Ipatasertib Plus Non-Taxane Chemotherapy for Advanced or Metastatic Triple-Negative Breast Cancer

NCT04464174 | Completed Phase 2

• 2 other identifiers: MedOPP2532018-004648-44
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 14

Brief Summary

This is a multicenter, open-label, non-comparative, three-arm, phase IIa trial of Ipatasertib (GDC-0068) in combination with non-taxane chemotherapy agents for taxane-pretreated unresectable locally advanced or metastatic triple-negative breast cancer patients

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine; as incidence of Adverse Events as assessed by the investigator, with severity determined through the use of NCI-CTCAE v.4.03

  To evaluate the safety and tolerability of ipatasertib (400 mg) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine

  From baseline up to 15 months

Secondary Outcomes (7)

• Progression Free Survival (PFS)

  From baseline up to 15 months

• Time to response (TTR)

  From baseline up to 15 months

• Objective response rate (ORR)

  From baseline up to 15 months

• Duration of Response (DoR)

  From baseline up to 15 months

• Clinical Benefit Rate (CBR)

  From baseline up to 15 months

Study Arms (3)

Ipatasertib plus capecitabine

EXPERIMENTAL

Arm A: Ipatasertib (GDC-0068) 400 milligrams (mg) tablets administered orally once a day (noon) on Days 1-14 of each 21-day cycle plus capecitabine 1000 mg/m2 tablets orally twice a day (morning and evening; equivalent to 2000 mg/m2 total daily dose), for 14 days (followed by a 7-day rest period) every 21-day cycle.

Drug: Ipatasertib; Drug: Capecitabine

Ipatasertib plus Eribulin

EXPERIMENTAL

Arm B: Ipatasertib (GDC-0068) 400 mg tablets administered orally once a day on Days 1-14 of each 21-day cycle plus eribulin 1.23 mg/m2 (equivalent to eribulin mesylate at 1.4 mg/m2) administered intravenously over 2 to 5 minutes on Days 1 and 8 of every 21-day cycle.

Drug: Ipatasertib; Drug: Eribulin

Ipatasertib plus carboplatin plus gemcitabine

EXPERIMENTAL

Arm C: Ipatasertib (GDC-0068) 400 mg tablets administered orally once a day on Days 1-14 of each 21-day cycle plus carboplatin AUC5 on Day 1 administered intravenously plus gemcitabine 1000 mg/m2 administered intravenously over 30 minutes on Days 1 and 8, every 21-day cycle.

Drug: Ipatasertib; Drug: Carboplatin; Drug: Gemcitabine

Interventions

Ipatasertib DRUG

Ipatasertib administered orally (400 mg) once a day, from day 1 to day 14, and rest from day 15 to day 21 of every 21-day cycle

Also known as: GDC-0068

Ipatasertib plus Eribulin; Ipatasertib plus capecitabine; Ipatasertib plus carboplatin plus gemcitabine

Capecitabine DRUG

Capecitabine administered orally (1000 mg/m2) twice a day, from day 1 to day 14, and rest from day 15 to day 21 of every 21-day cycle

Also known as: Xeloda

Ipatasertib plus capecitabine

Eribulin DRUG

Eribulin 1.23 mg/m2 administered intravenously Days 1 and 8 of every 21-day cycle

Also known as: Halaven

Ipatasertib plus Eribulin

Carboplatin DRUG

Carboplatin AUC5 administered intravenously day 1 of every 21-day cycle

Also known as: Paraplatin

Ipatasertib plus carboplatin plus gemcitabine

Gemcitabine DRUG

Gemcitabine administered intravenously (1000 mg/m2) at days 1 and 8 of every 21-day cycle

Also known as: Gemzar

Ipatasertib plus carboplatin plus gemcitabine

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form (ICF) prior to participation in any study-related activities.
• Female patients ≥ 18 years at the time of signing ICF.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy of ≥ 12 weeks.
• Histologically confirmed Triple Negative Breast Cancer (TNBC) per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria based on local testing on the most recent analyzed biopsy. Triple-negative is defined as \<1% expression for estrogen receptor (ER) and progesterone receptor (PgR) and negative for Human Epidermal Growth Factor Receptor 2 (HER2) (0-1+ by immunohistochemistry (IHC) or 2+ and negative by in situ hybridization \[ISH) test\].
• Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
• Measurable or evaluable disease as per RECIST v.1.1. Patients with only bone lesions are also eligible.
• Refractory to or relapsed after one or two prior standard of care chemotherapy regimens for unresectable locally advanced or metastatic breast cancer (MBC). Earlier adjuvant or neoadjuvant therapy for more limited disease will be considered as one of the required prior regimens if the development of unresectable locally advanced or metastatic disease occurred within a 12-month period of time after completion of chemotherapy.
• Note: Exclusive tumor marker elevation will not be considered sufficient for diagnosis of disease progression.
• Prior therapy must have included a taxane in any combination or order and either in the early, locally advanced, or metastatic setting. Note: Exclusive prior taxane-based therapy as adjuvant or neoadjuvant treatment is also allowed if the patient had a disease-free interval of less than 12 months after completing this treatment.
• Eligible for one of the chemotherapy options (eribulin, capecitabine, carboplatin plus gemcitabine) as per local investigator assessment and slots availability. Patients treated with (neo)adjuvant platinum salts or capecitabine and who have relapsed more than one year after the last dose of either treatment may be allowed to be included in the treatment arm based on ipatasertib (GDC-0068) in combination with carboplatin plus gemcitabine and capecitabine, respectively.
• Previous treatment with androgen receptor antagonists, poly ADP-ribose Polymerase (PARP) inhibitors, and immunotherapy is allowed. Those patients who have previously received a PARP inhibitor will not be included in the carboplatin and gemcitabine arm unless PARP inhibitors were used in the early breast cancer setting and the period between the end of PARP inhibitor-based regimen and onset of metastatic disease is at least of 12 months.
• Resolution of all acute toxic effects of prior anti-cancer therapy to grade inferior or equal to 1 as determined by the NCI-CTCAE v.5.0 (except for alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
• Adequate hematologic and organ function within 14 days before the first study treatment on Day 1 of Cycle 1, defined by the following:
• Hematological: White blood cell (WBC) count \> 3.0 x 109/L, absolute neutrophil count (ANC) \> 1.5 x 109/L, platelet count \> 100.0 x109/L, and hemoglobin \> 9.0 g/dL.

You may not qualify if:

• Inability to comply with study and follow-up procedures.
• Previous treatment with PI3K, mTOR, or AKT inhibitors.
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (e.g., radiotherapy, stereotactic surgery), are clinically stable, and off anticonvulsants and steroids for at least two weeks before first dose of study treatment.
• Radiotherapy or limited-field palliative radiotherapy within seven days prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously irradiated.
• Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 28 days of start of study drug, or patients who have not recovered from the side effects of any major surgery.
• Grade ≥ 2 peripheral neuropathy.
• Grade ≥ 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.
• History of type I or type II diabetes mellitus either requiring insulin or with a baseline fasting glucose \> 150 mg/dL (8.3 mmol/L) or high hemoglobin A1c (HbA1c) as defined as \> 7%. Patients who are on a stable dose of oral diabetes medication during at least weeks prior to initiation of study treatment are eligible for enrolment.
• Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia).
• History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills.
• History of or active inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis).
• Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances.
• Patients have a concurrent malignancy or malignancy within five years of study enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.
• Current known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antibody \[HBsAg\] test and a positive hepatitis B core antibody \[HBcAb\] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• Active uncontrolled infection at the time of enrollment.

Sponsors & Collaborators

• MedSIR: lead
• Hoffmann-La Roche: collaborator

Study Sites (14)

Champalimaud Clinical Centre - Champalimaud Foundation

Lisbon, 1400-038, Portugal

Location

Instituto Português de Oncologia do Porto FG, EPE (IPO-Porto)

Porto, 4200-072, Portugal

Location

Hospital Provincial de Castellón

Castellon, Castellón, 12002, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitari Dexeus

Barcelona, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Universitari Arnau de Vilanova

Lleida, 25198, Spain

Location

Hospital Quiron San Camilo- Ruber Juan Bravo

Madrid, 28006, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Arnau de Vilanova

Valencia, 46015, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Related Publications (1)

• Lopez-Miranda E, Perez-Garcia JM, Gion M, Ribelles N, Cortez-Castedo P, Alonso-Romero JL, Garcia MM, Gonzalez-Santiago S, Bermejo B, Morales S, Caranana V, Garrigos L, Fernandez-Pinto M, Garcia-Vicente S, Garcia-Sanz A, Mena-Molina A, Boix O, Alcala-Lopez D, Llombart-Cussac A, Cortes J. Ipatasertib combined with non-taxane chemotherapy for patients with previously treated advanced triple-negative breast cancer: the PATHFINDER phase IIa trial. Breast Cancer Res. 2025 Aug 6;27(1):141. doi: 10.1186/s13058-025-02089-4.

  PMID: 40770648 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

ipatasertib; Capecitabine; eribulin; Carboplatin; Gemcitabine

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

Study Officials

• Antonio Llombart, MD

  MedSIR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 9, 2020
• Study Start: October 8, 2020
• Primary Completion: November 10, 2023
• Study Completion: November 10, 2023
• Last Updated: July 26, 2024

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (12); PT (2)