Clinical trial NCT02078648 (phase 1/phase 2, status: completed)
Conditions: adult brain glioblastoma, glioblastoma multiforme
ICD codes: L51.0, L51.8, L51.9
Drugs: bevacizumab
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Eligibility criteria:

        Inclusion Criteria:

          -  18 years of age or older.

          -  Histologically confirmed GBM or World Health Organization (WHO) Grade IV variants
             (gliosarcoma, glioblastoma with oligodendroglial features, or giant cell
             glioblastoma).

          -  Uneqivocal evidence of a first tumor recurrence or progression on the initial
             treatment regimen (prior to enrollment on this study), consisting of surgical
             intervention (biopsy and/or resection), radiation, and temozolomide chemotherapy, as
             assessed by MRI or CT scan of the brain with or without contrast within 14 days prior
             to the start of SL-701. If receiving corticosteroids, the dose must be stable or
             decreasing for at least 5 days prior to the scan. Patients unable to undergo MRI
             because of non-compatible devices can be enrolled, provided CT scans are obtained and
             are of sufficient quality. For each patient, the same imaging technique should be
             performed throughout the study, for purposes of assessing tumor response or PD.

          -  For patients who have undergone resection of recurrent or progressive tumor prior to
             study enrollment, the following conditions must apply:

               -  Recovery from the effects of surgery.

               -  Residual disease following resection of recurrent tumor is not mandated for
                  eligibility into the study. To best assess the extent of residual disease
                  post-operatively, an MRI should be performed:

                    -  No later than 96 hours (h) in the immediate post-operative period; or

                    -  At least 4 weeks post-craniotomy (7 days for stereotactic biopsy), within 14
                       days prior to the start of SL-701, and on a corticosteroid dosage that has
                       been stable or decreasing for at least 5 days.

          -  Patients who have not had resection of recurrent or progressive disease must have
             measurable disease.

          -  At least 56 of the approximately 76 patients treated must have measurable disease,
             defined as at least one, contrast-enhancing lesion measuring at least 1 cm in 2 planes
             (axial, coronal, or sagittal).

          -  No evidence of hemorrhage on the baseline MRI or CT scan other than those that are
             Grade ≤ 1 and either post-operative or stable on at least two consecutive scans.

          -  Recovery from prior therapy toxicity, defined as resolution of all treatment-related
             adverse events (AEs) to Grade ≤ 1 or pre-treatment baseline (except alopecia and
             lymphopenia).

          -  At least 12 weeks from prior radiotherapy to the start of SL-701 unless there is new
             enhancement outside of the radiation field or unequivocal histopathologic evidence of
             recurrent tumor.

          -  No chemotherapy or investigational agent for at least 3 weeks prior to the start of
             SL-701, with at least 6 weeks of elapsed time from last dose of nitrosoureas.

          -  Human leukocyte antigen (HLA)-A2 positive.

          -  A tumor tissue sample is provided for immunohistochemical analysis of relevant
             antigens, immune markers and potential prognostic factors. Preferably a paraffin block
             or 10-12 unstained slides will be submitted prior to study entry. Patients for whom
             tumor samples are unavailable or inadequate are permitted to participate in the study;
             however, the absence of available/adequate tumor specimen must be documented.

          -  Karnofsky performance status (KPS) score ≥ 70%.

          -  Adequate organ function, including the following:

               -  Absolute neutrophil count (ANC) ≥ 1,000/μL, platelets ≥ 100,000/μL.

               -  Serum creatinine < 1.5 × the upper limit of normal (ULN).

               -  Bilirubin < 1.5 × ULN.

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN.

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 3 days prior to the start of SL-701 treatment.

          -  Female patients of childbearing potential and sexually active male patients must agree
             to use an acceptable form of contraception for heterosexual activity (ie, oral
             contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted
             contraceptives, tubal ligation, or vasectomy of their sexual partner(s) for > 40 days
             before Screening, during the study, and for 60 days after the last dose of study drug.
             Men should not donate semen during the study and for 60 days after the last dose of
             study drug.

