Clinical Trials /

A Phase III Study of Bevacizumab and Paclitaxel in Combination With Atezolizumab as a Treatment for Locally Advanced Unresectable or Metastatic Hormone Receptor-positive HER2 Negative Breast Cancer

NCT04732598

Description:

JCOG1919E (AMBITION) is a randomized, open-label, phase 3 trial to evaluate efficacy and safety of bevacizumab and paclitaxel in combination with atezolizumab comparing to bevacizumab and paclitaxel in patients with HR-positive HER2 negative metastatic breast cancer.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Phase III Study of Bevacizumab and Paclitaxel in Combination With Atezolizumab as a Treatment for Locally Advanced Unresectable or Metastatic Hormone Receptor-positive HER2 Negative Breast Cancer
  • Official Title: A Phase III, Randomized Study of Bevacizumab and Paclitaxel in Combination With Atezolizumab as a Treatment for Patients With Locally Advanced Unresectable or Metastatic Hormone Receptor-positive HER2 Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: JCOG1919E
  • NCT ID: NCT04732598

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Paclitaxel + bevacizumab therapyArm A
Paclitaxel + bevacizumab + atezolizumabArm B

Purpose

JCOG1919E (AMBITION) is a randomized, open-label, phase 3 trial to evaluate efficacy and safety of bevacizumab and paclitaxel in combination with atezolizumab comparing to bevacizumab and paclitaxel in patients with HR-positive HER2 negative metastatic breast cancer.

Trial Arms

NameTypeDescriptionInterventions
Arm AActive Comparator
  • Paclitaxel + bevacizumab therapy
Arm BExperimental
  • Paclitaxel + bevacizumab + atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically diagnosed as breast cancer (invasive cancer).

          -  Histologically diagnosed as hormone receptor positive (at least one of ER and PgR is
             positive) and HER2 negative. However, if there are multiple specimens, the
             histological results of the most recent specimen that meets the eligibility criteria
             (1) and (2) should be used.

          -  Diagnosed with advanced recurrent breast cancer (either unresectable locally advanced
             breast cancer, recurrent breast cancer, or Stage IV breast cancer).

          -  Age 20 years or older on the date of registration. Either male or female are
             acceptable.

          -  ECOG performance status (PS) of 0-2.

          -  Patients must have measurable lesions.

          -  Hormone refractory[*1] or life-threatening metastases [*2].

               1. Hormone refractory: Recurrence within 2 years after the start of postoperative
                  endocrine therapy, or progression within 6 months of endocrine therapy for
                  advanced recurrent breast cancer.

               2. Life-threatening metastases: Symptomatic metastases that require symptomatic
                  relief through urgent tumor shrinkage. Examples include multiple liver
                  metastases, lung metastases, carcinomatous pleurisy, and carcinomatous
                  lymphangitis.

          -  PD-L1 status has been confirmed by a central measurement institute.

          -  No active brain metastases that require treatment.

          -  No history of prior chemotherapy treatment for advanced or recurrent breast cancer.
             However, in case that a history of preoperative/postoperative chemotherapy including
             paclitaxel or docetaxel, it is acceptable if at least 6 months have passed since the
             last dose.

          -  The most recent laboratory test within 14 days prior to enrollment (the same day of
             the week two weeks prior to the date of enrollment is acceptable) must meet all of the
             following

               1. Neutrophil count ≥1,500/mm^3

               2. Hemoglobin ≥ 9.0 g/dL (No blood transfusion within 14 days prior to the date of
                  blood collection for the test used for registration)

               3. Platelet count ≥10×104/mm^3

               4. Total bilirubin ≤ 1.5 mg/dL

               5. AST ≤ 100 IU/L (≤ 150 IU/L if liver metastasis is present)

               6. ALT ≤ 100 IU/L (≤ 150 IU/L in case of liver metastasis)

               7. Serum creatinine ≤1.2 mg/dL

               8. PT-INR ≤ 1.5, but PT-INR ≤ 3.0 if the patient is taking anticoagulants such as
                  warfarin prophylactically.

               9. Urine protein (test paper method) of 1+ or less

          -  For women of childbearing potential [*1], consent for contraception from the time of
             obtaining consent until at least 6 months after completion of the protocol treatment.
             For lactating patients, the patient agrees not to breastfeed from the start of
             protocol treatment until at least 6 months after the end of protocol treatment. For
             men, they agree to use contraception from the start of protocol treatment until at
             least 6 months after the end of protocol treatment [*2].

               1. Women of childbearing potential: Women who have experienced menarche, have not
                  undergone sterilization (hysterectomy or bilateral oophorectomy), and have not
                  undergone menopause. Menopause is defined as the absence of menstruation for more
                  than 12 months without another medical reason such as drug administration.

               2. Examples of contraceptive methods: condoms, pessaries, oral contraceptives, use
                  of intrauterine devices, etc.

          -  The patient's written consent to participate in the study has been obtained.

        Exclusion Criteria:

          -  Active multiple cancer. However, the following are excluded: ①Completely resected
             cancers: basal cell carcinoma, Stage I spinous cell carcinoma, intraepithelial
             carcinoma, intramucosal carcinoma, superficial bladder cancer, ② gastrointestinal
             tract cancer that has been curatively resected by ESD or EMR, and ③ other cancers that
             have not recurred for more than 5 years.

          -  Infectious diseases that require systemic treatment.

          -  Complicated active gastrointestinal ulcer.

          -  Patients must have poorly controlled hypertension (systolic blood pressure ≥150 mmHg
             and/or diastolic blood pressure ≥100 mmHg) despite the use of two or more
             antihypertensive agents.

          -  Patients must have symptomatic congestive heart failure, unstable angina, or
             arrhythmia requiring treatment at the time of enrollment.

          -  History of myocardial infarction within 1 year prior to enrollment.

          -  Major surgery or incisional biopsy or significant trauma within 28 days prior to
             enrollment; placement of a CV port is not considered major surgery.

          -  Patients with deep vein thrombosis or pulmonary embolism at the time of enrollment, or
             a history of such within 1 year prior to enrollment.

          -  Use of anticoagulants (except aspirin of 324 mg/day or less) within 10 days prior to
             enrollment.

          -  Patients with a history of idiopathic pulmonary fibrosis, organizing pneumonia
             (bronchiolitis obliterans, etc.), drug-induced pneumonitis, or idiopathic pneumonitis.
             However, patients with a history of drug-induced pneumonitis who are asymptomatic at
             the time of enrollment can be enrolled if they undergo regular chest X-ray
             examinations and careful follow-up including auscultation and medical examination.

          -  Findings of active pneumocystitis on chest CT. However, a history of localized
             radiation pneumonitis (fibrosis) in the irradiation field is inclusible.

          -  Patients have been treated with investigational atezolizumab, or other immune
             checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody drugs), or
             immunostimulants (e.g., interferon, interleukin-2).

          -  Active autoimmune disease, immunodeficiency, or history thereof (e.g., myasthenia
             gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
             arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's
             granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis,
             etc.). However, the following are inclusible. Patients with autoimmune hypothyroidism
             who are using a stable dose of thyroid hormone preparations. Patients with eczema,
             psoriasis, lichen simplex chronicus, or vitiligo vulgaris whose symptoms are limited
             to the skin, and whose rash accounts for less than 10% of the body surface area and is
             well controlled by topical application of low potency corticosteroids alone. No acute
             exacerbation of the underlying disease requiring solaren long-wavelength ultraviolet
             therapy, methotrexate, retinoids, biologics, oral calcineurin inhibitors, high potency
             or oral corticosteroids within the past 12 months.

          -  Patients who have received a live attenuated vaccine within 4 weeks prior to
             enrollment or are expected to require a live attenuated vaccine within 5 months of
             completion of protocol treatment.

          -  Patients have not recovered from clinically significant toxicity caused by previous
             therapy, except for alopecia and Grade 1 peripheral neuropathy.

          -  Hypersensitivity or contraindication to any component of the therapeutic agent,
             including macrogol glycerol ricinoleate (Cremophor®), an additive to paclitaxel.

          -  Positive for HIV antibodies, HBs antigen, or HCV antibodies (however, if HCV
             antibodies are positive but HCV-RNA is not detected, it is not excluded).

          -  Negative for HBs antigen, positive for HBs antibody or HBc antibody, and positive for
             HBV-DNA quantification.

          -  Women who are pregnant, lactating, or may be pregnant.

          -  Patients with psychosis or psychiatric symptoms that interfere with daily life and are
             judged to be difficult to participate in the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free Survival (investigator-assessed)
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression-free survival (blinded independent central review)
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Response rate (investigator-assessed)
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Duration of response (investigator-assessed)
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Response rate (blinded independent central review)
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Duration of response (blinded independent central review)
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Incidence of adverse events
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Incidence of serious adverse events
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Incidence of immune-related adverse events
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Progression-free survival in PD-L1 positive subpopulation (investigator-assessed)
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:PD- L1-positive subpopulation
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Progression-free survival in the PD-L1-positive subpopulation (investigator-assessed)
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Overall survival in the PD-L1-positive subpopulation
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Response rate in the PD-L1-positive subpopulation (investigator-assessed)
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:
Measure:Response rate in the PD-L1-positive subpopulation (blinded independent central review)
Time Frame:Up to 2years after last patient enrolled
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Japanese Foundation for Cancer Research

Last Updated

March 3, 2021