Clinical Trials /

Atezolizumab With Neoadjuvant Chemotherapy for Patients With Newly-Diagnosed Advanced-Stage Ovarian Cancer

NCT03394885

Description:

The main purpose of this study is to validate a safe dose of atezolizumab with dose-dense paclitaxel and carboplatin when utilized with neoadjuvant chemotherapy and interval cytoreductive surgery followed by maintenance atezolizumab in women with advanced ovarian cancer.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab With Neoadjuvant Chemotherapy for Patients With Newly-Diagnosed Advanced-Stage Ovarian Cancer
  • Official Title: Atezolizumab in Combination With Neoadjuvant Chemotherapy and Interval Cytoreductive Surgery for Patients With Newly-Diagnosed Advanced-Stage Epithelial Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: Pro00079313
  • NCT ID: NCT03394885

Conditions

  • Ovarian Cancer
  • Ovarian Neoplasms

Interventions

DrugSynonymsArms
AtezolizumabTecentriqAtezolizumab with Carboplatin and Paclitaxel
CarboplatinParaplatinAtezolizumab with Carboplatin and Paclitaxel
PaclitaxelTaxolAtezolizumab with Carboplatin and Paclitaxel

Purpose

The main purpose of this study is to validate a safe dose of atezolizumab with dose-dense paclitaxel and carboplatin when utilized with neoadjuvant chemotherapy and interval cytoreductive surgery followed by maintenance atezolizumab in women with advanced ovarian cancer.

Detailed Description

      This is a Phase IB non-randomized, single-arm, open-label study of atezolizumab in
      combination with primary NACT-ICS in patients with advanced-stage epithelial ovarian cancer.
      The target population is women with previously untreated epithelial ovarian cancer (including
      fallopian tube and primary peritoneal cancer) with advanced stage (FIGO III-IV) disease
      suitable for NACT and ICS. The following regimen will be administered every 3 weeks for 3
      cycles prior to ICS, then for 3 cycles following ICS:

        -  Carboplatin AUC = 5 or 6 IV, D1 of each cycle

        -  Paclitaxel 70 to 80mg/m2 IV, over one hour, on D1, 8, 15 of each cycle

        -  Atezolizumab 1200mg IV D1 of each cycle of chemotherapy and will be continued as
           maintenance therapy every 3 weeks until there is a lack of clinical benefit,
           unacceptable toxicity, or a total duration of 18 months.

      Each cycle is 21 days in duration and will be administered in the outpatient setting. Limited
      individualized flexibility in dose assignment (as noted) is permitted per physician
      discretion in regards to advanced-stage disease, nutritional status, ascites, non-physiologic
      creatinine measurements, and other comorbidities.

      Three cycles of NACT with atezolizumab will be administered every 3 weeks prior to ICS
      (occurring between cycles 3 and 4) followed by 3 additional cycles (cycles 4-6) of
      chemotherapy with atezolizumab. Surgery must be performed after the third course of
      chemotherapy as soon as nadir counts permit, but preferably within six weeks after the
      completion of the third chemotherapy cycle. Fourth cycle of chemotherapy is to be
      administered as soon as possible, but preferably no more than six weeks after ICS.

      Safety monitoring, including assessment for irAEs, will occur at each cycle and for 90 days
      after the last administration of atezolizumab or until start of next anti-cancer regimen,
      whichever occurs first. Image assessment by CT scan or MRI will be performed at baseline,
      prior to ICS to assess response, after completion of 6 cycles of chemotherapy with
      atezolizumab to assess response at end of chemotherapy treatment, and as clinically indicated
      during the maintenance phase and after completion of study treatment to assess PFS. Disease
      progression/recurrence will be defined per RECIST criteria and will not include isolated
      asymptomatic progression on the basis of CA125 levels. Immune function analysis will be
      performed on blood and tumor samples obtained at two time points: 1. confirmatory biopsy
      prior to start of therapy and 2. ICS.

      It is estimated that 40 patients will be enrolled at an accrual rate of 3-5 patients/month
      and followed for a median of 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab with Carboplatin and PaclitaxelExperimentalAtezolizumab administered over 90 (± 15) minutes (for the first infusion, shortening to 60 (± 15) minutes and 30 ± 15) minutes for subsequent infusions as described below) followed by Paclitaxel 70-80mg/m2 IV administered over approximately one hour followed by Carboplatin IV administered over 15-30 minutes to achieve an initial target AUC of 5-6 mg/mL/Min (Calvert formula dosing).
  • Atezolizumab
  • Carboplatin
  • Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Signed Informed Consent Form (ICF)

          -  Ability and willingness to comply with the requirements of the study protocol

          -  Age ≥ 18 years

          -  No prior treatment for primary advanced (stage III or IV) epithelial ovarian,
             fallopian tube, or primary peritoneal carcinoma

          -  Confirmation of diagnosis (by surgical excisional/incisional biopsy or imaging-guided
             core biopsy), and patients for whom the plan of management will include NACT followed
             by ICS. The decision to proceed with NACT will be at the treating physician's
             discretion and include patients with advanced stage disease considered at low
             likelihood for optimal cytoreduction with primary debulking surgery.

