First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors

NCT03616574 | Completed Phase 1 FDA Drug

• 1 other identifier: HS-CA102N-101
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

Brief Summary

Study HS-CA102N-101 is a phase 1, two part (dose escalation, dose expansion), multicenter, non-randomized, open-label, multiple dose, first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil (LONSURF) in subjects with advanced solid tumors. CA102N will be evaluated in subjects with locally advanced or metastatic solid tumours for which no effective therapy is available in Part 1 (dose escalation) and in subjects with relapsed or refractory locally advanced or metastatic colorectal cancer (mCRC) after prior oxaliplatin and irinotecan-based chemotherapy in Part 2 (dose expansion).

Conditions

Advanced or Metastatic Solid Tumors; Advanced or Metastatic Colorectal Cancer (mCRC)

Outcome Measures

Primary Outcomes (1)

• Number of subjects with treatment-related adverse events as assessed by NCI-CTCAE v5.0

  The primary endpoint for the study is the safety and tolerability of CA102N monotherapy and CA102N combined with trifluridine/tipiracil (LONSURF) as determined according to the NCI-CTCAE version 5.0.

  The safety measures will be assessed and recorded throughout the trial until 30 days following treatment termination (an average of 1 year).

Secondary Outcomes (1)

• Serum concentration of CA102N

  Serum sampling timepoints: predose, 0.5,1, 2, 4, 8, 12, 24, 48, and 72 hours postdose CA102N on Days 1 and 15 at Cycle 1 (each cycle is 28 days).

Other Outcomes (2)

• Tumor response according to RECIST v1.1

  Tumor response will be evaluated after every 2 cycles of treatment (each cycle is 28 days) until the subject starts alternative anti-cancer treatment or develops progressive disease, whichever occurs first (an average of 1 year).

• Analysis of urinary COX-2 metabolites by LC-MS/MS

  Urine samples will be collected at predose, 8 and 72 hours postdose CA102N on Days 1 and 15 at Cycle 1, at predose of each subsequent cycle (each cycle is 28 days), until the termination visit (an average of 1 year after Cycle 1 Day 1).

Study Arms (3)

Dose Escalation - CA102N Monotherapy

EXPERIMENTAL

0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 of a 28-day cycle

Drug: CA102N

Dose Escalation - CA102N plus LONSURF

EXPERIMENTAL

0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle

Drug: CA102N; Drug: LONSURF

Dose Expansion - CA102N plus LONSURF

EXPERIMENTAL

The preliminary RP2D of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle

Drug: CA102N; Drug: LONSURF

Interventions

CA102N DRUG

CA102N is a covalently bound conjugate of the biological polymer sodium hyaluronate (NaHA) and nimesulide (Nim).

Also known as: Nim-HA Conjugate

Dose Escalation - CA102N Monotherapy; Dose Escalation - CA102N plus LONSURF; Dose Expansion - CA102N plus LONSURF

LONSURF DRUG

LONSURF is a cytotoxic combination treatment of 2 new drugs: trifluridine, a thymidine-based nucleoside analog, and tipiracil, an inhibitor of thymidine phosphorylase.

