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Trial record 2 of 6 for:    rivoceranib

Phase 1b/2 Study of Rivoceranib and Trifluridine/Tipiracil for Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04073615
Recruitment Status : Recruiting
First Posted : August 29, 2019
Last Update Posted : February 17, 2020
Sponsor:
Information provided by (Responsible Party):
Elevar Therapeutics

Brief Summary:
Comparing the efficacy of rivoceranib and trifluridine/tipiracil administered individually as monotherapies, as well as a rivocernib plus trifluridine/tipiracil combination therapy in the treatment of mCRC that is unresponsive to traditional chemotherapies.

Condition or disease Intervention/treatment Phase
CRC Drug: Rivoceranib Drug: Trifluridine/Tipiracil Phase 1 Phase 2

Detailed Description:

This a multicenter open-label study comparing safety, tolerability and efficacy of rivoceranib monotherapy, trifluridine/tipiracil monotherapy and the combination of rivoceranib plus trifluridine/tipiracil in subjects with mCRC. Subjects with histologically or cytologically definitive adenocarcinoma of the colon or rectum who have progressed following standard of care therapy for colorectal cancer 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 PFS by investigator assessment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 127 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b/2 Open-label Study to Evaluate the Safety, Tolerability and Efficacy of Rivoceranib and Trifluridine/Tipiracil as Monotherapies and as Combination Therapy in Subjects With Metastatic Colorectal Cancer
Actual Study Start Date : November 18, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Rivoceranib
Rivoceranib, 700 mg po, qd
Drug: Rivoceranib
Rivoceranib will be supplied as 100 mg and 200 mg film-coated tablets for oral administration.
Other Names:
  • Rivoceranib Mesylate
  • apatinib mesylate

Active Comparator: Trifluridine/tipiracil
35 mg/m2 po, bid
Drug: Trifluridine/Tipiracil
Trifluridine/tipiracil will be supplied as 15 mg trifluridine/6.14 mg tipiracil and 20 mg trifluridine/8.19 mg tipiracil tablets for PO administration.
Other Name: Lonsurf

Experimental: Rivoceranib and trifluridine/tipiracil
Rivoceranib, recommended phase 2 dose (RP2D) Trifluridine/Tipiracil, 35 mg/m2, po, bid
Drug: Rivoceranib
Rivoceranib will be supplied as 100 mg and 200 mg film-coated tablets for oral administration.
Other Names:
  • Rivoceranib Mesylate
  • apatinib mesylate

Drug: Trifluridine/Tipiracil
Trifluridine/tipiracil will be supplied as 15 mg trifluridine/6.14 mg tipiracil and 20 mg trifluridine/8.19 mg tipiracil tablets for PO administration.
Other Name: Lonsurf




Primary Outcome Measures :
  1. (Phase 1b) Determine Recommended Phase 2 Dose (RP2D) [ Time Frame: 3-6 months ]
    Determine RP2D of rivoceranib when used in combination with trifluridine/tipiracil in subjects with mCRC

  2. (Phase 2) PFS per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment [ Time Frame: 30-33 months ]
    Assess progression-free survival (PFS) in subjects with mCRC treated with rivoceranib alone, trifluridine/tipiracil alone or the combination of rivoceranib plus trifluridine/tipiracil


Secondary Outcome Measures :
  1. (Phase 1b) OS [ Time Frame: 3-6 months ]
    Determine the overall survival (OS) in subjects with mCRC taking rivoceranib in combination with trifluridine/tipiracil

  2. (Phase 1b) Safety Assessments [ Time Frame: 3-6 months ]
    Evaluate safety and tolerability (eg, new AEs, AEs present at baseline that worsen in severity during the study, and clinically significant laboratory abnormalities) of rivoceranib when used in combination with trifluridine/tipiracil in subjects with mCRC

  3. (Phase 2) OS [ Time Frame: 30-33 months ]
    Determine the overall survival (OS) in subjects with mCRC taking rivoceranib in combination with trifluridine/tipiracil

  4. (Phase 2) PFS [ Time Frame: 30-33 months ]
    Determine the Progression Free Survival (PFS) in subjects with mCRC taking rivoceranib in combination with trifluridine/tipiracil

  5. (Phase 2) ORR [ Time Frame: 30-33 months ]
    The Overall Response Rate (ORR) (complete response [CR] + partial response [PR] per RECIST v1.1 in subjects with mCRC taking rivoceranib in combination with trifluridine/tipiracil

  6. (Phase 2) DCR [ Time Frame: 30-33 months ]
    The Disease Control Rate (DCR) (CR + PR + stable disease) per RECIST v1.1 in subjects with mCRC taking rivoceranib in combination with trifluridine/tipiracil

  7. (Phase 2) Safety assessments [ Time Frame: 30-33 months ]
    Evaluate safety and tolerability (eg, new AEs, AEs present at baseline that worsen in severity during the study, and clinically significant laboratory abnormalities) of rivoceranib when used in combination with trifluridine/tipiracil in subjects with mCRC


Other Outcome Measures:
  1. (Phase 1b) Cmax [ Time Frame: 3-6 months ]
    Evaluate the maximum blood concentration (Cmax) of rivoceranib when used in combination with trifluridine/tipiracil

  2. (Phase 1b) Tmax [ Time Frame: 3-6 months ]
    Evaluate the time to maximum blood concentration (Tmax) of rivoceranib when used in combination with trifluridine/tipiracil

  3. (Phase 1b) AUC [ Time Frame: 3-6 months ]
    Evaluate the area under the curve (AUC) of rivoceranib when used in combination with trifluridine/tipiracil