          -  All patients must have measurable disease per RECIST v1.1

        Patients must meet the following criteria prior to initiation of study treatment:

          -  Histology consistent with high-grade epithelial ovarian cancer (excluding mucinous
             carcinoma, clear cell carcinoma, and carcinosarcoma)

          -  An adequate pre-treatment tumor biopsy is required to confirm histologic diagnosis.
             Acceptable options include laparoscopic biopsy or image-guided core needle biopsy
             (minimum of two cores). Fine needle aspiration (FNA) biopsy or cytology from ascites
             is not adequate.

          -  Adequate hematologic and end organ function, defined by the following laboratory
             results obtained within 14 days prior to the first study treatment

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 (see
             Appendix 6)

          -  Peripheral neuropathy less than or equal to CTCAE Grade 1

          -  For female patients of childbearing potential, agreement (by patient) to use highly
             effective form(s) of contraception (i.e., one that results in a low failure rate [< 1%
             per year] when used consistently and correctly) and to continue its use at least until
             ICS or if ICS is not performed then 90 days post last dose of atezolizumab

        Exclusion Criteria:

          -  Mucinous, low-grade histology, clear cell carcinoma, or carcinosarcoma

          -  Prior systemic chemotherapy for epithelial ovarian, fallopian tube, or primary
             peritoneal cancer.

          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3 years. (Exceptions include basal cell or squamous cell carcinoma of
             the skin, or in situ cervical cancer that has undergone potentially curative therapy.)

          -  AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for
             alopecia

          -  Bisphosphonate therapy for symptomatic hypercalcemia

          -  Known clinically significant liver disease, including active viral, alcoholic, or
             other hepatitis; cirrhosis; fatty liver; and inherited liver disease

          -  Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases

          -  Pregnancy, lactation, or breastfeeding

          -  Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  Inability to comply with study and follow-up procedures

          -  History or risk of autoimmune disease, including but not limited to systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
             syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune
             thyroid disease, vasculitis, or glomerulonephritis

          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
             tomography (CT) scan

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the patient at high risk from treatment
             complications

          -  History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C
             infection

          -  Active tuberculosis

          -  Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to
             hospitalization for complications of infection, bacteremia, or severe pneumonia

          -  Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1

          -  Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1

          -  Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or
             anticipation that such a live, attenuated vaccine will be required during the study

          -  Prior history of treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137,
             anti-CTLA4 or any other antibodies targeting co-stimulation or checkpoint pathways

          -  Treatment with systemic immunostimulatory agents (including but not limited to
             interferon [IFN] alpha or interleukin [IL]-2) within 6 weeks or five half-lives of the
             drug (whichever is shorter) prior to Cycle 1, Day 1

          -  Treatment with investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within
             five half lives of the investigational product, whichever is longer)

          -  Treatment with systemic immunosuppressive medications (including but not limited to
             prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor
             necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Patients with prior allogeneic bone marrow transplantation or prior solid organ
             transplantation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety: Incidence of post chemotherapy surgical debulking
Time Frame:9 weeks
Safety Issue:
Description:The ability of subjects to undergo interval cytoreductive surgery will be utilized as a measure of safety regarding the initial dosing of atezolizumab

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:18 months
Safety Issue:
Description:RECIST criteria will be utilized for subjects over the course of the study to measure their response to study drugs
Measure:Pathologic complete remission rate
Time Frame:9 weeks
Safety Issue:
Description:At interval cytoreduction pathologic complete remission rate will be measured using RECIST and immune-related response criteria.
Measure:Progression Free Survival
Time Frame:18 months
Safety Issue:
Description:All patients will be evaluated for progression free survival from the date of first treatment to the date of first observation of progressive disease or death due to any cause or will be stopped at date of last follow-up for those still alive without disease progression.
Measure:Overall survival
Time Frame:18 months
Safety Issue:
Description:All patients will be evaluated for overall survival from the date of first treatment on protocol to the date of death due to any cause and will be stopped at date of last follow-up for those still alive.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Duke University

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