SOR-C13 in Treating Patients With Advanced Refractory Solid Tumors

• ClinicalTrials.gov Identifier: NCT03784677
• Recruitment Status: Recruiting
• First Posted: December 24, 2018
• Last Update Posted: October 24, 2022
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: TRPV6 Calcium Channel Inhibitor SOR-C13	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of SOR-C13 in Patients With Advanced Solid Tumors
• Actual Study Start Date: July 29, 2019
• Estimated Primary Completion Date: August 9, 2023
• Estimated Study Completion Date: August 9, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment (TRPV6 calcium channel inhibitor SOR-C13); Patients 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.	Drug: TRPV6 Calcium Channel Inhibitor SOR-C13; Given IV; Other Name: SOR-C13

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events and serious adverse events [ Time Frame: Up to 30 days after last dose ]
   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.
2. Incidence of >= grade 2 adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 30 days after last dose ]
3. Dose-limiting toxicities [ Time Frame: Up to 28 days ]
4. Withdrawals from the study due to treatment-related adverse events will be documented [ Time Frame: Up to 30 days after last dose ]
5. Change of the treatment regimen such as dose delay and dose reduction over time by dose level due to treatment-related adverse events [ Time Frame: Up to 30 days after last dose ]

Secondary Outcome Measures :

1. Objective responses [ Time Frame: Up to 6 months ]
   Defined as complete response(CR)s and partial response (PR).
2. Clinical benefit [ Time Frame: Up to 6 months ]
   Defined as stable disease (SD)/CR/PR according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
3. Predictive biomarkers [ Time Frame: Up to 6 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Siqing Fu; 713-792-4318; siqingfu@mdanderson.org

Locations

United States, Texas

M D Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Siqing Fu 713-563-0181

Principal Investigator: Siqing Fu

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Siqing Fu; M.D. Anderson Cancer Center

More Information

Additional Information:

MD Anderson Cancer Center Website 

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT03784677
• Other Study ID Numbers: 2018-0680; NCI-2018-02835 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2018-0680 ( Other Identifier: M D Anderson Cancer Center )
• First Posted: December 24, 2018
• Last Update Posted: October 24, 2022
• Last Verified: October 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Prostatic Neoplasms; Neoplasms; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Prostatic Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; SOR-C13; Calcium; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Antineoplastic Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action