Inhibition of AKT in combination with antibodies targeting the protein HER2 in patients with advanced or metastatic breast cancer and with a mutation in the gene PIK3CA

Phase 1

• Conditions: Patients with PIK3CA-mutant, HER2-positive locally advanced or metastatic breast cancer, candidates to receive maintenance therapy with trastuzumab plus pertuzumab (HP) after first line treatment for metastatic disease with a taxane or vinorelbine plus HP.; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-508826-92-00
• Lead Sponsor: Solti Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-06-12
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

Written and signed informed consent for all study procedures according to local regulatory requirements prior to beginning of specific protocol procedures., 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. If prior approval has been granted by the Sponsor, centrally confirmed PIK3CA mutation result from a current or previous study identified by the sponsor can be used to determine eligibility for this study., Start of treatment with ipatasertib plus HP no later than 9 weeks after last dose of taxane or vinorelbine plus HP (i.e., maximum of 2 HP administrations with no taxane or vinorelbine)., Willingness and ability to provide archived formalin fixed paraffin embedded (FFPE) tissue block., 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: a. Neutrophils (ANC =1500/µL) b. Hemoglobin =9 g/dL (with no need for transfusions in the last 14 days). c. Platelet count =75,000/µL d. Serum albumin =3 g/dL e. Total bilirubin =1.5x the upper limit of normal (ULN), with the exception: patients with known Gilbert syndrome who have serum bilirubin =3x ULN. f. 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. g. 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. h.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. i. 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) j. 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 ß-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., 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 the current Am

Exclusion Criteria

Last dose of taxane or vinorelbine plus HP given more than 9 weeks prior to C1D1., 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., 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., 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, 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified