A Study of Rivoceranib and Trifluridine/Tipiracil for Metastatic Colorectal Cancer (mCRC)

NCT04073615 | Terminated Phase 1 FDA Drug

• 1 other identifier: RM-110
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to determine the recommended Phase 2 dose (RP2D) of rivoceranib when used in combination with trifluridine/tipiracil in participants with mCRC and to assess progression-free survival (PFS) in participants with mCRC.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (4)

• (Phase 1b) Percentage of Participants with Dose-limiting Toxicity (DLT) During Cycle 1

  Baseline up to 28 days

• (Phase 1b) Number of Participants with Adverse Events (AEs)investigator assessment

  Baseline up to 3 years

• (Phase 1b) Number of Participants with Serious Adverse Events (SAEs)

  Baseline up to 3 years

• (Phase 2) Progression Free Survival (PFS) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Investigator Assessment

  Up to approximately 3 years

Secondary Outcomes (6)

• (Phase 1b and Phase 2) Overall Survival (OS)

  Up to approximately 3 years

• (Phase 2) Objective Response Rate (ORR)

  Up to approximately 3 years

• Duration of Response (DoR)

  Up to approximately 3 years

• Time to Progression (TTP)

  Up to approximately 3 years

• (Phase 2) Disease Control Rate (DCR)

  Up to approximately 3 years

Study Arms (3)

Rivoceranib

EXPERIMENTAL

Participants will receive an oral dose of rivoceranib once per day on Days 1 through 28 of each 28-day cycle.

Drug: Rivoceranib

Trifluridine/tipiracil

ACTIVE COMPARATOR

Participants will receive an oral dose of Trifluridine/tipiracil twice per day with food, on Days 1 through 5 and Days 8 through 12 of each 28-day cycle.

Drug: Trifluridine/Tipiracil

Rivoceranib and trifluridine/tipiracil

EXPERIMENTAL

Participants will receive a daily oral dose of rivoceranib on Days 1 through 28 and the recommended phase 2 dose (RP2D) of trifluridine/tipiracil twice per day between Days 1 to 5 and 8 to 12 of each 28-day cycle.

Drug: Rivoceranib; Drug: Trifluridine/Tipiracil

Interventions

Rivoceranib DRUG

Film-coated tablets

Also known as: Rivoceranib Mesylate, Apatinib Mesylate, Apatinib

Rivoceranib; Rivoceranib and trifluridine/tipiracil

Trifluridine/Tipiracil DRUG

Film-coated tablets

Also known as: Lonsurf

Rivoceranib and trifluridine/tipiracil; Trifluridine/tipiracil

Eligibility Criteria

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

You may qualify if:

• Histological or cytological confirmation of the diagnosis of mCRC
• Failure to respond or be intolerant of at least 2 prior regimens of standard anti-cancer treatments (study treatment must be 3rd-line or greater for mCRC). Failed prior treatments may include:
• Fluoropyrimidines-based chemotherapy
• Irinotecan-based chemotherapy
• Oxaliplatin-based chemotherapy
• Anti-Vascular Endothelial Growth Factor (VEGF) biological therapy
• Anti-Epidermal Growth Factor Receptor (EGFR) therapy, if RAS wild-type
• Immunotherapy (for example, nivolumab, pembrolizumab and ipilimumab), in participants with Microsatellite Instability High/Deficient Mismatch Repair (MSI-H/dMMR). Participants who had received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy would be considered as 1 prior line of therapy
• Have progressed based on imaging during or within 3 months of the last administration of most recent therapy
• Have measurable disease, as defined by RECIST v1.1
• Adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days prior to Cycle 1 Day 1
• Absolute neutrophil count (ANC) ≥1,500/mm3
• Platelets ≥75,000/mm3
• Hemoglobin ≥9.0 g/dL
• Creatinine clearance (according to Cockcroft-Gault Equation or by 24 hr urine collection) \> 50 mL/min and serum creatinine \<1.0× upper limit of normal (ULN)

You may not qualify if:

• Prior treatment with rivoceranib or trifluridine/tipiracil
• Prior treatment with other VEGFR small molecule inhibitors (for example, regorafenib)
• Packed red blood cell transfusion or erythropoietin therapy within 14 days prior to first dose of study drug
• History of another malignancy within 3 years prior to Cycle 1 Day 1. A participant with the following malignancies is eligible for this study if, in the opinion of the Investigator, they do not pose a significant risk to life expectancy:
• Carcinoma of the skin without melanomatous features
• Curatively treated cervical carcinoma in situ
• Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in situ (Tis)
• Thyroid papillary cancer with prior treatment
• Prostate cancer which has been surgically or medically treated and not likely to recur within 3 years
• \. Active renal dysfunction that requires dialysis treatments
• \. Active cardiac disease including any of the following:
• Congestive heart failure New York Heart Association (NYHA) ≥Class 2
• Myocardial infarction less than 6 months before the start of Cycle 1 Day 1 of treatment
• \. Cardiac arrhythmias requiring antiarrhythmic therapy (beta-blockers or digoxin are permitted)
• \. History of uncontrolled hypertension (blood pressure ≥140/90 mmHg and/or change in antihypertensive medication within 7 days prior to first dose of study drug)

Sponsors & Collaborators

• Elevar Therapeutics: lead

Study Sites (4)

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Vanderbilt University School of Medicine

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

apatinib; 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 Design

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

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: August 29, 2019
• Study Start: November 18, 2019
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2023
• Last Updated: May 2, 2024

Record last verified: 2024-04

Locations

US (4)