Clinical Trials /

The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial.

NCT03523702

Description:

The goal of this study is to explore if, for locally advanced non-small cell lung cancer patients whose tumors have high levels of PD-L1 (a marker associated with benefits from immunotherapy), a combination of immunotherapy and a personalized 4-week radiotherapy course could be more effective than standard treatment, which is a combination of chemotherapy and radiotherapy.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial.
  • Official Title: The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial (SPRINT)

Clinical Trial IDs

  • ORG STUDY ID: 2018-8945
  • NCT ID: NCT03523702

Conditions

  • Non-small Cell Lung Cancer, NSCLC

Interventions

DrugSynonymsArms
PembroRTPembroRT Cohort
ChemoRTChemoRT Cohort

Purpose

The goal of this study is to explore if, for locally advanced non-small cell lung cancer patients whose tumors have high levels of PD-L1 (a marker associated with benefits from immunotherapy), a combination of immunotherapy and a personalized 4-week radiotherapy course could be more effective than standard treatment, which is a combination of chemotherapy and radiotherapy.

Detailed Description

      This is a Phase II trial evaluating the efficacy and safety of sequential pembrolizumab (200
      mg every three weeks) and accelerated, dose-painted radiotherapy for patients with locally
      advanced NSCLC with PD-L1 expression ≥ 50%. Patients with PD-L1 expression < 50% will also be
      enrolled and treated with standard concurrent chemoradiotherapy to serve as a non-randomized
      comparison group.
    

Trial Arms

NameTypeDescriptionInterventions
PembroRT CohortExperimentalSubjects with PD-L1 expression ≥ 50% Combination of pembrolizumab and dose-painted radiotherapy for locally advanced NSCLC patients with high (≥ 50%) PD-L1 expression.
  • PembroRT
ChemoRT CohortActive ComparatorSubjects with PD-L1 expression < 50% Subjects with PD-L1 expression below 50% will be enrolled and treated with standard concurrent chemoradiotherapy.
  • ChemoRT

Eligibility Criteria

        Inclusion Criteria:

        Participants are eligible to be included in the study only if all the following criteria
        apply:

          1. Male/female participants who are at least 18 years of age on the day of signing
             informed consent with histologically confirmed diagnosis of non-small cell lung cancer
             will be enrolled in this study.

          2. Previously untreated, pathologically proven NSCLC with measurable disease (at least 1
             unidimensional, radiographically measurable lesion based on RECIST v1.1) and one of
             the following stages: (prior resection for early stage disease is allowed)

               1. AJCC version 8 Stage II disease, medically or technically unresectable

               2. AJCC version 8 Stage III disease

          3. Whole body PET/CT within 42 days prior to study entry demonstrating hypermetabolic
             pulmonary lesion(s) and/or thoracic lymph node(s). If PET/CT was obtained more than 42
             days prior to study entry and is not repeated, CT within 28 days prior to study entry
             demonstrating no evidence of metastatic disease is required.

          4. MRI of the brain or head CT with contrast within 42 days prior to study entry.

          5. PFTs within 42 days of study entry

          6. ECOG performance status 0-1

          7. Adequate end-organ function, based on routine clinical and laboratory workup:

               1. ANC >1,500 cells/µl, Platelets ≥ 100,000 cells/µl, Hemoglobin ≥ 9.0 g/dl

               2. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min

               3. Total bilirubin ≤ 1.5 x ULN (or direct bilirubin below the ULN), AST and ALT ≤
                  2.5 x ULN

               4. International normalized ratio (INR) (or prothrombin time (PT)) and activated
                  partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving
                  anticoagulant therapy, as long as values are within the intended therapeutic
                  range

               5. Thyroid stimulating hormone (TSH) within normal limits. If TSH is not within
                  normal limits, the participant may be eligible if T3 and free T4 are within
                  normal limits.

          8. A female participant is eligible to participate if she is not pregnant (see Exclusion
             Criteria), not breastfeeding, and at least one of the following conditions applies:

               1. Not a woman of childbearing potential (WOCBP) as defined in the Appendix

               2. A WOCBP who agrees to follow the contraceptive guidance in the Appendix during
                  the treatment period and for at least 120 days after the last dose of study
                  treatment with pembrolizumab (pembroRT cohort) or at least 180 days after the
                  last dose of chemotherapy (chemoRT cohort).

          9. A male participant must agree to use contraception during the treatment period and for
             at least 28 days after the last dose of study treatment and refrain from donating
             sperm during this period.

         10. The participant (or legally acceptable representative if applicable) provides written
             informed consent for the trial.

        Exclusion Criteria:

        Participants are excluded from the study if any of the following criteria apply:

          1. Malignant pleural or pericardial effusion, based on clinical, imaging, or pathologic
             evaluation.

          2. Systemic therapy for lung cancer within the past year.

          3. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent
             directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40,
             CD137).

          4. Contraindication to protocol-specified radiotherapy, such as prior thoracic
             radiotherapy or active serious collagen vascular disease (e.g. scleroderma).

          5. Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment.

          6. Active malignancy other than lung cancer that requires active treatment other than
             hormonal therapy or is deemed by the treating physicians to be likely to affect the
             subject's survival duration.

          7. A history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

          8. Active infection requiring antimicrobial therapy.

          9. Has a known history of active TB (Bacillus Tuberculosis).

         10. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for

             the full duration of the study, 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. Pregnancy, assessed in WOCBP (defined in Appendix) with urine pregnancy test within 72
             hours prior to study treatment allocation. If urine pregnancy test is positive or
             cannot be confirmed as negative, a serum pregnancy test is required. If more than 72
             hours elapse between screening pregnancy test and the first dose of study treatment,
             another pregnancy test (urine or serum) must be performed and must be negative.

         13. For patients receiving pembrolizumab/radiotherapy

               1. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
                  excipients.

               2. Active autoimmune disease other than vitiligo, thyroid disorders, Sjogren's
                  disease, and well-controlled rheumatoid arthritis not requiring disease-modifying
                  therapy.

               3. Has received a live vaccine within 30 days prior to the first dose of study drug.
                  Examples of live vaccines include, but are not limited to, the following:
                  measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies,
                  Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines
                  for injection are generally killed virus vaccines and are allowed; however,
                  intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and
                  are not allowed.

               4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid
                  therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other
                  form of immunosuppressive therapy within 7 days prior to the first dose of study
                  drug.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival
Time Frame:18 months
Safety Issue:
Description:To characterize progression-free survival rates following treatment with sequential pembrolizumab and radiotherapy for locally advanced NSCLC with PD-L1 expression ≥ 50%.

Secondary Outcome Measures

Measure:Distant metastisis
Time Frame:18 months
Safety Issue:
Description:To characterize freedom from distant metastasis rates following treatment with sequential pembrolizumab and radiotherapy for locally advanced NSCLC with PD-L1 expression ≥ 50%.
Measure:Intrathoracic disease progression
Time Frame:18 months
Safety Issue:
Description:To characterize freedom from intrathoracic disease progression rates following treatment with sequential pembrolizumab and radiotherapy for locally advanced NSCLC with PD-L1 expression ≥ 50%.
Measure:Overall survival
Time Frame:18 months
Safety Issue:
Description:To characterize overall survival rates following treatment with sequential pembrolizumab and radiotherapy for locally advanced NSCLC with PD-L1 expression ≥ 50%.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Albert Einstein College of Medicine, Inc.

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