Ipatasertib in Combination With Carboplatin, Carboplatin/Paclitaxel, or Capecitabine/Atezolizumab in Treating Patients With Metastatic Triple Negative Breast Cancer

NCT03853707 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 18496NCI-2019-00465
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies best dose of ipatasertib and how well it works with carboplatin with or without paclitaxel in treating patients with triple negative breast cancer that has spread to other places in the body (metastatic). Ipatasertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving ipatasertib in combination with carboplatin, carboplatin/paclitaxel, or capecitabine/atezolizumab will work better in treating patients with triple negative breast cancer.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Estimated using the product-limit method of Kaplan and Meier. Failure defined as disease progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Up to 36 months

Secondary Outcomes (3)

• Overall Response

  Up to 36 months

• Clinical Benefit Rate

  Up to 6 months

• Overall Survival (OS)

  Up to 36 months

Study Arms (3)

Arm A (ipatasertib, carboplatin, paclitaxel)

EXPERIMENTAL

Patients receive ipatasertib PO QD on days 1-28. Patients also receive carboplatin IV over 30 minutes and paclitaxel IV over 60 minutes on days 1, 8, and 15 or days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Drug: Ipatasertib; Drug: Paclitaxel; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm B (ipatasertib and carboplatin)

ACTIVE COMPARATOR

Patients receive ipatasertib PO QD on days 1-28. Patients also receive carboplatin IV over 30 minutes on days 1, 8, and 15 or days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Drug: Ipatasertib; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm C (ipatasertib, capecitabine, atezolizumab)

EXPERIMENTAL

Patients receive ipatasertib PO QD on days 1-21, capecitabine PO BID on days 1-7 and 15-21, and atezolizumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Atezolizumab; Drug: Capecitabine; Drug: Ipatasertib; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Arm C (ipatasertib, capecitabine, atezolizumab)

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Arm C (ipatasertib, capecitabine, atezolizumab)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm A (ipatasertib, carboplatin, paclitaxel); Arm B (ipatasertib and carboplatin)

Ipatasertib DRUG

Given PO

Also known as: GDC-0068, RG-7440

Arm A (ipatasertib, carboplatin, paclitaxel); Arm B (ipatasertib and carboplatin); Arm C (ipatasertib, capecitabine, atezolizumab)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm A (ipatasertib, carboplatin, paclitaxel)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (ipatasertib, carboplatin, paclitaxel); Arm B (ipatasertib and carboplatin); Arm C (ipatasertib, capecitabine, atezolizumab)

Questionnaire Administration OTHER

Ancillary studies

Arm A (ipatasertib, carboplatin, paclitaxel); Arm B (ipatasertib and carboplatin); Arm C (ipatasertib, capecitabine, atezolizumab)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form
• Ability to comply with the study protocol, in the investigator's judgment
• Histologically or cytologically confirmed triple negative breast cancer defined by estrogen receptor (ER) or progesterone receptor (PR) =\< 10% by immunohistochemistry (IHC) and HER2 negative defined by current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline
• Disease progression during or following treatment with 0-2 lines of chemotherapy and/or biological targeted therapy in the metastatic setting
• Measurable (Arm C only) or non-measurable (allowed for Arm A or B) but evaluable disease per RECIST version (v)1.1 (Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.)
• Baseline tissue requirement:
• A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 20 x 5 um slides containing unstained, freshly cut, serial sections must be collected along with an associated pathology report prior to study enrollment
• If only 10-19 slides are available, the patient may still be eligible for the study, after principal investigator approval has been obtained
• If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening
• A biopsy may also be performed at screening if a patient's archival tissue test results do not meet eligibility criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Life expectancy \>= 3 months
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (1,500/uL) without granulocyte colony-stimulating factor support (obtained within 14 days prior to initiation of study treatment)
• Platelet count \>= 100 x 10\^9/L (100,000/uL) without transfusion (obtained within 14 days prior to initiation of study treatment)
• Hemoglobin \>= 9 mg/dL (9 mg/dL) (patients may be transfused to meet this criterion) (obtained within 14 days prior to initiation of study treatment)

You may not qualify if:

• Inability to comply with study and follow-up procedures
• \>= grade 3 toxicities from previous treatment, not recovered to =\< grade 2 at study entry
• Prior exposure to PI3K/AKT/mTOR pathway inhibitors including but not limited to everolimus, ipatasertib, gedatolisib or alpelisib etc
• Prior exposure to carboplatin for treatment of metastatic TNBC not allowed; prior treatment of carboplatin as neoadjuvant or adjuvant therapy allowed if last dose of therapy completed \>= 12 months prior to initiation of the current study
• Prior exposure to paclitaxel or nab-paclitaxel for treatment of metastatic TNBC not allowed for carboplatin/paclitaxel arm; prior treatment of paclitaxel or nab-paclitaxel as neoadjuvant or adjuvant therapy allowed if last dose of therapy completed \>= 12 months prior to initiation of the current study
• Prior exposure to capecitabine for treatment of metastatic TNBC not allowed for Arm C; prior treatment of capecitabine as adjuvant therapy allowed if the last dose of therapy completed \>= 12 months prior to initiation of the current study for Arm C
• Prior treatment with immune check point inhibitors for Arm C
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Prior treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment for Arm C
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions for Arm C:
• Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor confirmation has been obtained
• Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
• Active autoimmune disorders requiring steroid dose higher than prednisone 10 mg daily for Arm C
• Active disease or receiving treatment for hepatitis B or C or human immunodeficiency virus (HIV) infection for Arm C
• Receipt of a live, attenuated vaccine within 4 weeks prior to enrollment (start of treatment), during treatment, or within 5 months following the last dose of atezolizumab for Arm C

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (1)

• Yuan Y, Yost SE, Cui Y, Ruel C, Murga M, Tang A, Martinez N, Schmolze D, Waisman J, Patel N, Vora L, Tumyan L, Bozoghlanian M, Stewart D, Frankel PH. Phase I Trial of Ipatasertib Plus Carboplatin, Carboplatin/Paclitaxel, or Capecitabine and Atezolizumab in Metastatic Triple-Negative Breast Cancer. Oncologist. 2023 Jul 5;28(7):e498-e507. doi: 10.1093/oncolo/oyad026.

  PMID: 37023705 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

atezolizumab; Capecitabine; Carboplatin; ipatasertib; Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Joanne Mortimer

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2019
• First Posted: February 26, 2019
• Study Start: March 4, 2019
• Primary Completion: January 21, 2023
• Study Completion: September 19, 2023
• Last Updated: February 20, 2024
• Results First Posted: March 21, 2023

Record last verified: 2024-02

Locations

US (1)