Study of Supplemental Arginine With Chemotherapy and Immunotherapy in Platinum Resistant Ovarian, Fallopian Tube, and Peritoneal Cancer

August 14, 2026 updated by: Rebecca Arend

Phase I Study of Supplemental Arginine With Chemotherapy and Immunotherapy in Platinum Resistant Ovarian, Fallopian Tube, and Peritoneal Cancer

This is an open-label, Phase 1 clinical study to evaluate the safety, tolerability, PK profiles, and clinical activity of IV and PO arginine supplementation + SOC chemoimmunotherapy regimens in participants with PROC.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase I, investigator-initiated and open-label study. Patients will be evaluated and treated at University of Alabama Birmingham Hospital. Patients will receive both oral and IV arginine with the physician choice of paclitaxel, pembrolizumab, +/- bevacizumab or pembrolizumab, bevacizumab, and oral cyclophosphamide, where doses and schedule are consistent with standard of care. Patients who are excluded from the trial due to progression will be scheduled for three- and six-months follow-up evaluations after the last dose. The goal for enrollment will be 6-24 patients with a 3-patient safety dose escalation lead-in using a 3+3 enrollment model for each regimen.

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Rebecca C Arend, MD
  • Phone Number: (205) 934-4986
  • Email: rarend@uabmc.edu

Study Contact Backup

  • Name: Rebecca A Arend
  • Phone Number: 2059752257
  • Email: al2eli@uab.edu

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Womens & Infants Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Must be at least 18 years of age
  2. ECOG performance status of 0 or 1 (see Appendix A).

  3. Patient must be a candidate for either cohort A or cohort B treatment backbone.

    • For patients enrolling on treatment cohort A, PD-L1 positivity must be ≥1. Patient's with PD-L1 positivity ≥1% can enroll in cohort B at physician's discretion.
    • If PD-L1 positivity is unavailable or is <1%, patients can only enroll on treatment cohort B.
  4. Patients must have high-grade serous or endometrioid histology
  5. Recovery to baseline or ≤ Grade 1 CTCAE v.5.0 from toxicities related to the prior therapy, unless after discussion with the medical monitor the AE(s) are deemed clinically non-significant and/or stable on supportive therapy
  6. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

  7. Patients must have adequate hematologic, liver and kidney functions prior to lead-in chemotherapy defined as:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L (1,500/μL)
    2. Platelet count ≥ 100 x 109 /L (100,000/μL) without platelet transfusion in the prior 10 days
    3. Hemoglobin ≥ 9.0 g/dL
    4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
    6. Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN)
    7. Serum albumin ≥ 2 g/dL.

Exclusion Criteria:

  1. History of allergic reactions contributed to compounds of similar chemical or biological composition to R-Gene 10 or Arginaid.
  2. Patient unwilling/unable to receive daily arginine treatment (IV or oral)
  3. Patients with a history of serologically confirmed HSV-1 or HSV-2 outbreaks
  4. Receiving systemic corticosteroids or have severe comorbities where treatment with corticosteroids may be required.
  5. Actively treated auto-immune disease.
  6. Taking medications that interfere with the urea cycle such as valproate or xanthine oxidase inhibitors.
  7. Current intercurrent illnesses including active infection, symptomatic congestive heart failure, unstable angina, or cardiac arrhythmias.
  8. Patients with history of Peptic Ulcer Disease
  9. Contraindications to receive standard of care treatment backbone with either paclitaxel, bevacizumab, pembrolizumab, or cyclophosphamide.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CPS>1, physician's choice for Cohort A or Cohort B

Cohort A:

Cohort A1_Weekly paclitaxel + q3w pembrolizumab +/- bevacizumab + 4.5g daily oral arginine Cohort A2_Weekly paclitaxel + q3w pembrolizumab +/- bevacizumab + q3w 30g IV arginine Cohort A3_Weekly paclitaxel + q3w pembrolizumab +/- bevacizumab + q3w 30g IV arginine + 4.5g daily PO arginine A3 Expansion_Continue previous regimen

OR

Cohort B:

