Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Condition: Advanced Lymphoma; Advanced Malignant Solid Neoplasm; Hematopoietic and Lymphoid Cell Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma
MeSH terms: Lymphoma; Neoplasms; Multiple Myeloma
Intervention: Capivasertib
Intervention description: Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II MATCH treatment trial identifies the effects of AZD5363 in patients whose
      cancer has a genetic change called AKT mutation. AZD5363 may block AKT, which is a protein
      needed for cancer cell growth. Researchers hope to learn if AZD5363 will shrink this type of
      cancer or stop its growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have met applicable eligibility criteria in the Master MATCH Protocol
             prior to registration to treatment subprotocol

          -  Patients must have an AKT mutation as determined via the MATCH Master Protocol

          -  Patients with hormone receptor positive, defined as estrogen receptor and/or
             progesterone receptor > 1% by immunohistochemistry, AND HER2 negative unresectable
             breast cancer, with no overexpression by immunohistochemistry (IHC) or amplification
             by in-situ hybridization, are allowed to continue fulvestrant or an aromatase
             inhibitor (anastrozole, letrozole, exemestane) with AZD5363 if patient just progressed
             on this anti-estrogen therapy. Gonadotrophin releasing hormone (GnRH) agonists (such
             as leuprolide or goserelin) are allowed. For instance, if the last treatment was
             letrozole plus goserelin, the patient is allowed to continue the letrozole plus
             goserelin with AZD5363

               -  NOTE: Selective estrogen receptor modulators (SERMs), such as tamoxifen or
                  toremifene, are not allowed, given concerns about CYPD26 and CYP3A4 metabolism,
                  respectively

          -  Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment
             assignment and must have no clinically important abnormalities in rhythm, conduction
             or morphology of resting ECG (e.g. complete left bundle branch block, third degree
             heart block)

          -  Patients with diabetes or risk for hyperglycemia are eligible. Patients with diabetes
             mellitus may enter the study unless any of the following exclusion criteria are
             fulfilled:

               -  Baseline fasting glucose value of > 8.9 mmol/L or 160 mg/dL (fasting is defined
                  as no calorific intake for at least 8 hours)

               -  Insulin required for routine diabetic management and control

               -  More than two oral hypoglycemic medications required for routine diabetic
                  management and control

        Exclusion Criteria:

          -  Patients must not have known hypersensitivity to AZD5363 or compounds of similar
             chemical or biologic composition

          -  Patients with known KRAS, NRAS, HRAS, or BRAF mutations are not eligible for this
             protocol, as these mutations may lead to limited response due to resistance

          -  Patients may not have received treatment with another inhibitor of PI3K, AKT or mTOR
             in the neoadjuvant, adjuvant or metastatic setting with the exception of FDA approved
             rapalogs. Patients with metastatic cancer, who received PI3K/AKT/mTOR inhibitors on
             short preoperative window trials (treatment for 4 weeks or less) will be eligible if
             the treatment was over 6 months prior to registration

          -  Patients may not have received strong inhibitors or potent inducers or substrates of
             CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment
             (3 weeks for St John's Wort)