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Metastatic Breast CancerPhase 1IPATHERNCT04253561

Ipatasertib + Pertuzumab +Trastuzumab in Advanced HER2+ PI3KCA-mutant Breast Cancer Patients

A Phase 1 study testing Ipatasertib, Trastuzumab and Pertuzumab in people with Metastatic Breast Cancer, run by SOLTI Breast Cancer Research Group at 10 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open label, single arm, multicenter, phase Ib study to evaluate the safety and clinical activity of the combination of ipatasertib, trastuzumab and pertuzumab in patients with unresectable locally advanced or metastatic HER2-positive breast cancer with tumors harboring PIK3CA mutations, candidates to… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Ipatasertib, Trastuzumab and Pertuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
10 sitesSpain
Study dates
25 Feb 2020to 17 Jun 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written and signed informed consent for all study procedures according to local regulatory requirements prior to beginning of specific protocol procedures.
  • Female (pre- or postmenopausal) or male patients.
  • Age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Confirmed HER2-positive invasive breast cancer by central determination defined by American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) clinical practice guidelines. (Wolff el al. Arch Pathol Lab Med-Vol 142, November 2018;).
  • Known hormone receptor status, as assessed locally, defined by ASCO/CAP clinical practice guidelines. ER/PR positivity is defined as the presence of ≥ 1% of tumor cells with nuclear staining (Hammond et al. JCO 2010).
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  • Histologically confirmed, locally advanced or metastatic adenocarcinoma of the breast.
  • Patients with unresectable locally advanced disease must have recurrent or progressive disease, which must not be amenable to resection with curative intent. Patients with available standard curative options are not eligible.
  • For patients with bilateral breast cancer, HER2-positivity must be demonstrated in both locations or in a metastatic biopsy.
  • Patient must be a candidate to receive maintenance HP after first line treatment for metastatic disease with at least 4 cycles of taxane plus HP.
  • Prior taxane must have been discontinued for a reason other than progressive disease.
  • Patients may or may not have received neo/adjuvant therapy but must have a disease-free interval from completion of anti-HER2 therapy to metastatic diagnosis ≥6 months.
  • PIK3CA mutation identified and confirmed in tumor tissue or plasma ctDNA by central determination.
  • Start of treatment with ipatasertib plus HP no later than 9 weeks after last dose of taxane plus HP (i.e., maximum of 2 HP administrations with no taxane).
  • Willingness and ability to provide archived formalin fixed paraffin embedded (FFPE) tissue block.
  • Measurable or non-measurable (but evaluable) disease, as per RECIST 1.1 criteria.
  • No baseline diarrhea or diarrhea grade ≤1 within the last 28 days.
  • Adequate hematologic and organ function within 14 days before the first study treatment on Day 1 of Cycle 1, defined by the following:
  • Neutrophils (ANC ≥1500/μL)
  • Hemoglobin ≥9 g/dL (with no need for transfusions in the last 14 days).
  • Platelet count ≥75,000/μL
  • Serum albumin ≥3 g/dL
  • Total bilirubin ≤1.5x the upper limit of normal (ULN), with the exception: patients with known Gilbert syndrome who have serum bilirubin ≤3x ULN.
  • AST and ALT ≤2.5x ULN, with the following exception: patients with documented liver or bone metastases who may have AST and ALT ≤5x ULN.
  • ALP ≤2x ULN, with the following exceptions:
  • Patients with known liver involvement who may have ALP ≤5x ULN.
  • Patients with known bone involvement who may have ALP ≤7x ULN.
  • PTT (or aPTT) and INR ≤1.5x ULN (except for patients receiving anticoagulation therapy).
  • Patients receiving heparin treatment should have a PTT (or aPTT) between 1.5 and 2.5x ULN.
  • Patients receiving coumarin derivatives should have an INR between 2.0 and 3.0 assessed in two consecutive measurements 1 to 4 days apart.
  • Serum creatinine <1.5x ULN or creatinine clearance ≥50 mL/min based on Cockcroft-Gault glomerular filtration rate estimation:
  • (140 - age) x (weight in Kg) x 0.85 (if female)/72 x (serum creatinine in mg/dL)
  • Fasting total serum glucose ≤150mg/dL and glycosylated hemoglobin (HbA1C) ≤7.5%
  • Life expectancy of at least 6 months.
  • Baseline left ventricular ejection fraction (LVEF) ≥50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan.
  • Negative β-HCG pregnancy test (serum) for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after the menopause. All subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control from 2 weeks before administration of the first dose of investigational product until 28 days after the last dose of investigational product.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Who cannot join

  • Last dose of taxane plus HP given more than 9 weeks prior to C1D1.
  • Prior malignancy within 3 years prior to randomization, except curatively treated non-melanoma skin, carcinoma in situ of the cervix or Stage I uterine cancer.
  • Brain metastases that have not been treated previously, are progressive, or require any type of therapy (e.g., radiation, surgery, or steroids) to control symptoms within 30 days prior to the first study treatment dose.
  • Radiotherapy for metastatic sites of disease outside of the brain performed within 14 days prior to study enrollment and/or radiation of >30% of marrow-bearing bone.
  • Symptomatic hypercalcemia requiring use of bisphosphonate or RANKL inhibitors therapy within 21 days prior to the first study treatment. Patients who receive bisphosphonate therapy specifically to prevent skeletal events are eligible if they have been initiated prior to the treatment to study.
  • Cardiopulmonary dysfunction as defined by:
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  • Inadequately controlled angina or serious cardiac arrhythmia not controlled by adequate medication.
  • Inadequate LVEF at baseline, as defined as LVEF <50% by either ECHO or MUGA scan.
  • History of symptomatic congestive heart failure (CHF): Grade ≥3 per NCI CTCAE version 4.03 or Class ≥II New York Health Association (NYHA) criteria.
  • History of a decrease in LVEF to <40% or symptomatic CHF with prior trastuzumab or HP treatment.
  • History of myocardial infarction within 6 months prior to randomization.
  • Current dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy.
  • Congenital long QT syndrome or screening QT interval corrected using Fridericia's formula (QTcF) > 480 milliseconds.
  • Concurrent, serious, uncontrolled infections or current known infection with HIV (testing is not mandatory).
  • History of intolerance, including Grade 3-4 infusion reaction or hypersensitivity, to trastuzumab or pertuzumab.
  • Known hypersensitivity to any of the study drugs, including excipients.
  • Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis (e.g., positive for hepatitis B surface antigen [HBsAg] or hepatitis C virus [HCV] antibody at screening), current drug or alcohol abuse, or cirrhosis.
  • Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [HBcAg] antibody test) are eligible.
  • Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
  • History of Type I or Type II diabetes mellitus requiring insulin. Patients who are on stable dose of oral diabetes medication > 2 weeks prior to initiation of study treatment are eligible for enrollment.
  • Grade ≥2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.
  • History of or active inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis).
  • Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (Pneumocystis pneumonia or Cytomegalovirus pneumonia).
  • Need for chronic corticosteroid therapy of >10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids for a chronic disease.
  • Uncontrolled pleural effusion, pericardial effusion, or ascites. Patients with indwelling catheters (e.g., PleurX®) are allowed.
  • Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug.
  • Prior treatment with an AKT inhibitor. Prior PI3K or mTOR inhibitors are allowed.
  • Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary or metabolic disease; wound healing disorders; ulcers; bone fractures).
  • Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy.
  • Major surgical procedure or significant traumatic injury within 28 days prior to enrollment.
  • Assessment by the investigator to be unable or unwilling to comply with the requirements of the protocol.
  • History of significant comorbidities that, in the judgment of the investigator, may interfere with the conduction of the study, the evaluation of response, or with informed consent.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Spain10 sites

  • ICO Badalona

    Badalona, Barcelona

  • Hospital Universitario del Vall d' Hebron

    Barcelona, Barcelona

  • H.Univ. Arnau de Vilanova de Lleida

    Lleida, Lleida

  • Centro Integral Oncológico Clara Campal (CIOCC)

    Madrid, Madrid

  • Hospital Universitario Doce de Octubre

    Madrid, Madrid

  • MD Anderson

    Madrid, Madrid

  • Comp. Hosp.Univ. Santiago (Chus)

    Santiago de Compostela, La Coruña

  • Hospital Universitario Virgen del Rocio

    Seville, Sevilla

  • Hospital Virgen de Macarena

    Seville, Sevilla

  • Fundación Instituto Valenciano de Oncología

    Valencia, Valencia

Other trials in Spain

About this study

Official title: A Phase Ib Study of Ipatasertib, an AKT Inhibitor, in Combination With Pertuzumab Plus Trastuzumab in Patients With PI3KCA-mutant, HER2-positive Locally Advanced or Metastatic Breast Cancer

This is an open label, single arm, multicenter, phase Ib study to evaluate the safety and clinical activity of the combination of ipatasertib, trastuzumab and pertuzumab in patients with unresectable locally advanced or metastatic HER2-positive breast cancer with tumors harboring PIK3CA mutations, candidates to receive maintenance HP after first line treatment for metastatic disease with a taxane plus HP

Read the detailed description

The main objective of the study is to assess whether the combination of ipatasertib and HP (+/- ET) is tolerable, especially in terms of the incidence and severity of diarrhea. For this purpose, up to a total of 25 patients will be enrolled in a staggered manner and evaluated.

A 3-cohort, descending doses (400, 300, 200 mg) design will serve to establish the Maximun Toleraded Dose (MTD) and Recommended Phase 2 Dose (RP2D) of ipatasertib in combination with HP.

The study will initially include 6 patients that will receive ipatasertib plus HP at Dose Level 1.

If ≤1 DLTs are observed, this dose will be deemed safe, and the trial will enroll at least additional 19 patients to further assess safety and preliminary efficacy of the combination.

If ≥2 DLT occurs in the first 6 patients, a decision will be made of whether expand Dose Level 1 to 10 additional patients or to de-escalate ipatasertib to the next lower dose level. In the case of de-escalation, the same rules will apply for enrollment and expansion of Dose level -1. The minimum ipatasertib dose explored will be Dose level -2.

Dose reductions of pertuzumab and trastuzumab will not be allowed.

If all inclusion criteria and no exclusion criteria are met, patients will be enrolled in the trial and will start treatment with oral (PO) ipatasertib once a day (QD) D1-21 in 28-days cycles, together with pertuzumab 420 mg intravenous (IV) every 21 days (Q21d) and trastuzumab 600 mg subcutaneous (SC) Q21d.

Patients with hormone receptor positive (HR+) tumors (defined as ER and/or PgR expression in >1% of tumor cells) will also receive endocrine therapy either an Aromatase Inhibitor (AI), tamoxifen or fulvestrant +/- Luteinizing Hormone-Releasing Hormone (LHRH) analogues, according to Investigator's decision.

Patients will also start loperamide (2 mg twice a day [BID] or 4 mg QD) as prophylaxis for diarrhea in the first cycle

Being tested
Ipatasertib, Trastuzumab, Pertuzumab
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpatasertibDrug

    Also called GDC-0068

    Ipatasertib will be administered orally once a day, beginning on Cycle 1, Day 1 through Day 21 of each 28-day cycle.

  • TrastuzumabDrug

    Also called Herceptin

    600 mg every 3 weeks

  • PertuzumabDrug

    Also called Perjecta

    420 mg every 3 weeks

Study groups in NCT04253561
Study groupRoleWhat they receive
Ipatasertib + Trastuzumab + PertuzumabExperimentalIpatasertib will be given from Day 1 to Day 21 in every 28-day cycles. The starting dose is 400 mg orally (PO) QD and may be decreased to 300 mg QD and further to 200 mg QD (dose levels 1, - 1 and -2, respectively). Pertuzumab will be given IV every 21 days at the dose of 420 mg. Trastuzumab will be given SC every 21 days at the dose of 600mg. Intravenous (IV) Trastuzumab
Receives: Drug: Ipatasertib; Drug: Trastuzumab; Drug: Pertuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To define the Recommended Phase 2 Dose (RP2D) of ipatasertib when used in combination with HP (+/- ET)

    The RP2D will be the dose level of ipatasertib at which no more than 1 subject of the study experiences a Dose Limiting Toxicity (DLT) defined by the protocol study.

    Measured: From baseline to the end of cycle 1, up to 28 days

Secondary outcomes (6)

  1. To evaluate the safety of the combination of ipatasertib with HP (+/- endocrine therapy [ET]).

    Number of patients with adverse events (AEs) and severe adverse events (SAEs) as per NCI CTCAE v4.03 of the combination of ipatasertib plus HP (+/- ET), with a special emphasis on the onset and severity of diarrhea.

    Measured: Toxicities will be assessed during the whole treatment period (from baseline until lasts until 6 months after a patients' final treatment which is defined as the end of the Treatment Phase of the study).

  2. To evaluate the tolerability of the combination of ipatasertib with HP (+/- endocrine therapy [ET]).

    Quantification of dose interruptions, reductions and dose intensity

    Measured: Toxicities will be assessed during the whole treatment period (from baseline until lasts until 6 months after a patients' final treatment which is defined as the end of the Treatment Phase of the study).

  3. Objective Response Rate (ORR) of the combination of ipatasertib with HP (+/- ET) as maintenance therapy after first line treatment for HER2-positive metastatic BC with a taxane plus HP.

    Proportion of patients who have a complete response (CR) or partial response (PR), as determined by the investigator through use of RECIST v1.1.

    Measured: From date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal or study termination, whichever came first, assessed up to 20 months .

  4. Duration of Response (DoR) to the combination of ipatasertib with HP (+/- ET) as maintenance therapy after first line treatment for HER2-positive metastatic BC with a taxane plus HP.

    Time from the first occurrence of a documented Objective Response (OR) to disease progression, according to RECIST v1.1, or death from any cause, whichever occurs first.

    Measured: From date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal or study termination, whichever came first, assessed up to 20 months .

  5. Clinical Benefit Rate (CBR) of the combination of ipatasertib with HP (+/- ET) as maintenance therapy after first line treatment for HER2-positive metastatic BC with a taxane plus HP.

    Percentage of patients achieving confirmed CR, PR or stable disease (SD) for at least 24 weeks after the beginning of the study treatment by RECIST v1.1.

    Measured: From date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal or study termination, whichever came first, assessed up to 20 months .

  6. Progression-free survival (PFS) to the combination of ipatasertib with HP (+/- ET) as maintenance therapy after first line treatment for HER2-positive metastatic BC with a taxane plus HP.

    Time from the commencement of study treatment (Day 1) to the occurrence of PD, as determined by the investigator via RECIST v1.1, or death from any cause, whichever occurs first.

    Measured: From date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal or study termination, whichever came first, assessed up to 20 months .

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2020
  2. Study start25 Feb 2020
  3. Primary completion5 Dec 2021
  4. Study completion17 Jun 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04253561
Sponsor's protocol ID
SOLTI-1507
Other IDs
2019-001526-94, 2019
Acronym
IPATHER
Status last verified
Mar 2026
First submitted
17 Jan 2020
Last updated
16 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ipatasertib, Trastuzumab and Pertuzumab in people with Metastatic Breast Cancer, run by SOLTI Breast Cancer Research Group at 10 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To define the Recommended Phase 2 Dose (RP2D) of ipatasertib when used in combination with HP (+/- ET) (time frame: From baseline to the end of cycle 1, up to 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04253561.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2026.

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