Clinical Trials /

Staggered, Chemo-Immunotherapy With Durvalumab, MEDI4736 Pemetrexed & Carboplatin (PC) for Metastatic Non-Squamous NSCLC

NCT04163432

Description:

This is a Phase II, open label, randomized study of durvalumab in combination with pemetrexed and carboplatin in eligible adult patients with locally advanced or metastatic non-small cell lung cancer. The study will focus on the efficacy of two alternative staggered dosing regimens.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Staggered, Chemo-Immunotherapy With Durvalumab, MEDI4736 Pemetrexed & Carboplatin (PC) for Metastatic Non-Squamous NSCLC
  • Official Title: A Randomized, Phase II Study of Staggered, Chemo-Immunotherapy With Durvalumab, MEDI4736 Pemetrexed and Carboplatin (PC) for Metastatic Non-Squamous NSCLC

Clinical Trial IDs

  • ORG STUDY ID: HCI127115
  • NCT ID: NCT04163432

Conditions

  • Non-Small Cell Lung Cancer Metastatic

Interventions

DrugSynonymsArms
DurvalumabImfinziArm A: Chemo-Immuno
PemetrexedAlimtaArm A: Chemo-Immuno
CarboplatinArm A: Chemo-Immuno

Purpose

This is a Phase II, open label, randomized study of durvalumab in combination with pemetrexed and carboplatin in eligible adult patients with locally advanced or metastatic non-small cell lung cancer. The study will focus on the efficacy of two alternative staggered dosing regimens.

Detailed Description

      This trial will evaluated two different schedules of concurrent chemoimmunotherapy while
      simultaneously measuring immune activation, immune resistance and host factors. Both arms
      will consist of concurrent chemoimmunotherapy with durvalumab, pemetrexed and carboplatin,
      but in arm 1 the chemotherapy will precede the immunotherapy by a week and in arm 2 the
      immunotherapy will precede the chemotherapy by a week. Staggering these therapies still
      allows concurrent administration while allowing some degree of temporal isolation to better
      understand the contributions by chemotherapy and immunotherapy in this setting. Host and
      laboratory factors will be measured during treatment. We hypothesize that staggered dosing of
      immunotherapy in combination with chemotherapy can improve clinical benefit.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: Chemo-ImmunoExperimentalArmA receives chemotherapy on D1 and immunotherapy on D8 of a 28-day cycle for the first 2cycles. After the first 2cycles, patients on Arm A and Arm B will be administered chemotherapy and immunotherapy on D1 of a 21day cycle for cycles 3 and 4. After 4cycles of chemo-immunotherapy, patients receive maintenance therapy with durvalumab and pemetrexed until treatment discontinuation. Maintenance therapy is administered on D1 of a 21day cycle.
  • Durvalumab
  • Pemetrexed
  • Carboplatin
Arm B: Immuno-ChemoExperimentalArmB receives immunotherapy on D1 and chemotherapy on D8 of a 28-day cycle for the first 2cycles. After the first 2cycles, patients on Arm A and Arm B will be administered chemotherapy and immunotherapy on D1 of a 21day cycle for cycles 3 and 4. After 4cycles of chemo-immunotherapy, patients receive maintenance therapy with durvalumab and pemetrexed until treatment discontinuation. Maintenance therapy is administered on D1 of a 21day cycle.
  • Durvalumab
  • Pemetrexed
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female subject aged ≥ 18 years.

          -  Histologically or cytologically confirmed metastatic non-squamous non-small cell lung
             cancer.

          -  Patient has measurable disease as defined by RECIST 1.1 as assessed by either CT or
             MRI.

          -  Chemoimmunotherapy naïve (including durvalumab).

          -  ECOG Performance Status ≤ 2.

             --Note: If performance status = 2, ensure that there is a slot available prior to
             registration as only 20 PS = 2 patients will be enrolled on the protocol.

          -  Must have a life expectancy of at least 12 weeks.

          -  Adequate organ function as defined as:

               -  Hematologic:

                    -  White blood cell count > 2.0 g/dL

                    -  Platelet count ≥ 100,000/mm3

                    -  Hemoglobin ≥ 9 g/dL

                    -  Absolute neutrophil count (ANC) ≥ 1,500/mm3

               -  Hepatic:

                    -  Total Bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

                    -  Except for patients with Gilbert's syndrome.

                    -  AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN or ≤ 5 × institutional ULN if
                       liver metastases are present

               -  Renal:

                    -  eGFR ≥ 30 mL/min/1.73m2 or creatinine clearance ≥ 30 mL/min by
                       Cockcroft-Gault:

                    -  Males: ((140-age)×weight[kg])/(serum creatinine [mg/dL]×72)

                    -  Females: (((140-age)×weight[kg])/(serum creatinine [mg/dL]×72))×0.85

          -  Concurrent enrollment in the study, "Rethinking Measurement of Performance Status in
             Cancer Patients," IRB 112529.

          -  Concurrent enrollment in the study, "An Observational Study Assessing the Clinical
             Effectiveness of the VeriStrat® Test and Validating Immunotherapy Tests in Subjects
             with Non-Small Cell Lung Cancer," IRB 100314.

          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients. Women will be considered post-menopausal if they have
             been amenorrheic for 12 months without an alternative medical cause. The following
             age-specific requirements apply:

               -  Women <50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy or hysterectomy).

               -  Women ≥50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses >1 year ago, had
                  chemotherapy-induced menopause with last menses >1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy).

          -  Highly effective contraception for both male and female subjects throughout the study
             and for at least 3 months after the last dose of study therapy.

          -  Recovery to baseline or ≤ Grade 1 CTCAE v.5 from toxicities related to any prior
             treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive
             therapy.

          -  Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up.

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in this
             protocol. Written informed consent and any locally required authorization (eg, Health
             Insurance Portability and Accountability Act in the US, European Union [EU] Data
             Privacy Directive in the EU) obtained from the patient/legal representative prior to
             performing any protocol-related procedures, including screening evaluations.

        Exclusion Criteria:

          -  ALK or EGFR non-squamous non-small cell lung cancer.

          -  Prior radiation therapy within 2 weeks prior to cycle one day one.

             -Exception: Prior palliative radiotherapy is permitted, provided it has been completed
             at least 2 days prior to study enrollment and no clinically significant toxicities are
             expected.

          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the
             first dose of IP.

             -Note: Local surgery of isolated lesions for palliative intent is acceptable.

          -  History of allogenic organ transplantation.

          -  Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
             the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
             arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
             criterion:

               -  Patients with vitiligo or alopecia

               -  Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
                  hormone replacement

               -  Any chronic skin condition that does not require systemic therapy

               -  Patients without active disease in the last 5 years may be included but only
                  after consultation with the principal investigator

               -  Patients with celiac disease controlled by diet alone

          -  Current or prior use of immunosuppressive medication within 14 days of cycle one day
             one, EXCEPT for the following permitted steroids:

             --Intranasal, inhaled, topical steroids, eye drops or local steroid injection
             (eg,intra-articular injection);

               -  Systemic corticosteroids at physiologic doses ≤ 10mg/day of prednisone or
                  equivalent;

               -  Steroids as premedication for hypersensitivity reactions (eg, computed tomography
                  (CT) scan premedication).

          -  History of active primary immunodeficiency

          -  Diagnosis of any other malignancy within 2 years prior to study enrollment, except for
             adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the
             breast, bladder or of the cervix, and low-grade (Gleason 6 or below) prostate cancer
             on surveillance with no plans for treatment intervention (eg, surgery, radiation, or
             castration) or prostate cancer that has been adequately treated with prostatectomy or
             radiotherapy and currently with no evidence of disease or symptoms is allowed.

          -  Uncontrolled CNS metastases; subjects with previously treated brain metastases will be
             allowed if the brain metastases have been treated, toxicities have resolved to grade 1
             or baseline and steroids are no longer required.

             --Patients with asymptomatic brain metastasis are allowed if previous steroid
             treatment was discontinued ≥ 6 weeks.

          -  History of leptomeningeal carcinomatosis

          -  Uncontrolled intercurrent illness, including but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
             situations that would limit compliance with study requirement, substantially increase
             risk of incurring AEs or compromise the ability of the patient to give written
             informed consent

          -  Known HIV infection with a detectable viral load within 6 months of the anticipated
             start of treatment.

             -Note: Patients on effective anti-retroviral therapy with an undetectable viral load
             within 6 months of the anticipated start of treatment are eligible for this trial.

          -  Active infection including: tuberculosis (clinical evaluation that includes clinical
             history, physical examination and radiographic findings, and TB testing in line with
             local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or
             hepatitis C.

             -Note: Patients with a past or resolved HBV infection (defined as the presence of
             hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients
             positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction
             is negative for HCV RNA.

          -  Vaccination with a live vaccine within 30 days of cycle one day one and while on trial
             is prohibited except for administration of inactivated vaccines.

          -  Female patients who are pregnant or breastfeeding or male or female patients of
             reproductive potential who are not willing to employ effective birth control from
             screening to 90 days after the last dose of durvalumab monotherapy

          -  Known prior severe hypersensitivity to investigational product or any component in its
             formulations, including known severe hypersensitivity reactions to monoclonal
             antibodies, cisplatin, other platinum-containing compounds, or mannitol. (NCI CTCAE
             v5.0 Grade ≥ 3).

          -  Subjects taking prohibited medications as described in Section 6.5.2. A washout period
             of prohibited medications for a period of at least 5 half-lives or as clinically
             indicated should occur prior to the start of treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of clinical benefit
Time Frame:up to 5 years
Safety Issue:
Description:Described using RECIST 1.1 response criteria.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:up to 5 years
Safety Issue:
Description:Adverse events (AEs) and serious adverse events (SAEs) will be collected and assessed by CTCAE, v5.0 for assessment of safety and feasibility.
Measure:Objective response rate (ORR)
Time Frame:up to 5 years
Safety Issue:
Description:Assessed using RECIST 1.1
Measure:Progression free survival (PFS)
Time Frame:up to 5 years
Safety Issue:
Description:Assessed as the time between trial initiation and documented progression or radiographic imaging.
Measure:Overall survival (OS)
Time Frame:up to 5 years
Safety Issue:
Description:assessed as the time from trial initiation until death from any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

Last Updated

June 18, 2020