Also known as: Trifluridine/Tipiracil

Dose Escalation - CA102N plus LONSURF; Dose Expansion - CA102N plus LONSURF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects enrolled in Part 1 must have histologically documented locally advanced or metastatic solid tumor for which there is no effective therapy available.
• Subjects enrolled in Part 2 must have histologically documented locally advanced or metastatic colorectal cancer that has relapsed after or is refractory to oxaliplatin and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.
• Age ≥18 years (US) or ≥20 years (Taiwan).
• ECOG performance status 0-1.
• Measurable or non-measurable disease based on RECIST version 1.1. Subjects enrolled in Part 2 must have at least one measurable lesion.
• Adequate organ function within 14 days before 1st dose of study drug, defined as:
• Platelet count ≥ 100,000/mm3.
• Hemoglobin ≥ 9.0 g/dL.
• Absolute neutrophil count ≥ 1500/mm3 (without hematopoietic growth factor support).
• Creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 50 mL/min as calculated using the modified Cockcroft-Gault equation.
• Aspartate aminotransferase: (i) ≤3 x ULN in subjects without liver metastasis or ≤5 x ULN in subjects with liver metastasis in CA102N monotherapy treatment group; (ii) ≤3 x ULN in subjects who will be treated with CA102N combined with trifluridine/tipiracil (LONSURF).
• Alanine aminotransferase: (i) ≤3 x ULN in subjects without liver metastasis or ≤5 x ULN in subjects with liver metastasis in CA102N monotherapy treatment group; (ii) ≤3 x ULN in subjects who will be treated with CA102N combined with trifluridine/tipiracil (LONSURF).
• Total bilirubin ≤1.5 x ULN (unless documented Gilbert's Syndrome).
• Has had an adequate treatment washout period prior to 1st dose of study drug defined as:
• No major surgery within the past 4 weeks.

You may not qualify if:

• For Part 2, active malignancies other than colorectal cancer.
• History of hypersensitivity or hepatotoxic reaction to nimesulide or to any excipient.
• Requiring therapeutic doses of anticoagulants.
• History or presence of a bleeding tendency or disorder.
• History of gastrointestinal bleed or perforation related to previous NSAID therapy.
• Presence or history of recurrent peptic ulcer or hemorrhage.
• History of cerebrovascular or other active bleeding.
• Myocardial infarction within the last 12 months, severe or unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) Class III or IV.
• History of a serious cardiac arrhythmia requiring treatment.
• Corrected QT prolongation using Fridericia formula (QTcF), of \> 450 msec for males or \> 470 msec for females based on a triplicate 12-lead ECG.
• Clinically significant lung disease (eg, interstitial pneumonia, interstitial lung disease, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) requiring continuous systemic corticosteroid treatment for 6 months before registration or who are suspected to have such diseases by imaging at Screening.
• Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks.
• Active autoimmune disease that has required systemic treatment in past 2 years.
• History of allogeneic transplantation requiring immunosuppressive therapy.
• Known positive test for hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV).

Sponsors & Collaborators

• Holy Stone Healthcare Co., Ltd: lead

Study Sites (3)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Jian YS, Chen CW, Lin CA, Yu HP, Lin HY, Liao MY, Wu SH, Lin YF, Lai PS. Hyaluronic acid-nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo. Int J Nanomedicine. 2017 Mar 27;12:2315-2333. doi: 10.2147/IJN.S120847. eCollection 2017.

  PMID: 28392690 BACKGROUND

• Pant S, Dragovich T, Lieu C, Jimeno A, Kundranda M, Menter D, Tchaparian E, Chen YC, Kopetz S. Phase 1 study of the safety, pharmacokinetics, and preliminary efficacy of CA102N as monotherapy and in combination with trifluridine-tipiracil in patients with locally advanced or metastatic solid tumors. Invest New Drugs. 2023 Feb;41(1):25-34. doi: 10.1007/s10637-022-01308-5. Epub 2022 Nov 4.

  PMID: 36331676 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Shubham Pant, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 (dose escalation) of the study will use a conventional 3+3 design (3 subjects per dose cohort, with the potential to add an additional 3 subjects if dose limiting toxicity \[DLT\] is observed at the same dose level at which the toxicity occurred). Enrollment will occur in 2 groups, CA102N monotherapy (Group A) and CA102N combination therapy (Group B). Subjects will be enrolled in Group A first. Once enrollment in Group A has been completed, subsequent subjects will be enrolled in Group B. In Part 2 of the study, the safety and tolerability of the preliminary RP2D of CA102N combined with trifluridine/tipiracil (LONSURF) will be further evaluated in up to 12 additional subjects with relapsed or refractory locally advanced or metastatic colorectal cancer who have previously received oxaliplatin and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

Study Record Dates

• First Submitted: June 26, 2018
• First Posted: August 6, 2018
• Study Start: April 9, 2019
• Primary Completion: February 8, 2022
• Study Completion: March 1, 2022
• Last Updated: September 21, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)