Metastatic Colorectal CancerPhase 1NCT04073615
A Study of Rivoceranib and Trifluridine/Tipiracil for Metastatic Colorectal Cancer (mCRC)
A Phase 1 study testing Rivoceranib and Trifluridine/Tipiracil in people with Metastatic Colorectal Cancer, run by Elevar Therapeutics at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Rivoceranib and Trifluridine/Tipiracil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 4 sitesUnited States
- Study dates
- 18 Nov 2019to 31 May 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3.0x ULN (≤5.0 × ULN for participants with liver involvement of their cancer)
- Bilirubin ≤1.5 × ULN
- Alkaline phosphatase ≤2.5 × ULN (≤5 × ULN with liver involvement of their cancer)
- International normalized ratio (INR) / partial thromboplastin time (PTT) ≤1.5 × ULN (Participants currently under treatment with anti-thrombotic agents such as warfarin or heparin with no abnormal coagulation values can participate in this study)
- Urinary protein <2+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥ 2+, a 24-hour urine or urine protein/creatinine ratio must be collected and must demonstrate <2 g of protein in 24 hours to allow participation in the study.
- Have an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
Who cannot join
- 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
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- 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
- 6. Active renal dysfunction that requires dialysis treatments
- 7. 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
- 8. Cardiac arrhythmias requiring antiarrhythmic therapy (beta-blockers or digoxin are permitted)
- 9. 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)
- 10. History of antiangiogenic drug class-related severe adverse reactions, including uncontrolled hypertension or others related to prior therapy discontinuation and/or those that may indicate a higher risk to a participant' safety, in the Investigator's opinion, if provided further antiangiogenic treatment.
- 11. History of vascular disease including arterial or venous embolic events (pulmonary embolism), other than hypertension, within 6 months prior to Cycle 1 Day 1 (for example, hypertensive crisis, hypertensive encephalopathy, stroke or transient ischemic attack [TIA], or significant peripheral vascular diseases) that, in the Investigator's opinion, may pose a risk to the participant on VEGF inhibitor therapy.
- 12. History of clinically significant thrombosis within 3 months prior to first dose of study drug that, in the Investigator's opinion, may place the participant at risk of side effects from antiangiogenics medications
- 13. History of bleeding diathesis or clinically significant bleeding within 14 days prior to first dose of study drug
- 14. Therapy with systemic anticoagulant or antithrombotic agents within 7 days prior to first dose of study drug that in the Investigator's opinion could interfere with clotting. The maximum allowable daily dose of aspirin is 325 milligram (mg).
- 15. Participants with unstable seizure disorder requiring medication changes within 3 months of Cycle 1 Day 1 treatment
- 16. Untreated or active central nervous system (CNS) or leptomeningeal metastases. Participants are eligible if metastases have been treated and participants are neurologically returned to baseline or neurologically stable (expect for residual signs and symptoms related to the CNS treatment) for at least 4 weeks prior to first dose of study drug. In addition, participants must be either off corticosteroids, or on a stable dose or decreasing dose of ≤ 20 mg daily prednisone or prednisone-equivalent. A baseline radiological assessment of the brain will be performed on participants who have prior history of metastases with CNS involvement
- 17. History of clinically significant glomerulonephritis, biopsy-proven nephritis, crystal nephropathy or other renal insufficiencies
- 18. Unresolved adverse reactions >Grade 1 excluding peripheral neuropathy or treatment related myelosuppression
- 19. Known hypersensitivity to any of the study drugs, study drug classes, or any components of study drug formulations
- 20. Inability to swallow oral medications
- 21. An active malabsorption condition, or any other condition that in the opinion of the Investigator might affect the absorption of study drug
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Northwestern University
Chicago, Illinois, 60611
Vanderbilt University School of Medicine
Nashville, Tennessee, 37232
Florida Cancer Specialists
Sarasota, Florida, 34232
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Phase 1b/2 Open-label Study to Evaluate the Safety, Tolerability and Efficacy of Rivoceranib or Trifluridine/Tipiracil as Monotherapies and Rivoceranib and Trifluridine/Tipiracil as Combination Therapy in Subjects With Metastatic Colorectal Cancer
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.
