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Switch Maintenance Pembrolizumab in Patients With NSCLC After First Line Platinum Doublet Chemotherapy (SWIPE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02705820
Recruitment Status : Active, not recruiting
First Posted : March 11, 2016
Last Update Posted : January 27, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Haris Charalambous, Bank of Cyprus Oncology Centre

Brief Summary:
Single arm one stage Phase II study: post 4-6 cycles platinum doublet chemotherapy for patients with metastatic Non Small Cell Lung Cancer (NSCLC) offering Pembrolizumab as maintenance therapy to non-progressors with primary endpoint: Immune Related Progression Free Survival (irPFS) at 1 year. Aim to show that this is at least 25% (compared to an expected 12% 1 year PFS based on the Pemetrexed and Erlotinib maintenance trials).

Condition or disease Intervention/treatment Phase
Metastatic Non Small Cell Lung Cancer Drug: Pembrolizumab Phase 2

Detailed Description:

Rationale:

There are currently no data on maintenance therapy with PD1/PDL1 inhibitors in NSCLC. After an initial response / stable disease to first line chemotherapy, non progressors / candidates for maintenance treatment, represent an ideal setting / patient group to test the efficacy of Pembrolizumab given that chemotherapy results in antigen release, hence it has the potential to augment immune checkpoint blockade, and following disease cytoreduction, this represents a lower disease burden setting, that may suit checkpoint inhibition better given the recent studies in Prostate cancer with Ipilimumab and Melanoma with Pembrolizumab(suggesting better outcomes for patients with less extensive disease).

Primary endpoint: percentage of patients that have not progressed at 1 year using immune related radiological criteria.

All patients to be treated with fixed dose 200mg iv Pembrolizumab until unacceptable toxicity, disease progression or completion of 2 years therapy.

Statistical Analysis Plan Summary The study employs a one stage phase II Fleming's design using irPFS at 1 year as primary endpoint. Using response hypotheses of H0 < 12 % and Ha> 25% i.e. that the irPFS at 1 year for the maintenance Pembrolizumab arm is 25%, compared to 12% in the normal chemotherapy maintenance arm, with a significance level (i.e., the probability of rejecting H0 when it is true) α=0.05 and the power (i.e. the probability of deciding the regimen is active) is 0.8 when true response rate is 25%, 48 patients are required to be entered into this study.

Entry Criteria Diagnosis/Condition for Entry into the Trial In order to be eligible for trial entry, patients must have a diagnosis of metastatic Non Small Cell Lung Cancer, and should not have progressed after first line palliative chemotherapy with a platinum doublet. They should have received no more than six (6) cycles of a platinum doublet chemotherapy, and should be able to receive treatment within three (3) to six (6) weeks from the last chemotherapy administration.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Switch Maintenance Pembrolizumab in Patients With Non Small Cell Lung Cancer (NSCLC) Who do Not Progress After First Line Platinum Doublet Chemotherapy. (SWIPE)
Actual Study Start Date : April 25, 2016
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : July 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: single arm study
experimental treatment with maintenance pembrolizumab
Drug: Pembrolizumab
Switch maintenance pembrolizumab treatment
Other Name: MK-3475




Primary Outcome Measures :
  1. Immune Related Progression Free Survival (irPFS) at 1 year [ Time Frame: 1 years ]

Secondary Outcome Measures :
  1. Response rates using RECIST [ Time Frame: 2 years ]
  2. Response Rates with immune related Response Criteria (irRC) [ Time Frame: 2 years ]
  3. Radiological Progression Free Survival (PFS) using RECIST criteria [ Time Frame: 3 years ]
  4. Immune-related PFS using irRC [ Time Frame: 3 years ]
  5. Overall survival [ Time Frame: 3 years ]
  6. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 3 years ]


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:

  • In order to be eligible for participation in this trial, the subject must:

    1. Be willing and able to provide written informed consent/assent for the trial.
    2. Be above 18 years of age on day of signing informed consent.
    3. Have measurable disease based on RECIST 1.1.
    4. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
    5. Have a performance status of 0 to 2 on the ECOG Performance Scale.
    6. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.

      Table 1 Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN, AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Albumin >2.5 g/L Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) 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 ≤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.

    7. 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.
    8. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.

      Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

    9. Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria:

The subject must be excluded from participating in the trial if the subject:

  1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  2. Have completed more than six (6) cycles of first line platinum doublet chemotherapy or more than six (6) have elapsed from the last chemotherapy administration of the first line chemotherapy with platinum doublet.
  3. 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.
  4. Has a known history of active TB (Bacillus Tuberculosis)
  5. Hypersensitivity to pembrolizumab or any of its excipients.
  6. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 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.
  7. Has had prior chemotherapy, targeted small molecule therapy, or radiation 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.

    • 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.
  8. 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.
  9. 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.
  10. 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.
  11. Has known history of, or any evidence of active, non-infectious pneumonitis.
  12. Has an active infection requiring systemic therapy.
  13. 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.
  14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  15. 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.
  16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  19. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

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): NCT02705820


Locations
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Cyprus
Bank of Cyprus Oncology Centre
Nicosia, Strovolos, Cyprus, 2006
Sponsors and Collaborators
Bank of Cyprus Oncology Centre
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Dr Haris Charalambous, BM MRCP FRCR Consultant Oncologist, BOC Oncology Centre
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Responsible Party: Haris Charalambous, Dr Haris Charalambous BM MRCP FRCR, Bank of Cyprus Oncology Centre
ClinicalTrials.gov Identifier: NCT02705820    
Other Study ID Numbers: 3475-449
First Posted: March 11, 2016    Key Record Dates
Last Update Posted: January 27, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Haris Charalambous, Bank of Cyprus Oncology Centre:
Metastatic, Lung Cancer, Switch, Maintenance, Pembrolizumab.
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents