AzTrials
AzTrials

CCR5Phase 2NCT05730673

Leronlimab in Combination With Regorafenib in Patients With CCR5+, Metastatic Colorectal Cancer

A Phase 2 study testing 700mg leronlimab weekly dose, 80mg Regorafenib at week 1 and 120mg Regorafenib at week2 in people with CCR5 and Microsatellite Stable, run by CytoDyn, Inc..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

This is aPhase II Study of Leronlimab (PRO 140) in combination with Regorafenib in Patients with CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
CCR5, Microsatellite Stable, Metastatic
What is being tested?
700mg leronlimab weekly dose, 80mg Regorafenib at week 1 and 120mg Regorafenib at week2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
20 Sep 2022to 10 Aug 2023
Phase
Phase 2
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

  • Male or female patient age ≥ 18 years with a history of treated colorectal cancer with unresectable metastases of the primary colorectal cancer to the other organs.
  • Demonstrate CCR5 + by IHC (>10% membranous staining completed at the reference laboratory of Dr. Hallgeir Rui at Medical College of Wisconsin).
  • Note: This test will be done as part of the pre-screening period. It will be performed in archival metastatic tissue.
  • Histologically confirmed for microsatellite stable MSS colorectal cancer by Immunohistochemistry (IHC) or Next-generation sequencing (NGS)
  • Metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, VEGF antibody, and, if RAS wild-type, an anti-EGFR therapy Note: Prior Regorafenib therapy is not allowed.
  • Have measurable disease per RECIST 1.1
Show all 22Show fewer
  • Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Expected survival of at least three months
  • No chemotherapy treatment within the last four weeks or less than wash out period of the chemotherapy agents, whichever is shorter
  • Patients must have adequate organ and bone marrow function within 28 days prior to registration, as defined below:
  • Leukocytes ≥ 3,000/mcL;
  • Absolute neutrophil count ≥ 1,500/mcL;
  • Platelet count > 75,000/mm^3
  • Total bilirubin: within normal institutional limits;
  • AST(SGOT) \&ALT(SPGT) ≤ 2.5 X institutional upper limit of normal (ULN) (applicable to all patients, irrespective of liver disease or metastasis); and
  • Creatinine: within normal institutional limits.
  • Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
  • Both male and female patients and their partners of childbearing potential must agree to use two medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or one of the following methods of birth control (intrauterine devices, tubal sterilization or vasectomy) or must practice complete abstinence from intercourse of reproductive potential from study entry to 6 months after the last day of treatment (excluding women who are not of childbearing potential and men who have been sterilized).
  • Females of child-bearing potential (FOCBP) must have a negative serum pregnancy test at Screening Visit and negative urine pregnancy test prior to receiving the first dose of study drug; and
  • Male participants must agree to use contraception and refrain from donating sperm for at least 120 days after the last dose of study intervention.
  • Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.

Who cannot join

  • Inability to understand the aims of the study and/or protocol procedures
  • Hypersensitivity towards Regorafenib or Leronlimab (PRO 140).
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to humanized monoclonal antibodies
  • Any other concurrent antineoplastic treatment including irradiation (local radiation of single non-target lesions for palliation only allowed)
  • Any condition requiring continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks prior to first dose of study treatment. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
  • Clinically significant active coronary heart disease and cardiovascular insufficiency with hypotension (systolic blood pressure <100 mmHg) per PI discretion.
Show all 25Show fewer
  • Cardiac arrhythmias requiring anti-arrhythmic therapy; Note: pace makers, beta blockers, or digoxin are permitted
  • Any GI or Respiratory system disorders that per PI discretion can interfere with the study treatment or jeopardize the patient's health.
  • Prior allogeneic bone marrow transplantation
  • Administration of a live, attenuated vaccine within four weeks prior to start of maintenance treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Positive test for human immunodeficiency virus (HIV) or HIV infection
  • Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test) or hepatitis C. Note: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible.
  • Active or latent tuberculosis
  • Clinically active brain metastases, defined as untreated symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
  • Patient who have an active infection requiring systemic therapy.
  • Patient who are taking strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) or strong CYP3A4 inhibitors (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and voriconazole)
  • Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 120 days after the last dose of study intervention.
  • Have undergone major surgery and have not recovered adequately from any toxicity and/or complications from the intervention before starting study intervention.
  • Have a seizure disorder requiring ongoing antiseizure therapy or with any condition that, in the judgment of the investigator, is likely to increase the risk of seizure (e.g., CNS malignancy.)
  • Have received prior therapy with Leronlimab or any other CCR5 antagonist (e.g., maraviroc).
  • Have received prior therapy with regrafenib.
  • Have been treated with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137).
  • Patient who received prior radiotherapy (not to target lesions) within 3 weeks of start of study intervention.
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days prior to enrollment;
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

