Atezolizumab Combined with Immunogenic Chemotherapy in Patients with Metastatic Triple-negative Breast Cancer

NCT03164993 | Completed Phase 2

• 1 other identifier: ML39079_ALICE
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 5

Brief Summary

This is a randomized, double-blind, placebo-controlled phase II study evaluating the safety and efficacy of Atezolizumab when combined with immunogenic chemotherapy in subjects with metastatic triple-negative breast cancer. Atezolizumab, pegylated liposomal doxorubicin and cyclophosphamide are the Investigational Medicinal Products (IMPs).

Conditions

Cancer, Breast; Triple Negative Breast Cancer

Keywords

Neoplasms

Outcome Measures

Primary Outcomes (2)

• Assessment of toxicity of combined treatment with Atezolizumab, pegylated liposomal doxorubicin and cyclophosphamide

  Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0 and Adverse Event of Special Interest (AESIs) for Atezolizumab

  From inclusion until last follow-up visit (12 weeks after end of treatment if progressive disease; 12 months after end of treatment if no disease progression)

• Progression-free survival (PFS)

  Descriptive comparison of the PFS rates in the total per protocol (PP) population, and the PD-L1+ PP population

  3 years

Secondary Outcomes (10)

• Objective tumor response rate

  3 years

• Overall survival

  5 years

• Duration of response

  3 years

• Durable tumor response rate (DRR; >6 months)

  3 years

• Patient reported outcome Farigue

  3 years

Other Outcomes (4)

• Assessment of immunological response

  3 years

• Identification of novel and integrated biomarkers

  3 years

• Characterization of tumor evolution induced by the study therapy

  3 years

Study Arms (2)

Arm Chemotherapy + Placebo

PLACEBO COMPARATOR

Chemo (pegylated liposomal doxorubicin + cyclophosphamide) + placebo

Drug: Pegylated liposomal doxorubicin; Drug: Cyclophosphamide; Other: Placebo

Arm Chemotherapy + Atezolizumab

ACTIVE COMPARATOR

Chemo (pegylated liposomal doxorubicin + cyclophosphamide) + Atezolizumab

Drug: Atezolizumab; Drug: Pegylated liposomal doxorubicin; Drug: Cyclophosphamide

Interventions

Atezolizumab DRUG

Atezolizumab is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, Atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.

Also known as: Tecentriq

Arm Chemotherapy + Atezolizumab

Pegylated liposomal doxorubicin DRUG

Chemotherapy

Arm Chemotherapy + Atezolizumab; Arm Chemotherapy + Placebo

Cyclophosphamide DRUG

Chemotherapy

Arm Chemotherapy + Atezolizumab; Arm Chemotherapy + Placebo

Placebo OTHER

Placebo

Arm Chemotherapy + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adequate newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. No anti-tumor treatment is allowed between the time point for biopsy and study entry. If a patient has undergone chemotherapy in the metastatic setting, a new biopsy must be obtained after this therapy
• Measurable disease according to iRECIST
• Signed Informed Consent Form
• Women or men aged ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• In patients that have received (neo)adjuvant treatment with anthracyclines or cyclophosphamide, a minimum of 12 months from treatment with anthracyclines or cyclophosphamide until relapse of disease is required
• A maximum of one previous line with chemotherapy in the metastatic setting
• Female subject of childbearing potential should have a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential should agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year, during the treatment period and for at least 5 months after the last dose of study therapy. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, proper use of hormonal contraceptives that inhibit ovulation and hormone-releasing intrauterine devices (IUDs). Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study therapy
• Able to swallow orally administrated medication.
• Adequate organ function as defined in Table 1 in the protocol.

You may not qualify if:

• Malignancies other than breast cancer within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer)
• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \> 2 weeks prior to randomization
• Known CNS disease, except for asymptomatic CNS metastases, provided all of the following criteria are met:
• Measurable disease outside the CNS
• No metastases to mesencephalon, pons, medulla oblongata, or spinal cord
• No ongoing requirement for dexamethasone as therapy for CNS disease
• No radiation of brain lesions within 7 days prior to randomization
• No leptomeningeal disease
• Patients with symptomatic CNS metastases must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may be eligible, if all other criteria are met
• Uncontrolled pleural effusion, pericardial effusion, or ascites. Patients with indwelling catheters (e.g., PleurX®) are allowed
• Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to randomization
• Ionized calcium \> 1.2 x UNL. The use of bisphosphonates is allowed
• Pregnant or breastfeeding
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
• Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina. Patients with a known left ventricular ejection fraction (LVEF) \< 40% will be excluded. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF \< 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate

Sponsors & Collaborators

• Oslo University Hospital: lead
• Hoffmann-La Roche: collaborator
• Norwegian Cancer Society: collaborator
• St. Olavs Hospital: collaborator
• Helse Stavanger HF: collaborator
• Rigshospitalet, Denmark: collaborator
• Vejle Hospital: collaborator
• NanoString Technologies, Inc.: collaborator
• Technical University of Denmark: collaborator
• Karolinska Institutet: collaborator

Study Sites (5)

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Vejle Sygehus

Vejle, 7100, Denmark

Location

Oslo University Hospital

Oslo, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

St. Olavs Hospital

Trondheim, Norway

Location

Related Publications (3)

• Rossevold AH, Andresen NK, Bjerre CA, Gilje B, Jakobsen EH, Raj SX, Falk RS, Russnes HG, Jahr T, Mathiesen RR, Lomo J, Garred O, Chauhan SK, Lereim RR, Dunn C, Naume B, Kyte JA. Atezolizumab plus anthracycline-based chemotherapy in metastatic triple-negative breast cancer: the randomized, double-blind phase 2b ALICE trial. Nat Med. 2022 Dec;28(12):2573-2583. doi: 10.1038/s41591-022-02126-1. Epub 2022 Dec 8.

  PMID: 36482103 BACKGROUND

• Svalheim KG, Andresen NK, Bjerre C, Gilje B, Jakobsen EH, Falk RS, Naume B, Kaasa S, Kyte JA. Patient-reported outcomes from the randomized ALICE trial evaluating the addition of atezolizumab to anthracycline-based chemotherapy in metastatic triple-negative breast cancer. Breast. 2026 Jan 19;86:104704. doi: 10.1016/j.breast.2026.104704. Online ahead of print.

  PMID: 41581361 DERIVED

• Kyte JA, Rossevold A, Falk RS, Naume B. ALICE: a randomized placebo-controlled phase II study evaluating atezolizumab combined with immunogenic chemotherapy in patients with metastatic triple-negative breast cancer. J Transl Med. 2020 Jun 23;18(1):252. doi: 10.1186/s12967-020-02424-7.

  PMID: 32576225 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms; Neoplasms

Interventions

atezolizumab; liposomal doxorubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jon Amund Kyte, M.D.-Ph.D.

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization will be performed using the eCRF. The subject will allocated to a randomization number and the randomization number will be sent to the hospital pharmacy. The pharmacy keeps the randomization listing and prepares the infusion according to the given randomization number. The pharmacy will keep a log of all infusions prepared. All other study personell will be blinded to the treatment code.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: National coordinating investigator

Model Details: Randomized, double-blind, placebo-controlled

Study Record Dates

• First Submitted: May 12, 2017
• First Posted: May 24, 2017
• Study Start: June 1, 2017
• Primary Completion: April 25, 2023
• Study Completion: September 30, 2023
• Last Updated: October 15, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2); NO (3)