Treatment of advanced solid tumors with PRL3-ZUMAB

An Open Label Phase II Study of the Efficacy and Tolerability of PRL3-ZUMAB and Predictive Biomarkers in Advanced Solid Tumours

This study is testing a new treatment called PRL3-ZUMAB to see if it can help people with advanced solid tumors, like gastric cancer and liver cancer, who haven't had success with other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 21 Years and up
• Sex: All
• Sponsor: National Cancer Centre, Singapore (Academic / other)
• Drugs / interventions: ZUMAB, chemotherapy, radiation, immunotherapy
• Locations: 1 site (Singapore)
• Trial ID: NCT04118114 on ClinicalTrials.gov

What this trial studies

This Phase II clinical trial evaluates the efficacy and safety of PRL3-ZUMAB, an investigational monotherapy, in patients with advanced solid tumors that have not responded to standard treatments. Approximately 30 patients, including those with gastric cancer and hepatocellular carcinoma, will receive intravenous infusions of PRL3-ZUMAB every two weeks for up to 12 doses, with the possibility of continuation for those showing benefit. The study will also involve molecular profiling of tumor tissues to identify potential biomarkers for treatment response.

Who should consider this trial

Good fit: Ideal candidates include adults aged 21 and older with advanced solid tumors, specifically gastric cancer or hepatocellular carcinoma, who have failed previous standard therapies.

Not a fit: Patients with early-stage tumors or those who have not yet undergone standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors who have exhausted standard therapies.

How similar studies have performed: While this approach is novel, similar studies targeting specific tumor markers have shown promise in other contexts.

Eligibility criteria

Inclusion Criteria:

* Male or female patients 21 years of age or older at the time written informed consent is obtained.
* Histopathological- or cytological- documented advanced curatively unresectable solid tumors failing standard therapy.

  * For HCC must have failed at least 1 line of standard therapy.
  * For gastric cancer must have failed at least 2 line of standard therapy (inclusive of adjuvant treatment).
  * For other solid tumours must have failed at least 1 line of standard therapy.
* Progressive disease following the last treatment
* Life expectancy ≥ 4 months
* Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) score of ≤ 2 at study entry
* Recovery to Grade ≤ 1 by the Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE v 4.03), from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies for cancer, with the exception of non-clinically significant adverse events such as alopecia; biochemical abnormalities, or resolved to Grade ≤ 2: peripheral neuropathy; hypertension and proteinuria.
* Women of childbearing potential (WOCBP) must have a negative pregnancy test at study entry. Subjects not considered WOCBP are those without menses for 24 consecutive months, and those who have undergone hysterectomy and/or bilateral salpingo-oophorectomy. WOCBP must be willing to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of the study.
* Adequate organ and hematological function as evidenced by the following laboratory studies within 10 days of 1st treatment:

  * Absolute neutrophil count ≥ 1.0 x 10\^9/L.
  * Platelet count ≥ 75 x 10\^9/L. Hemoglobin ≥ 9 g/dL.
  * Prothrombin time and activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range.
  * Total bilirubin ≤ 1.5x ULN.
  * Aspartate aminotransferase and alanine aminotransferase ≤ 3 x ULN (≤ 5x ULN in the presence of liver mets).
  * For patients with hepatocellular carcinoma (HCC) Child Pugh score of ≤ B7.
  * Creatinine \< 1.5x ULN
* Evaluable or measurable disease by RECIST v1.1
* Patients with active Hepatitis B (defined as Hep B S Ag or DNA positive) need to be on anti-viral therapy while on PRL3-ZUMAB.

Exclusion Criteria:

* Untreated or symptomatic central nervous system metastases. Patients with treated brain metastases stable for 3 months are eligible to enroll.
* Major surgical procedures within 28 days prior to enrolment.
* Pregnant or breast-feeding females.
* Known HIV infection.
* Treatment with any of the following anti-cancer therapies prior to the first dose of study drugs within the stated time frames:

  * Prior chemotherapy ≤ 2 weeks of C1 Day 1 of PRL3-ZUMAB.
  * Biological therapy (e.g., antibodies) within a period of time that is ≤ 5 t1/2 or ≤ 3 weeks, whichever is shorter, prior to starting study drug.
  * Continuous or intermittent small molecule therapeutics within a period of time that is ≤ 5 t1/2 or ≤ 3 weeks (whichever is shorter) prior to starting study drug.
  * Any other investigational agents within a period of time that is ≤ 5 t1/2 or less than the cycle length used for that treatment or ≤ 4 weeks (whichever is shortest) prior to starting study drug.
  * Wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug.
* Patients requiring regular immunosuppressive medication for autoimmune disease or corticosteroid doses of \>10mg prednisolone for greater than 2 days
* Unable to provide informed consent.
* History of another cancer within the last 2 years, with the exception of

  * Curatively resected non-melanomatous skin cancer,
  * Curatively treated cervical carcinoma in-situ,
  * Prostate cancer treated with leuteinizing hormone-releasing hormone (LH-RH) agonists/pure antagonists for at least 2 months
* Prior stem cell or bone marrow transplant
* Vaccinated within 2 weeks from prior to the first administration of PRL3-ZUMAB

Where this trial is running

Singapore

• National Cancer Center Singapore — Singapore, Singapore (Recruiting)

Study contacts

• Principal investigator: Matthew Ng, MD — National Cancer Centre of Singapore
• Study coordinator: Matthew Ng, MD

Conditions Gastric Cancer; Hepatocellular Carcinoma; Advanced Solid Tumor