  4. (Phase 1b) CL [ Time Frame: 3-6 months ]
    Evaluate the clearance (CL) of rivoceranib when used in combination with trifluridine/tipiracil

  5. (Phase 1b) t1/2 [ Time Frame: 3-6 months ]
    Evaluate the half-life (t1/2) of rivoceranib when used in combination with trifluridine/tipiracil

  6. (Phase 1b) RAS mutation status [ Time Frame: 3-6 months ]
    Correlate RAS status with OS



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects are eligible to be included in the study only if all the following criteria apply:

Disease related

  1. Histological or cytological confirmation of the diagnosis of mCRC
  2. 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 (e.g., nivolumab, pembrolizumab and ipilimumab), in patients with Microsatellite Instability High/Deficient Mismatch Repair (MSI-H/dMMR) Subjects 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
  3. Have progressed based on imaging during or within 3 months of the last administration of most recent standard therapy
  4. Have measurable disease, as defined by RECIST v1.1

    Laboratory

  5. Adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days prior to study treatment

    • 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× ULN
    • AST and ALT ≤3.0x ULN (≤5.0 × ULN for subjects with liver involvement of their cancer)
    • Bilirubin ≤1.5 × ULN
    • Alkaline phosphatase ≤2.5 × ULN (≤5 × ULN with liver involvement of their cancer)
    • INR/PTT ≤1.5 × ULN (Subjects currently under treatment with anti-thrombotic agents such as warfarin or heparin with no abnormal coagulation values can participate in this study)
  6. 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.

    Demographic

  7. Men and women at least 18 years of age at the time of study entry (or age of majority, if higher per local regulations)
  8. Have an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 Ethical/Other
  9. Able to understand and willing to provide written informed consent prior to enrollment in the study
  10. Female subjects who are of non-reproductive potential (i.e., post menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
  11. Male and female subjects of reproductive potential who agree to use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices, complete abstinence, or sterilized partner) and a barrier method (eg, condoms, cervical ring, sponge, etc.) during the period of therapy and for 3 months after the final dose of study drugs for male subjects and 6 months after the final dose of study drugs for female subjects. Female subjects should also refrain from breastfeeding and egg donation and males should refrain from sperm donation throughout this period.
  12. In the assessment of the Investigator, subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

  • Subjects will be excluded from the study if any of the following criteria apply:

Disease-related

  1. Prior treatment with rivoceranib or trifluridine/tipiracil
  2. Prior treatment with other VEGFR small molecule inhibitors (eg, regorafenib)
  3. Packed red blood cell transfusion or erythropoietin therapy within 14 days prior to first dose of study drug
  4. History of another malignancy within 3 years prior to Cycle 1 Day 1. A subject 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
  5. Prior chemotherapy, radiation therapy or major surgery within 4 weeks prior to first dose of study drug or presence of any non-healing wound (a procedure such as catheter placement is not considered to be major surgery). Prior immunotherapy within 12 weeks prior to first dose of study drug. Palliative radiotherapy to non-target lesions within 2 weeks prior to first dose of study drug or biopsy within 1 week prior to first dose of study drug is permitted
  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 subject's 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 (eg, 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 subject 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 subject 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 mg
  15. Subjects 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. Subjects are eligible if metastases have been treated and subjects 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, subjects 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 subjects 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 Ethical/Other
  22. Psychiatric illness/social situations that would limit compliance with study requirements
  23. History of drug or alcohol abuse within past 5 years
  24. Known seropositive requiring antiviral therapy for human immunodeficiency virus (HIV) infection
  25. Known seropositive requiring antiviral therapy for hepatitis B virus (HBV) infection OR evidence of active hepatitis B infection by detectable viral load if the antibody tests are positive.

    NOTE: A positive-HBcAb subject with an undetectable surface antigen and negative hepatitis B DNA test (eg, polymerase chain reaction [PCR] test) can be enrolled

  26. Known seropositive requiring anti-viral therapy for hepatitis C virus (HCV) infection OR subjects with positive hepatitis C virus antibody (Ab).

    NOTE: A positive Anti-HCV subject with an undetectable/negative hepatitis C RNA test can be enrolled

  27. Participation in another clinical study with any investigational medication or product administered within 28 days prior to first dose of study drug
  28. Female subjects who are pregnant or breast-feeding
  29. Subjects unable or unwilling to discontinue excluded medications for at least 2 weeks prior to first dose of study drug
  30. Other serious conditions, in the Investigator's opinion

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04073615


Contacts
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Contact: Steven Norton, PhD 8013037440 ext 275 steven.norton@elevartherapeutics.com

Locations
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United States, Florida
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: TBD TBD    615-524-4384    scott.ramsey@sarahcannon.com   
Principal Investigator: Manish Patel         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jesse Huffman    314-747-6268    jessehuffman@wustl.edu   
Principal Investigator: Nikolaos Trikalinos         
United States, Tennessee
Vanderbilt University School of Medicine Recruiting
Nashville, Tennessee, United States, 37232
Contact: Heather Barnes    615-936-3428    heather.barnes@vumc.org   
Principal Investigator: Jordan Berlin         
Sponsors and Collaborators
Elevar Therapeutics
Investigators
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Study Director: Steven Norton, PhD Elevar Therapeutics, Inc.
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Responsible Party: Elevar Therapeutics
ClinicalTrials.gov Identifier: NCT04073615    
Other Study ID Numbers: RM-110
First Posted: August 29, 2019    Key Record Dates
Last Update Posted: February 17, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Trifluridine
Apatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antiviral Agents
Anti-Infective Agents