Clinical Trials /

SOR-C13 in Treating Patients With Advanced Refractory Solid Tumors

NCT03784677

Description:

This phase I trial studies the side effects and best dose of SOR-C13 in treating patients with solid tumors that have spread to other places in the body (advanced) and does not respond to treatment. Drugs used in chemotherapy, such as SOR-C13, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Related Conditions:
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: SOR-C13 in Treating Patients With Advanced Refractory Solid Tumors
  • Official Title: A Phase I Study of SOR-C13 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 2018-0680
  • SECONDARY ID: NCI-2018-02835
  • SECONDARY ID: 2018-0680
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03784677

Conditions

  • Advanced Malignant Solid Neoplasm
  • Refractory Malignant Solid Neoplasm
  • Refractory Ovarian Carcinoma
  • Refractory Pancreatic Carcinoma
  • Stage II Pancreatic Cancer AJCC v8
  • Stage IIA Pancreatic Cancer AJCC v8
  • Stage IIB Pancreatic Cancer AJCC v8
  • Stage III Ovarian Cancer AJCC v8
  • Stage III Pancreatic Cancer AJCC v8
  • Stage III Prostate Cancer AJCC v8
  • Stage IIIA Ovarian Cancer AJCC v8
  • Stage IIIA Prostate Cancer AJCC v8
  • Stage IIIB Ovarian Cancer AJCC v8
  • Stage IIIB Prostate Cancer AJCC v8
  • Stage IIIC Ovarian Cancer AJCC v8
  • Stage IIIC Prostate Cancer AJCC v8
  • Stage IV Ovarian Cancer AJCC v8
  • Stage IV Pancreatic Cancer AJCC v8
  • Stage IV Prostate Cancer AJCC v8
  • Stage IVA Ovarian Cancer AJCC v8
  • Stage IVA Prostate Cancer AJCC v8
  • Stage IVB Ovarian Cancer AJCC v8
  • Stage IVB Prostate Cancer AJCC v8

Interventions

DrugSynonymsArms
TRPV6 Calcium Channel Inhibitor SOR-C13SOR-C13Treatment (TRPV6 calcium channel inhibitor SOR-C13)

Purpose

This phase I trial studies the side effects and best dose of SOR-C13 in treating patients with solid tumors that have spread to other places in the body (advanced) and does not respond to treatment. Drugs used in chemotherapy, such as SOR-C13, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To define the maximum tolerated doses (MTD) of TRPV6 calcium channel inhibitor SOR-C13
      (SOR-C13) in subjects with advanced solid tumor cancers of epithelial origin.

      II. To define the safety profiles of the treatment.

      SECONDARY OBJECTIVES:

      I. To evaluate clinical response signals to the treatment. II. To assess predictive
      biomarkers (baseline molecular mutation status) and/or resistant pathways by comparing
      molecular signatures at baseline versus at time of relapse in patients who have achieved
      objective responses.

      OUTLINE: This is a dose-escalation study.

      Patients receive TRPV6 calcium channel inhibitor SOR-C13 intravenously (IV) over 2 hours on
      days 1, 2, 8, 9, 15, 16, 22, and 23. Cycles repeat every 28 days in the absence of disease
      progression or unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (TRPV6 calcium channel inhibitor SOR-C13)ExperimentalPatients receive TRPV6 calcium channel inhibitor SOR-C13 IV over 2 hours on days 1, 2, 8, 9, 15, 16, 22, and 23. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • TRPV6 Calcium Channel Inhibitor SOR-C13

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects with a histologic diagnosis of solid tumor cancers of epithelial origin
             (metastatic epithelial ovarian, pancreatic and prostate cancers are preferred since
             these tumor types have TRPV6 overexpression)

          -  Subjects with advanced refractory cancer for which standard curative or palliative
             measures do not exist or are no longer effective. There is no limitation on the number
             or types of prior therapy

          -  Patients must have measurable or evaluable disease, as defined by Response Evaluation
             Criteria in Solid Tumors 1.1 (RECIST1.1)

          -  Women of child-bearing potential (who are not postmenopausal for at least one year or
             are not surgically sterile) and men must agree to use adequate contraception (e.g.,
             hormonal, barrier device, or abstinence) prior to study entry, for the duration of
             study participation, and for 30 days after the last dose the study agents

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 to 1

          -  Neutrophils >= 1,500 /uL

          -  Platelets >= 100,000 /uL

          -  Total bilirubin =< 1.5 x ULN (upper limit of normal) (except patients with Gilbert's
             syndrome, who must have a total bilirubin =< 3.0 mg/dL)

          -  Alanine aminotransferase (ALT) =< 2.5 x ULN or =< 5 x ULN if liver metastases persist

          -  Serum creatinine =< 1.5 x ULN or calculated creatinine clearance >= 45 mL/minute by
             the Cockcroft-Gault method

          -  Albumin >= 3.0 g/dL (>= 3.0 g/L)

          -  International normalized ratio (INR) (international normalized ratio) =< 1.4

          -  Patients should be able to read and fully understand the requirements of the trial, be
             willing to comply with all trial visits and assessments, and be willing and able to
             sign an Institutional Review Board (IRB)-approved written informed consent document