About this study

Official title: A Phase II Study of Leronlimab (PRO 140) in Combination With Regorafenib in Patients With CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC)

This is aPhase II Study of Leronlimab (PRO 140) in combination with Regorafenib in Patients with CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC)

Read the detailed description

This ia a phase II, single arm study with 30 patients in order to test the hypothesis that the combination of Leronlimab (PRO 140) SC and oral Regorafenib will increase PFS in patients with CCR5 + MSS mCRC.

Leronlimab will be administered subcutaneously at a weekly dose of 700 mg in combination with staring dose of 80 mg Regorafenib at first week of the Cycle 1, followed by escalation of Regorafenib dose to 120 mg and 160 mg in second and third weeks of Cycle 1, respectively. No Regorafenib will be administered during the fourth week.

Being tested
700mg leronlimab weekly dose, 80mg Regorafenib at week 1, 120mg Regorafenib at week2, 160 mg Regorafenib at week 3
Keywords
Metastatic, Colorectal Cancer
Medical subject headings
Neoplasm Metastasis, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 700mg leronlimab weekly doseDrug

    leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5

  • 80mg Regorafenib at week 1Drug

    Regorafenib is a small-molecule multiple kinase inhibitor

  • 120mg Regorafenib at week2Drug

    Regorafenib is a small-molecule multiple kinase inhibitor

  • 160 mg Regorafenib at week 3Drug

    Regorafenib is a small-molecule multiple kinase inhibitor

Study groups in NCT05730673
Study groupRoleWhat they receive
Leronlimab in combinatiob with RegorafenibExperimentalLeronlimab (PRO 140) will be administered subcutaneously at a weekly dose of 700 mg in combination with staring dose of 80 mg Regorafenib at first week of the Cycle 1, followed by escalation of Regorafenib dose to 120 mg and 160 mg in second and third weeks of Cycle 1, respectively. No Regorafenib will be administered during the fourth week.
Receives: Drug: 700mg leronlimab weekly dose; Drug: 80mg Regorafenib at week 1; Drug: 120mg Regorafenib at week2; Drug: 160 mg Regorafenib at week 3

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR, defined as Complete Response (CR) + Partial Response (PR)) in subjects with CCR5+ mCRC treated with Leronlimab (PRO 140) and Regorafenib.

    Measured: Four weeks

Secondary outcomes (5)

  1. The number, frequency, and severity of adverse events (AEs) collected from the time of first treatment until 12 weeks after study treatment completion to evaluate safety of Leronlimab (PRO 140) and Regorafenib in subjects with CCR5+ mCRC.

    Measured: Four weeks

  2. Progression free survival (PFS) defined as time in months from the date of first study treatment to the date of disease progression or death from any cause, whichever comes first.

    Measured: Four weeks

  3. Overall survival defined as time in months from the date of first study treatment to the date of death;

    Measured: Four weeks

  4. Time to new metastases (TTNM)

    Measured: Four weeks

  5. The change from baseline in circulating tumor cells (CTC) in the peripheral blood.

    Measured: Four weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2023
  2. Study start20 Sep 2022 (estimated)
  3. Primary completion27 May 2023 (estimated)
  4. Study completion10 Aug 2023 (estimated)

Why it stopped: No participants enrolled

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05730673
Sponsor's protocol ID
CD08_mCRC
Status last verified
Feb 2023
First submitted
7 Feb 2023
Last updated
17 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 700mg leronlimab weekly dose, 80mg Regorafenib at week 1 and 120mg Regorafenib at week2 in people with CCR5 and Microsatellite Stable, run by CytoDyn, Inc..

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 22 inclusion and 25 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: withdrawn, as of the sponsor's last update on 17 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 withdrawn before enrolling participants, so there are no results.

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?

Overall response rate (ORR, defined as Complete Response (CR) + Partial Response (PR)) in subjects with CCR5+ mCRC treated with Leronlimab (PRO 140) and Regorafenib. (time frame: Four weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05730673.

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 17 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in