Group Part B: MK-3475 given by vein Day 1 of every 3 week cycle. The first group of participants will receive the lowest dose level of MK-3475. Each new group will receive a higher dose of MK-3475 than the group before it until maximum tolerated dose achieved.

Other Names:
  • Keytruda
  • Pembrolizumab
  • SCH-900475

Radiation: Radiation Therapy

Limited Stage SCLC MK-3475 + Radiation Group: Radiation therapy delivered to chest at 45 Gy twice a day for 15 days.

Extensive Stage SCLS MK-3475 + Radiation Group: Radiation therapy delivered to chest at 45 Gy once a day for 15 days.

Other Name: XRT




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of MK 3475 [ Time Frame: 3 weeks ]
    If 1/6 patients has grade 3 or higher toxicity then escalation proceeds, if 2/6 has grade 3 or greater toxicity then this is declared MTD.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 12 weeks after last dose of Pembrolizumab ]
    Response and progression evaluated using guidelines proposed by the Immune Related Response Criteria (irRC). Patients with measurable disease also assessed using standard RECIST v 1.1 and World Health Organization (WHO) treatment response criteria.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Be willing and able to provide written informed consent/assent for the trial
  2. Be >/= 18 years of age on day of signing informed consent
  3. Have a performance status of 0 or 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  4. Demonstrate adequate organ function as defined here, all screening labs should be performed within 10 days of treatment initiation: Adequate Organ Function Laboratory Values- * Hematological; Absolute neutrophil count (ANC) >/=1,500 /mcL, Platelets >/=100,000 / mcL, Hemoglobin >/=9 g/dL or >/=5.6 mmol/L * Renal; 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] *Hepatic; 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
  5. Inclusion #5 continued: alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) </=2.5 X ULN or </=5 X ULN for subjects with liver metastases *Coagulation; International Normalized Ratio (INR) or Prothrombin Time (PT) </=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, 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
  6. 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.
  7. 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.
  8. 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.
  9. Histologic diagnosis of either limited state SCLC (LS-SCLC), or Extensive stage SCLC (ES-SCLC) or neuroendocrine tumor.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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 Sjorgen's syndrome will not be excluded from the study.
  8. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  9. Has an active infection requiring systemic therapy.
  10. 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.
  11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  12. 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.
  13. 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-CD137
  14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  15. 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)
  16. 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, MD 713-563-2300

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: James Welsh, MD 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: NCI CTRP )
First Posted: March 30, 2015    Key Record Dates
Last Update Posted: May 23, 2018
Last Verified: May 2018

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

Keywords provided by M.D. Anderson Cancer Center:
Lung Cancer
Small Cell Lung Cancer
SCLC
Limited-Stage Small-Cell Lung Cancer
LS-SCLC
Extensive-Stage Small-Cell Lung Cancer
ES-SCLC
MK-3475
Keytruda
Pembrolizumab
SCH-900475
Etoposide
VePesid
Cisplatin
Platinol-AQ
Platinol
CDDP
Carboplatin
Radiation therapy
XRT

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Etoposide phosphate
Cisplatin
Carboplatin
Etoposide
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action