Cohort B1_q3w IV bevacizumab, q3w IV pembrolizumab, daily oral phosphamide, 4.5g daily oral arginine Cohort B2_q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine Cohort B3_q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine + 4.5g PO arginine B3 Expansion_ Continue previous regimen
Drug: Cohort A1
Weekly paclitaxel + q3w pembrolizumab +/- bevacizumab + 4.5g daily oral arginine
Other Names:
  • Pembrolizumab
  • bevacizumab
  • Paclitaxel
  • Oral Arginine (Arginaid®)
Drug: Cohort A2
Weekly paclitaxel + q3w pembrolizumab +/- bevacizumab + q3w 30g IV arginine
Other Names:
  • Pembrolizumab
  • bevacizumab
  • paclitaxel
  • IV Arginine (R-Gene® 10)
Drug: Cohort A3
Weekly paclitaxel + q3w pembrolizumab +/- bevacizumab + q3w 30g IV arginine + 4.5g daily PO arginine
Other Names:
  • Pembrolizumab
  • bevacizumab
  • paclitaxel
  • Oral Arginine (Arginaid®)
  • IV arginine
Drug: A3 Expansion
Continue - Weekly paclitaxel + q3w pembrolizumab +/- bevacizumab + q3w 30g IV arginine + 4.5g daily PO arginine
Other Names:
  • Pembrolizumab
  • bevacizumab
  • paclitaxel
  • Oral Arginine (Arginaid®)
  • IV arginine
Drug: Cohort B1
q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 4.5g daily oral arginine
Other Names:
  • Oral Arginine (Arginaid®)
  • IV bevacizumab
  • IV Pembrolizumab
  • oral phosphamide
Drug: Cohort B2
q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine
Other Names:
  • IV arginine
  • IV bevacizumab
  • oral phosphamide
  • IV pembrolizumab
Drug: Cohort B3
q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine + 4.5g PO arginine
Other Names:
  • Oral Arginine (Arginaid®)
  • IV arginine
  • IV bevacizumab
  • oral phosphamide
  • IV pembrolizumab
Drug: B3 Expansion
Continue - q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine + 4.5g PO arginine
Other Names:
  • Oral Arginine (Arginaid®)
  • IV arginine
  • IV bevacizumab
  • oral phosphamide
  • IV pembrolizumab
Experimental: CPS<1, must be assigned to Cohort B

Cohort B:

Cohort B1_q3w IV bevacizumab, q3w IV pembrolizumab, daily oral phosphamide, 4.5g daily oral arginine Cohort B2_q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine Cohort B3_q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine + 4.5g PO arginine B3 Expansion_ Continue previous regimen
Drug: Cohort B1
q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 4.5g daily oral arginine
Other Names:
  • Oral Arginine (Arginaid®)
  • IV bevacizumab
  • IV Pembrolizumab
  • oral phosphamide
Drug: Cohort B2
q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine
Other Names:
  • IV arginine
  • IV bevacizumab
  • oral phosphamide
  • IV pembrolizumab
Drug: Cohort B3
q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine + 4.5g PO arginine
Other Names:
  • Oral Arginine (Arginaid®)
  • IV arginine
  • IV bevacizumab
  • oral phosphamide
  • IV pembrolizumab
Drug: B3 Expansion
Continue - q3w IV bevacizumab + q3w IV pembrolizumab + daily oral phosphamide + 30mg IV arginine + 4.5g PO arginine
Other Names:
  • Oral Arginine (Arginaid®)
  • IV arginine
  • IV bevacizumab
  • oral phosphamide
  • IV pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with serious adverse events
Time Frame: Baseline through year 2
This measures the proportion of patients experiencing serious adverse events
Baseline through year 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: Baseline through year 2
Tumor burden will be evaluated in all participants by the investigator at screening and during/after the intervention period per RECIST 1.1 guidelines. Based on changes in tumor burden, participants will be classified as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). Participants who are classified as CR or PR will be defined as responders. The overall response rate (ORR) is the proportion of responders out of the evaluable participants. ORR = (PR + CR)/(PR + CR+ SD+ PD)
Baseline through year 2
Duration of Response
Time Frame: Baseline through year 2
Duration of response (DOR) is a time-to-event endpoint measured only in participants who respond to treatment. DOR is the time between response to treatment and disease progression or death. Patients who are lost to follow-up before disease progression or death are censored at time of last contact.
Baseline through year 2
Disease control rate
Time Frame: Baseline through year 2
Tumor burden will be evaluated in all participants by the investigator at screening and during/after the intervention period per RECIST 1.1 guidelines. Based on changes in tumor burden, participants will be classified as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). Participants who are classified as CR, PR or SD will be defined as having disease control. The disease control rate (DCR) is the proportion of participants with disease control out of the evaluable participants. DCR = (PR + CR + SD)/(PR + CR+ SD+ PD)
Baseline through year 2
Progression Free Survival
Time Frame: Baseline through year 2
Progression free survival (PFS) is a time-to-event endpoint. PFS is the time between start of treatment and the earlier of disease progression or death. Patients who are lost to follow-up before disease progression or death are censored at time of last contact.
Baseline through year 2
Overall Survival
Time Frame: Baseline through year 2
Overall survival (OS) is a time-to-event endpoint. OS is the time between start of treatment and death. Patients who are lost to follow-up before death are censored at time of last contact.
Baseline through year 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rebecca Arend

Investigators

  • Principal Investigator: Rebecca C Arend, MD, The University of Alabama at Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

January 1, 2029

Study Registration Dates

First Submitted

August 14, 2026

First Submitted That Met QC Criteria

August 14, 2026

First Posted (Actual)

August 19, 2026

Study Record Updates

Last Update Posted (Actual)

August 19, 2026

Last Update Submitted That Met QC Criteria

August 14, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-300016887 (UAB 2667)
  • O'Neal Cancer Center (Other Identifier: O'Neal Comprehensive Cancer Center at UAB)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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