A Study to Evaluate Safety, Tolerability, and Efficacy Profile of Rivoceranib With Paclitaxel in Advanced Gastric or Gastroesophageal Junction Cancer

NCT03707028 | Terminated Phase 1

• 1 other identifier: LSK-RM109
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-center, single-arm, dose escalation and dose expansion Phase I/IIa study designed to determine the recommended Phase 2 dose (RP2D) and the safety and tolerability profile along with preliminary signs of efficacy of rivoceranib in combination with paclitaxel as a second-line therapy in advanced, recurrent and/or metastatic gastric or gastroesophageal junction cancer. This study will also characterize the pharmacokinetic (PK) parameters of rivoceranib and paclitaxel when given in combination.

Conditions

Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• Phase I: Incidence of Dose-Limiting Toxicities (DLT) During Cycle 1

  The number and proportion of participants experiencing DLTs will be reported by dose level, based on DLT observations during Cycle 1. Each Cycle is 28 days.

  Cycle 1 (first 28 days)

• Phase I: Number of Participants Reporting Adverse Events (AEs) and Serious AEs (SAEs)

  An AE is any untoward medical occurrence in a participant or participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, or important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent 1 of the other outcomes listed above.

  Up to 24 months

• Phase II: Objective Response Rate (ORR)

  ORR is the percentage of participants who achieve objective tumor response (complete response \[CR\] or partial response \[PR\]) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria for response.

  Every other cycle (each cycle is 28 days) until end of study, assessed up to 24 months

Secondary Outcomes (19)

• Phase I: Maximum Observed Concentration (Cmax)

  Day 1 & 15 of Cycle 1 (each cycle is 28 days)

• Phase I: Time to Maximum Observed Concentration (tmax)

  Day 1 & 15 of Cycle 1 (each cycle is 28 days)

• Phase I: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC0-t)

  Day 1 & 15 of Cycle 1 (each cycle is 28 days)

• Phase I: Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-∞)

  Day 1 & 15 of Cycle 1 (each cycle is 28 days)

• Phase I: Terminal Half-life (t1/2)

  Day 1 & 15 of Cycle 1 (each cycle is 28 days)

Study Arms (1)

Rivoceranib with Paclitaxel

EXPERIMENTAL

Participants will receive oral daily doses of rivoceranib per 28-day cycle (as its mesylate salt) with a fixed dose of paclitaxel given intravenously on Day 1, Day 8, and Day 15 of the 28-day cycle.

Drug: Rivoceranib; Drug: Paclitaxel

Interventions

Rivoceranib DRUG

Film-coated tablet

Also known as: Apatinib

Rivoceranib with Paclitaxel

Paclitaxel DRUG

Solution administered intravenously

Also known as: Taxol

Rivoceranib with Paclitaxel

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with documented locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer refractory to or relapsing after first line platinum and fluoropyrimidine containing chemotherapy (with or without trastuzumab) with an indication for therapy with paclitaxel and an antiangiogenic agent. If disease progression occurs during or within 6 months after completion of any adjuvant chemotherapy, this therapy is considered a first-line chemotherapy for participant eligibility.
• Participants who have provided tumor tissue prior to initiation of first-line therapy and have provided or can provide tumor tissue prior to screening in this study. This will be optional for Phase I participants. Tumor tissue must not have been irradiated.
• Participants who have at least 1 measurable lesion as defined by RECIST v1.1. This will be optional for Phase I participants.
• Adequate bone marrow, renal, and liver function evidenced by:
• Adequate renal function, defined as meeting any 1 of the following criteria:
• i. Serum creatinine \<1.5 × upper limit of normal (ULN). ii. Creatinine clearance based on the Cockcroft-Gault estimate ≥50 milliliters per minute (mL/min) or creatinine clearance based on urine collection (12 or 24 hours) ≥50 mL/min.
• iii. In addition, urinary protein should be \<2+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥2+, then a 24 hour urine or urine protein/creatinine ratio must be collected and must demonstrate \<2 g of protein in 24 hours.
• c) Hepatic: Serum bilirubin \<1.5 × ULN, aspartate and alanine aminotransferase ≤3.0 × ULN (≤5.0 × UNL, if with liver metastases). If liver and/or bone metastases alkaline phosphatase ≤5 × ULN.
• Blood coagulation tests: Prothrombin time and international normalized ratio ≤1.5 × ULN.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Estimated life expectancy of at least 12 weeks.
• Ability to swallow the study drug without chewing, breaking, crushing, opening or otherwise altering the product formulation. If vomiting occurs, the dose will not be replaced. Antiemetics must be used at efficacious doses.
• No major gastrointestinal disease (e.g., chronic diarrheal disease) or intestinal surgery that can jeopardize drug absorption.

You may not qualify if:

• Prior use of taxane (paclitaxel or docetaxel) or any contraindication for therapy with paclitaxel.
• Previous treatment with rivoceranib or any other systemic therapy with a vascular endothelial growth factor (VEGF) pathway inhibitor.
• Known hypersensitivity to rivoceranib or any component of its formulation or history of severe adverse events, including uncontrolled hypertension or other common anti-angiogenesis drug class effects during prior exposure to vascular inhibitors.
• Any unresolved toxicity Grade \>1 (except alopecia) from previous anticancer therapy (including radiotherapy).
• Has history of another malignancy within 2 years prior to screening. Participants with the following are eligible for this study if, in the opinion of the investigator, they do not pose a significant risk to life expectancy:
• Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in situ (Tis).
• Curatively treated cervical carcinoma in situ.
• Thyroid papillary cancer with prior treatment.
• Carcinoma of the skin without melanomatous features.
• Prostate cancer which has been surgically or medically treated and not likely to recur within 2 years.
• Has received prior anticancer therapy within 3 weeks before Cycle 1 Day 1. Traditional herbal remedies with anti-infective, immune stimulating, or anticancer properties are not allowed from screening throughout the entire period of study participation.
• Current or recent (within 10 days of Cycle 1 Day 1) use of full dose oral or parenteral anticoagulants or other thrombolytic agents for therapeutic (as opposed to prophylactic) purposes, clinically serious non-healing wounds, or incompletely healed bone fracture. A maximum dose of 325 milligrams (mg)/day of aspirin is allowed.
• Participants who had therapeutic paracentesis of ascites (\>1 liter \[L\]) within the 2 months prior to starting study treatment or who, in the opinion of the investigator, will likely need therapeutic paracentesis of ascites (\>1L) within 2 months of Cycle 1 Day 1.
• Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9, and CYP2C19.
• Active bacterial infections (including tuberculosis and syphilis) requiring systemic antibiotic therapy.

Sponsors & Collaborators

• Elevar Therapeutics: lead

Study Sites (1)

Asan Medical Center

Seoul, 05505, South Korea

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

apatinib; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Min-Hee Ryu, Dr.

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 16, 2018
• Study Start: October 1, 2018
• Primary Completion: August 24, 2021
• Study Completion: August 24, 2021
• Last Updated: April 11, 2022

Record last verified: 2022-04

Locations

KR (1)