Clinical Trials /

Neoadjuvant Therapy of Pembrolizumab + Ramucirumab for PD-L1 Positive Stage IB-IIIA Lung Cancer (EAST ENERGY)

NCT04040361

Description:

The efficacy and safety of the neoadjuvant therapy of pembrolizumab+ ramucirumab

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Therapy of Pembrolizumab + Ramucirumab for PD-L1 Positive Stage IB-IIIA Lung Cancer (EAST ENERGY)
  • Official Title: Efficacy and Safety of Neoadjuvant Therapy of Pembrolizumab Combined With Ramucirumab for PD-L1 Positive Stage IB-IIIA Lung Cancer: An Open-label Single-arm Phase II Study

Clinical Trial IDs

  • ORG STUDY ID: EPOC1710
  • NCT ID: NCT04040361

Conditions

  • Non-small Cell Lung Cancer Stage IB
  • Non-small Cell Lung Cancer Stage II
  • Non-small Cell Lung Cancer Stage ⅢA

Interventions

DrugSynonymsArms
PembrolizumabMK3475Pembrolizumab+Ramucirumab+Surgery
RamucirumabLY3009806Pembrolizumab+Ramucirumab+Surgery

Purpose

The efficacy and safety of the neoadjuvant therapy of pembrolizumab+ ramucirumab

Detailed Description

      To demonstrate the antitumor activity and safety of neoadjuvant pembrolizumab plus
      ramucirumab followed by surgery in patients with PD-L1 positive stage IB-IIIA non-small cell
      lung cancer
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab+Ramucirumab+SurgeryExperimentalPembrolizumab and Ramucirumab will be administered simultaneously for non small cell lung cancer patients for 2 cycles before surgery.
  • Pembrolizumab
  • Ramucirumab

Eligibility Criteria

        Inclusion Criteria:

          1. Male/female participants who are at least 20 years of age on the day of signing
             informed consent

          2. Previously untreated and histologically proven NSCLC harboring PD-L1 expression (≥1%
             in a biopsy specimen), as measured by immunohistochemistry (22C3).

          3. Resectable clinical stage IB-IIIA NSCLC carefully evaluated by experienced thoracic
             surgeons. (If N2 disease is suspected, the histological or cytological confirmation is
             mandatory) (UICC version 8)

          4. Pulmonary resection more than lobectomy and lymph node dissection is considered to be
             possible for complete resection of the tumor.Be able to undergo protocol therapy,
             including necessary surgery.

          5. Has adequate pulmonary function for pulmonary resection. Predicted postoperative
             FEV1.0 is 800 mL or more. {(predicted postoperative FEV1.0) = (preoperative FEV1.0) x
             (18-number of resected segment) / 18}

          6. ECOG performance status of 0 to 1.

          7. Has measurable disease as defined by RECIST 1.1 as determined by investigator.

          8. Has adequate organ function as defined in the following criteria. Clinical test data
             must meet the following criteria within 14 days of the registration. The registration
             day is the standard, including the same day of the week two weeks prior.

             a Neutrophil count: ≥ 1500/mm3 b Hemoglobin (Hb) ≥ 9.0 g/dL c Platelet count: ≥ 10.0 ×
             104/mm3 d AST (SGOT) ≤ 100 IU/L e ALT (SGPT): ≤ 100 IU/L f Total bilirubin: ≤ 1.5
             mg/dL (Total bilirubin: ≤ 3.0 mg/dL for patient with Gilbert's syndrome) g Creatinine:
             CRE ≤ 1.5 mg/dL, or creatinine clearance of 40 mL/minute or higher [Even when the
             value is less than 40 mL/min in the Cockcroft-Gault equation, if the measured value
             from a 24-hour urine collection is 40 mL/min or higher, the patient qualifies.] *
             Cockcroft-Gault equation: Male: Ccr={(140-age) × body weight (kg)}/{72 × serum CRE
             value (mg/dL)}Female: Ccr=0.85 × {(140-age) × body weight (kg)}/{72 × serum CRE value
             (mg/dL) h SpO(2) ≥ 92% (room air) i International normalized ratio (INR) ≤ 1.5 j
             PTT(aPTT) ≤ 1.5 × ULN k Urinary protein ≤1+ (if it is ≥2+, store the urine for 24
             hours, and if the urinary protein is <1,000 mg, the patient is qualified).

          9. Female who are likely to become pregnant are negative with pregnancy tests (urine or
             serum) within 7 days prior to enrollment. They agree to conduct proper contraception
             (total abstinence, intrauterine contraceptive device, hormone release system, or
             contraceptive implant and oral contraceptive) for both men and women during the trial
             and from the final investigational dosing up to 120 days

         10. The participant (or legally acceptable representative if applicable) is willing and
             able to provide written informed consent/assent for the trial.

        Exclusion Criteria:

          1. Has one of the following tumor locations/types:

               -  NSCLC involving the superior sulcus

               -  Large cell neuro-endocrine cancer (LCNEC)

               -  Sarcomatoid tumor

               -  Synchronous lung cancer (within 5 years), current non-pure GGN on TSCT, or pure
                  GGN with 15mm or more on TSCT

          2. Has an active infection requiring systemic therapy.

          3. Has an active autoimmune disease that has required systemic treatment in past 2 years
             (ie, 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) is not considered a form
             of systemic treatment and is allowed.

          4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (dose
             exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive
             therapy within 7 days prior the first dose of trial drug.

          5. Has a known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          6. Hypersensitivity or allergy to pembrolizumab, ramucirumab, or any of their excipients.

          7. Has a known history of, or any evidence of active, interstitial lung disease.

          8. Has a hypertension that is difficult to control (systolic blood pressure ≥160 mmHg and
             diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive agents.

          9. Has an acute coronary syndrome (including myocardial infarction and unstable angina),
             and with a history of coronary angioplasty or stent placement performed within 6
             months before enrollment

         10. Has a history of New York Heart Association congestive heart failure of grade II or
             above, unstable angina, myocardial infarction within the past 6 months, or serious
             cardiac arrhythmia associated with significant cardiovascular impairment within the
             past 6 months

         11. Has a severe (hospitalization required) complications (intestinal palsy, intestinal
             obstruction, pulmonary fibrosis, diabetes difficult to control, heart failure,
             myocardial infarction, unstable angina, renal failure, liver failure, liver cirrhosis,
             mental disease, cerebrovascular disease etc).

         12. Has a known history of human immunodeficiency virus (HIV) infection. No HIV resting is
             required unless mandated by local health authority.

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

         14. Negative for HBs antigens, HBs antibodies, and HBc antibodies. However, if positive
             for HBs and/or HBc antibodies, the patient can be registered as long as they are
             negative for HBV-DNA.

         15. 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.

         16. Has a known additional malignancy that is progressing or requires active treatment
             within the past (5 years) or received anti-cancer drug including hormone therapy.

             Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
             the skin, bladder carcinoma, or carcinoma in situ (eg, in situ cervical cancer, breast
             carcinoma, CIS and AIS of the lung) that have undergone potentially curative therapy
             are not excluded.

         17. Has received a live vaccine within 30 days prior to the first dose of trial 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-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (eg, FluMist) are live attenuated vaccines and are not allowed.

         18. 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 (or longer as specified by local institutional guidelines) after the
             last dose of trial treatment.

         19. Has history of hemoptysis (more than 1/2 cups in teaspoon) in 2 months before
             registration, or invasion of major vessels by cancer or major vessel narrowing is
             recognized on the image.

         20. Image shows cavity formation in the tumor.

         21. Is considered highly likely to have complications related to bleeding.

             * Obvious tumor invasion to the chest great vessel, cavity formation of the lung
             lesion, or the existence of obvious thrombus on the image are recognized, etc.

         22. Has past history of gastrointestinal perforation, peptic ulcer, diverticulosis or
             fistula within 6 months.

             ※ As for peptic ulcer, registration is permitted when disease condition is controlled
             by appropriate treatment.

         23. Has a history of pulmonary embolism / deep vein thrombosis, or other thromboembolism
             within 3 months before registration.

         24. Received major surgery within 28 days before registration, or received procedures for
             placement of subcutaneous venous access devices within seven days before registration.

         25. Severe wounds, ulcers or fractures within 28 days before registration.

         26. Has undergone long-term treatment using aspirin, nonsteroidal anti-inflammatory drugs
             (such as ibuprofen, naproxen), dipyridamole, clopidogrel or similar drugs. However,
             use of aspirin up to 325 mg / day once a day is acceptable.

         27. Patients who are receiving anticoagulant therapy and whose dose of oral anticoagulant
             or low molecular weight heparin is not stable. In case of taking warfarin,
             registration is permitted if there is no active bleeding or no risk of bleeding with
             PT-INR being 3 or less.

         28. 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 registration.

             Note: Participants who have entered the follow-up phase of an investigational trial
             may participate as long as it has been 4 weeks after the last dose of the previous
             investigational agent.

         29. Has no intention to comply with the study protocol or it is impossible to comply.

         30. Investigator or clinical trial doctor judged unsuitable as subject of this trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major pathologic response (MPR) rate by central review
Time Frame:1 year 7 months
Safety Issue:
Description:Determination of major pathologic response rate is based on the method by Hellmann et al. on the pathological section. The percentage of residual tumor cells is calculated as viable tumor cells / tumor area × 100 (%). Tumor area includes viable tumor cells and interstitial tissue such as fibrosis, necrosis, and inflammatory cells.

Secondary Outcome Measures

Measure:Proportion of incidence of adverse events
Time Frame:1 year 7 months
Safety Issue:
Description:The incidences and types of adverse events that occur during neoadjuvant therapy and perioperative period (within postoperative 30 days and 90 days) will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measure:Major pathological response (MPR) rate by institutional report
Time Frame:1 year 7 months
Safety Issue:
Description:Determination of major pathologic response rate by institutional report
Measure:Pathological complete response rate (pCR rate)
Time Frame:1 year 7 months
Safety Issue:
Description:Pathological complete response rate (pCR rate)
Measure:Pathological complete resection rate (R0 rate)
Time Frame:1 year 7 months
Safety Issue:
Description:Pathological complete resection rate (R0 rate)
Measure:Objective response rate (ORR) according to RECIST and iRECIST
Time Frame:1 year 7 months
Safety Issue:
Description:Objective response rate (ORR) according to RECIST and iRECIST
Measure:Overall survival (OS)
Time Frame:5 years
Safety Issue:
Description:Overall survival (OS)
Measure:Recurrence-free survival (RFS)
Time Frame:5 years
Safety Issue:
Description:Recurrence-free survival (RFS)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Masahiro Tsuboi

Last Updated

May 1, 2020