AMTEC IIT: Phase 2 Multiarm Study in TNBC

Stopped early · Phase 2

Conditions studied: Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma

In brief

This phase II study assesses the efficacy of the combination of olaparib with durvalumab, selumetinib, or capivasertib or ceralasertib alone in the treatment of patients with metastatic triple negative breast cancer (TNBC). Olaparib may stop growth of tumor cells by inhibiting some of the enzymes (ADP ribose polymerase \[PARP\]) needed for cell growth. Durvalumab, a monoclonal antibody, inhibits the growth and spread of tumors by stimulating the patient's antitumor immune response. Selumetinib, capivasertib, and ceralasertib are inhibitor drugs that may stop the growth of tumor cells by blocking some of the enzymes (MEK, AKT, ATR) needed for cell growth. Giving olaparib together with durvalumab, selumetinib, or capivasertib or giving ceralasertib alone may provide an effective method to treat patients with metastatic triple negative breast cancer.

Key facts

Study ID

NCT03801369

Run by

Gordon Mills, MD, PhD

People needed

24

Starts

2018-12-12

Expected to finish

2024-12-23

Last updated by the study team

2026-02-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Ability to understand and the willingness to sign a written informed consent document
• Participants are >= 18 years old at time of informed consent.
• Metastatic TNBC, as defined by:
• Estrogen receptor (ER) and progesterone receptor (PR) negative as defined as ER < 10% and PR < 10% by immunohistochemistry according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing
• HER2 non-amplified per ASCO/CAP guidelines, defined as:
• IHC score 0/1+
• IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells; or
• ISH non-amplified with a ratio of HER2 to CEP17 <2.0, and if reported, average HER2 gene copy number < 4 signals/cells
• Participants with or without germline BRCA mutated TNBC are eligible for study participation
• Participants must have at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 that is amenable to biopsy
• Prior therapies for metastatic breast cancer
• Frontline patients who have not received prior systemic therapy for metastatic breast cancer are eligible
• Patients who have received =< 2 prior chemotherapy regimens for metastatic breast cancer are eligible
• Participants must have fully recovered from the acute toxic effects of all prior treatment to grade 1 or less, except alopecia which is allowed
• Participants must have a life expectancy >= 16 weeks
• Participant must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Participant must consent to undergo a pre-treatment screening biopsy for enrollment and subsequent biomarker analyses
• Participants must consent to undergo one mandatory on-study tumor biopsy following a 2-week induction treatment of olaparib. A second on-study biopsy at time of disease progression is optional, but not mandatory
• Participants must not have received previous treatment with PARP inhibitors, including olaparib
• Hemoglobin >= 10.0 g/dL (measured within 28 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 1.5 x 10\^9/L (measured within 28 days prior to administration of study treatment)
• Platelet count >= 100 x 10\^9/L (measured within 28 days prior to administration of study treatment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be =< 5 x ULN (measured within 28 days prior to administration of study treatment)
• Participants must have creatinine clearance estimated of >= 51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test (measured within 28 days prior to administration of study treatment)

You may not qualify if…

• Any concurrent anticancer treatment
• Individuals in the follow-up phase of a prior investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent or device
• Concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) is allowed
• Participant's with tumors showing androgen receptor (AR) >= 80% by immunohistochemistry are excluded
• Other malignancy unless curatively treated with no evidence of disease for >= 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma. Participants with a personal history of treated early stage breast cancer whose natural history or treatment does not have the potential to interfere with the safety or efficacy endpoints of the trial, per investigator assessment, are eligible
• Participants with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
• Participant received prior anticancer therapy such as targeted therapies, or systemic chemotherapy or radiation (except for palliative reasons) within the past 3 weeks, or 5 half-lives, whichever is shorter, prior to first day of treatment
• Participants with known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Patients with brain metastases may participate provided they do not have symptomatic uncontrolled disease. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. (note: a scan to confirm the absence of brain metastases is not required)
• Patients with spinal cord compression are not eligible unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• Patients with carcinomatous meningitis are not eligible
• Concomitant use of known strong CYP3A inhibitors (e.g., ketoconazole, posaconazole), or strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting study intervention treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
• Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
• Patients that are immunocompromised, including those with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness are not eligible for participation
• Note: HIV-infected participants on effective anti-retroviral therapy with undetectable viral load for >= 6 months are eligible for this trial provided that there is minimal interactions or overlapping toxicity of the antiretroviral therapy with their study intervention. Refer to drug-specific exclusion criteria for additional considerations
• Patients with known active hepatitis (i.e. hepatitis B or C). Refer to drug-specific exclusion criteria for additional considerations
• Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result
• Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. Those with a positive HCV PCR will be excluded
• Participants unable to swallow orally administered medication and participants with gastrointestinal disorders likely to interfere with absorption of the study medication
• Participants with visceral crisis defined as severe organ dysfunction as assessed by signs and symptoms, laboratory studies, and rapid progression of disease
• Active infection requiring systemic antibiotic therapy. Participants requiring systemic antibiotics for infection must have completed therapy before treatment is initiated
• Participants considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric illness/social situation that prohibits obtaining informed consent
• Resting electrocardiography (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fridericia's correction formula (QTcF) prolongation > 500 ms, electrolyte disturbances, etc.), or participants with congenital long QT syndrome

Where it is running

• OHSU Knight Cancer Institute — Portland, Oregon, United States

Full record on ClinicalTrials.gov

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