Read the detailed description
This a multicenter open-label study comparing safety, tolerability and efficacy of rivoceranib and trifluridine/tipiracil monotherapies, and the combination of rivoceranib plus trifluridine/tipiracil in participants with mCRC. Participants with histologically or cytologically definitive adenocarcinoma of the colon or rectum who have progressed following standard of care therapy for colorectal cancer (CRC) will be randomly assigned (1:1:2) to rivoceranib, trifluridine/tipiracil or rivoceranib plus trifluridine/tipiracil treatment groups.
The study will consist of an initial phase 1b portion to assess the safety of and determine the RP2D of rivoceranib in combination with trifluridine/tipiracil. A subsequent phase 2 portion will assess the primary endpoint of progression free survival (PFS) by investigator assessment. When a participant discontinues rivoceranib and/or trifluridine/tipiracil for any reason, the participant will enter the 12-month survival follow-up period until withdrawal of consent from the study, lost to follow-up, end of the study or death, whichever occurs earlier.
The maximum duration of the study is estimated to be 36 months, which includes screening, treatment, and follow-up phases.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Rivoceranib, Trifluridine/Tipiracil
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivoceranibDrug
Also called Rivoceranib Mesylate, Apatinib Mesylate, Apatinib
Film-coated tablets
Trifluridine/TipiracilDrug
Also called Lonsurf
Film-coated tablets
| Study group | Role | What they receive |
|---|---|---|
| Rivoceranib | Experimental | Participants will receive an oral dose of rivoceranib once per day on Days 1 through 28 of each 28-day cycle. Receives: 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. Receives: 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. Receives: Drug: Rivoceranib; Drug: Trifluridine/Tipiracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
(Phase 1b) Percentage of Participants with Dose-limiting Toxicity (DLT) During Cycle 1
Measured: Baseline up to 28 days
(Phase 1b) Number of Participants with Adverse Events (AEs)investigator assessment
Measured: Baseline up to 3 years
(Phase 1b) Number of Participants with Serious Adverse Events (SAEs)
Measured: 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
Measured: Up to approximately 3 years
Secondary outcomes (6)
(Phase 1b and Phase 2) Overall Survival (OS)
OS is the time from participant enrollment until death from any cause.
Measured: Up to approximately 3 years
(Phase 2) Objective Response Rate (ORR)
ORR per RECIST v1.1 by Investigator Assessment is defined as percentage of participants who will achieve confirmed Complete Response (CR) or Partial Response (PR).
Measured: Up to approximately 3 years
Duration of Response (DoR)
DoR per RECIST v1.1 by investigator assessment.
Measured: Up to approximately 3 years
Time to Progression (TTP)
TTP per RECIST v1.1 by investigator assessment.
Measured: Up to approximately 3 years
(Phase 2) Disease Control Rate (DCR)
DCR per RECIST v1.1 by investigator assessment.
Measured: Up to approximately 3 years
(Phase 1b and 2) Number of Participants with Adverse Events (AEs) that Worsen in Severity as Defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Measured: Up to approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2019
- Study start18 Nov 2019
- Primary completion31 May 2023
- Study completion31 May 2023
Why it stopped: Phase 2 portion of the study was not performed due to redirection of the rivoceranib development plan by the Sponsor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Elevar Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04073615
- Sponsor's protocol ID
- RM-110
- Status last verified
- Apr 2024
- First submitted
- 26 Aug 2019
- Last updated
- 2 May 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b/2 Open-label Study to Evaluate the Safety, Tolerability and Efficacy of Rivoceranib or Trifluridine/Tipiracil as Monotherapies and Rivoceranib and Trifluridine/Tipiracil as Combination Therapy in Subjects With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT04073615
- Acronym / sponsor ID
- RM-110
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Phase 2 portion of the study was not performed due to redirection of the rivoceranib development plan by the Sponsor.
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Elevar TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 18 Nov 2019 (actual)
- Primary completion
- 31 May 2023 (actual)
- Study completion
- 31 May 2023 (actual)
- First posted
- 29 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This a multicenter open-label study comparing safety, tolerability and efficacy of rivoceranib and trifluridine/tipiracil monotherapies, and the combination of rivoceranib plus trifluridine/tipiracil in participants with mCRC. Participants with histologically or cytologically definitive adenocarcinoma of the colon or rectum who have progressed following standard of care therapy for colorectal cancer (CRC) will be randomly assigned (1:1:2) to rivoceranib, trifluridine/tipiracil or rivoceranib plus trifluridine/tipiracil treatment groups.
The study will consist of an initial phase 1b portion to assess the safety of and determine the RP2D of rivoceranib in combination with trifluridine/tipiracil. A subsequent phase 2 portion will assess the primary endpoint of progression free survival (PFS) by investigator assessment. When a participant discontinues rivoceranib and/or trifluridine/tipiracil for any reason, the participant will enter the 12-month survival follow-up period until withdrawal of consent from the study, lost to follow-up, end of the study or death, whichever occurs earlier.
The maximum duration of the study is estimated to be 36 months, which includes screening, treatment, and follow-up phases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rivoceranib | Experimental | Drug: RivoceranibParticipants will receive an oral dose of rivoceranib once per day on Days 1 through 28 of each 28-day cycle. |
| Trifluridine/tipiracil | Active comparator | Drug: Trifluridine/TipiracilParticipants 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. |
| Rivoceranib and trifluridine/tipiracil | Experimental | Drug: Rivoceranib, Drug: Trifluridine/TipiracilParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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:
- 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
Key exclusion criteria (27 listed)
- 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:
- 6. Active renal dysfunction that requires dialysis treatments
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RivoceranibAlso: Rivoceranib Mesylate, Apatinib Mesylate, ApatinibFilm-coated tablets | Drug | Rivoceranib, Rivoceranib and trifluridine/tipiracil |
| Trifluridine/TipiracilAlso: LonsurfFilm-coated tablets | Drug | Rivoceranib and trifluridine/tipiracil, Trifluridine/tipiracil |
Primary outcome
(Phase 1b) Percentage of Participants with Dose-limiting Toxicity (DLT) During Cycle 1
Time frame: Baseline up to 28 days
(Phase 1b) Number of Participants with Adverse Events (AEs)investigator assessment
Time frame: Baseline up to 3 years
(Phase 1b) Number of Participants with Serious Adverse Events (SAEs)
Time frame: 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
Time frame: Up to approximately 3 years
6 secondary outcomes
(Phase 1b and Phase 2) Overall Survival (OS)
Time frame: Up to approximately 3 years
(Phase 2) Objective Response Rate (ORR)
Time frame: Up to approximately 3 years
Duration of Response (DoR)
Time frame: Up to approximately 3 years
Time to Progression (TTP)
Time frame: Up to approximately 3 years
(Phase 2) Disease Control Rate (DCR)
Time frame: Up to approximately 3 years
(Phase 1b and 2) Number of Participants with Adverse Events (AEs) that Worsen in Severity as Defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Time frame: Up to approximately 3 years
Results and safety
The study was stopped early (reason given: Phase 2 portion of the study was not performed due to redirection of the rivoceranib development plan by the Sponsor.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2024.
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CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rivoceranib and Trifluridine/Tipiracil in people with Metastatic Colorectal Cancer, run by Elevar Therapeutics at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Phase 2 portion of the study was not performed due to redirection of the rivoceranib development plan by the Sponsor.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
(Phase 1b) Percentage of Participants with Dose-limiting Toxicity (DLT) During Cycle 1 (time frame: Baseline up to 28 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2024.