          -  Subjects must have recovered from major infections and/or surgical procedures and, in
             the opinion of the investigator, not have a significant active concurrent medical
             illness precluding protocol treatment

          -  Patients agree to provide archival tissue block or 10 formalin-fixed paraffin-embedded
             (FFPE) slides paraffin for use in pharmacodynamics correlative studies

        Exclusion Criteria:

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection requiring intravenous antibiotics, symptomatic congestive heart failure (New
             York Heart Association [NYHA] class III or IV), or history of myocardial infarction,
             unstable angina, stroke or transient ischemic attack within 6 months prior to study
             enrollment

          -  History of clinically significant allergic reactions to the study drugs or their
             analogs, or any component of the products

          -  Any treatment specific for systemic tumor control within 3 weeks prior to the
             initiation of the study drugs; or within 2 weeks if cytotoxic agents were given weekly
             (within 6 weeks for nitrosoureas or mitomycin C), or within 5 half-lives for targeted
             agents with half-lives and pharmacodynamic effects lasting less than 4 days, or
             failure to recover from toxic effects of any therapy prior to the study drug treatment

          -  Patients who have not recovered from major surgical procedure, or significant
             traumatic injury (i.e., still need additional medical care for these issues)

          -  History of any of the following cardiovascular events or conditions within the past 6
             months prior to enrollment: myocardial infarction, unstable angina, cerebrovascular
             accident or transient ischemic attack, New York Heart Association class >= II chronic
             heart failure, hypokalemia, significant arrhythmia

               -  Corrected QC (QTc) interval > 430 msec or use of drugs that prolong the QT
                  interval at screening; family history of long QT syndrome

               -  Significant arrhythmias are defined as symptoms of syncope or severe palpitations
                  (palpitations requiring referral to cardiac monitoring), or electrocardiography
                  (ECG) findings of supraventricular tachycardia (including atrial fibrillation or
                  atrial flutter) or ventricular tachycardia (including ventricular fibrillation)
                  or ventricular ectopy (ventricular premature depolarization)

          -  Clinically significant and uncontrolled major medical condition(s) that places the
             subject at an unacceptably high risk for toxicities. These include, but are not
             limited to: active infections, symptomatic pulmonary disease, inadequate pulmonary
             function, seizure disorder, or psychiatric illness

          -  Current use of more than one antihypertensive medication

          -  For patients receiving antihypertensive medication: systolic blood pressure < 120 mm
             Hg and/or diastolic blood pressure < 70 mm Hg at screening

          -  A known diagnosis of human immunodeficiency virus (HIV) infection or acquired immune
             deficiency syndrome (AIDS), acute or chronic hepatitis B or hepatitis C infection, as
             determined by medical history

          -  Major surgical procedure within 4 weeks prior to enrollment

          -  Lactating or pregnant female

          -  Females of childbearing potential and males not using adequate birth control

          -  Current treatment or treatment within 4 weeks of screening with bisphosphonates

          -  Hypocalcemia at screening

          -  History of acute pancreatitis within 6 months prior to screening

          -  Known hypoparathyroidism, pseudohypoparathyroidism, or vitamin D deficiency, or
             clinical evidence of other conditions known to associated with hypocalcemia, including
             hypoalbuminemia, hyperphosphatemia, hypomagnesemia

          -  Current treatment or treatment within 4 weeks of screening with drugs known to reduce
             serum calcium levels, including: bisphosphonates, antiepileptic drugs, cinacalcet,
             macrolide antibiotics (such as erythromycin, azithromycin), large doses of
             corticosteroids (> 20 mg/day of prednisone or equivalent), or any IV use of
             corticosteroids. In addition, long-term use (defined as ongoing use for >= 4 weeks) of
             corticosteroids within 8 weeks of screening is prohibited

          -  Symptomatic and uncontrolled metastasis to the central nervous system or
             leptomeningeal or lymphangitic carcinomatosis

          -  Grade 2 or higher peripheral neuropathy

          -  Human immunodeficiency virus requiring highly active antiretroviral therapy (HAART)
             treatment due to unknown drug-drug interactions or has known active hepatitis B (e.g.,
             hepatitis B surface antigen [HBsAg] reactive or C virus (e.g., hepatitis C virus [HCV]
             ribonucleic acid [RNA] [quantitative] is detected) infection
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events and serious adverse events
Time Frame:Up to 30 days after last dose
Safety Issue:
Description:Will assess clinical symptoms and laboratory values, evaluate vital signs and perform physical exams, with a special attention to treatment- related fatigue, gastrointestinal (GI) symptoms, cardiovascular events, myelosuppression, and neurotoxicity.

Secondary Outcome Measures

Measure:Objective responses
Time Frame:Up to 6 months
Safety Issue:
Description:Defined as complete response(CR)s and partial response (PR).
Measure:Clinical benefit
Time Frame:Up to 6 months
Safety Issue:
Description:Defined as stable disease (SD)/CR/PR according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure:Predictive biomarkers
Time Frame:Up to 6 months
Safety Issue:
Description:Fisher exact test is used to associate potential biomarkers with SD >= 6 months/CR/PR. Next generation sequencing for targeted exome panel and NanoString arrays are used to reveal potential biomarkers of acquired resistance.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

August 2, 2019