          -  Female patients without childbearing potential (spontaneous amenorrhea for > 12 months
             or surgically sterilized by tubal ligation, hysterectomy, or bilateral oophorectomy >
             6 months before Screening) are eligible for inclusion without contraceptive use
             restriction.

          -  Able and willing to comply with protocol requirements, in the opinion of the
             investigator.

          -  A written and voluntarily signed informed consent must be obtained from the patient or
             legally authorized representative, in accordance with local regulations, before the
             initiation of any study related procedures. The patient or legally authorized
             representative must be able to read and understand the informed consent form (ICF).

        Exclusion Criteria:

          -  Prior cancer chemotherapy, bevacizumab (or other vascular endothelial growth factor
             [VEGF]/VEGF receptor [VEGFR]-directed agent), or an investigational agent for
             recurrent/progressive GBM or prior bevacizumab as part of initial therapy (prior
             chemotherapy or investigational agents are permitted as part of initial therapy;
             VEGF/VEGFR-directed agents are not permitted).

          -  Contrast-enhancing tumor that is any of the following:

               -  Multi-focal (defined as two separate areas of contrast enhancement measuring at
                  least 1 cm in 2 planes that are not contiguous on either fluid-attenuated
                  inversion recovery (FLAIR) or T2 sequences);

               -  Associated with either diffuse subependymal or leptomeningeal dissemination; or

               -  ≥ 4 cm in any dimension.

          -  Requirement of systemic corticosteroid therapy > 4 mg/day of dexamethasone or
             equivalent or requirement of increasing dose of systemic corticosteroids during the 7
             days prior to the start of SL-701 treatment.

          -  Surgical resection or major surgical procedure within 4 weeks prior to the start of
             SL-701, or stereotactic biopsy within 7 days prior to the start of SL-701.

          -  Radiation therapy, local therapy (except for surgical re-resection), or systemic
             therapy following first recurrence/progressive disease. Excluded local therapies
             include stereotactic radiation boost, implantation of carmustine biodegradable wafers
             (Gliadel), intratumoral or convection-enhanced delivery administered agents, etc.

          -  Active infection requiring intravenous antibiotics.

          -  History of cancer (other than GBM) within the past 2 years that has metastatic or
             local recurrence potential and could negatively impact survival and/or potentially
             confound tumor response assessments within this study.

          -  Clinically significant cardiovascular disease (eg, uncontrolled or any New York Heart
             Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of
             myocardial infarction or stroke within 6 months of study entry, uncontrolled
             hypertension or clinically significant arrhythmias not controlled by medication).

          -  Known immunosuppressive disease or active systemic autoimmune disease such as systemic
             lupus erythematosus, human immunodeficiency virus infection, Hepatitis B, or Hepatitis
             C, or has taken an immunosuppressive agent within 4 weeks prior to the start of SL-701
             treatment. Patients with vitiligo, type 1 diabetes mellitus, hypothyroidism due to
             autoimmune condition only requiring hormone replacement therapy, psoriasis not
             requiring systemic therapy, or conditions not expected to recur in the absence of an
             external trigger are permitted to enroll.

          -  Any condition which in the investigator's opinion makes the patient unsuitable for
             study participation.

          -  Requires therapeutic anticoagulation with warfarin at baseline; patients must be off
             warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to starting
             study drug; however, therapeutic or prophylactic therapy with low-molecular weight
             heparin is allowed.

          -  Has history of known coagulopathy that increases risk of bleeding or a history of
             clinically significant hemorrhage within 12 months of start of study drug.

          -  Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than
             those that are ≤Grade 1 and either post-operative or stable on at least 2 consecutive
             MRI scans

          -  Has gastrointestinal bleeding or any other hemorrhage/bleeding event National Cancer
             Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) >Grade 3 within
             6 months of start of study drug.