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Oregovomab and PLD in PARP Inhibitor Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment

Primary Purpose

PARP Inhibitor Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment

Status
Recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Orevogomab+PLD
Orevogomab+Paclitaxel
Sponsored by
Yonsei University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PARP Inhibitor Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment focused on measuring PARP inhibitor Resistant, platinum resistant

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adults 20 years old or older.
  2. Subjects with histologically confirmed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin
  3. Eligible histologic epithelial cell types: high grade serous adenocarcinoma, high grade endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, , and low-grade adenocarcinoma, or adenocarcinoma not otherwise specified (N.O.S.). [only up to 5 patients with non-high grade serous carcinoma will be included]
  4. Prior PARP inhibitor exposure (progressed through a prior PARP inhibitor)
  5. CA-125 ≥ 50 U/ml
  6. Prior platinum-based chemotherapy.
  7. Cohort 1 : 1-3 prior lines of therapies / Cohort 2 : Previous treatments of the 4 th line or more
  8. Not eligible for platinum re-treatment (prior allergic reaction or residual toxicity, patients who are not able to receive (in the physician's opinion) or willing to receive platinum treatment and platinum resistant patients)
  9. Received prior bevacizumab or not eligible for bevacizumab due to medical
  10. Adequate bone marrow function:

    • a. Absolute neutrophil count (ANC) ≥ 1,500/μL
    • b. Platelets ≥ 100,000/μL
    • c. Hemoglobin ≥ 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before first dose of study treatment).
  11. Adequate liver function:

    • a. Bilirubin < 1.5 times upper limit normal (ULN)
    • b. Lactate Dehydrogenase (LDH), SGOT/AST and SGPT/ALT < 2.5 times ULN
  12. Adequate renal function: a. Creatinine ≤ 1.5 times ULN
  13. ECOG Performance Status of 0 or 1.
  14. For women of childbearing potential, must be willing to avoid pregnancy by using a highly effective method of contraception from the first dose of study treatment to 60 days after last dose of study treatment.
  15. Sign informed consent and authorization permitting release of personal health information.

Exclusion Criteria:

  1. Participant has mucinous, germ cell, or borderline tumor of the ovary
  2. Female subjects who are lactating and breastfeeding, or have a positive serum pregnancy test within 7 days prior to the first dose of study treatment
  3. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  4. Active autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), or ankylosing spondylitis requiring active disease modifying treatment.
  5. Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab and PLD.
  6. Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc.
  7. Chronic therapeutic corticosteroid use, defined as > 5 days of prednisone or equivalent, with the exception of inhalers or those on a pre-planned steroid taper.
  8. Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia.
  9. Clinically significant active infection(s) at the time of screening.
  10. Any of the following conditions (on-study testing is not required):

    • a. Known HIV-infected subjects unless on effective anti-retroviral therapy with an undetectable viral load within 6 months, or
    • b. Known or suspected hepatitis B if active infection (patients with chronic hepatitis B infection must have an undetectable HBV viral load on suppressive therapy, if indicated; positive surface antibody alone is not an exclusion), or
    • c. Known or suspected hepatitis C infection which has not been treated and cured unless currently on treatment with an undetectable viral load).
  11. Uncontrolled or life-threatening diseases compromising safety evaluation.
  12. Participant has a known additional malignancy that is progressing or has required active treatment within the past 2 years Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ, endometrial carcinoma) that have undergone potentially curative therapy are not excluded.

    Note: Participants with synchronous primary endometrial cancer or a past history of primary endometrial cancer that met the following conditions are not excluded: Stage not greater than IA: no more than superficial myometrial invasion.

  13. Contraindications to the use of pressor agents
  14. Undergone more than one surgical debulking or have not recovered from surgery.
  15. History or evidence upon physical examination of CNS disease, seizures not controlled with standard medical therapy, or any brain metastases.
  16. Any of the following cardiovascular conditions:

    • a. Acute myocardial infarction within 6 months before the first dose of study treatment.
    • b. Current history of New York Heart Association (NYHA) Class III or IV heart failure (see Appendix H).
    • c. Evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic clinically significant findings.
  17. Unable to read or understand or unable to sign the necessary written consent before starting treatment
  18. Inability to attend or comply with treatment of follow-up scheduling

Sites / Locations

  • Yonsei University Health System, Severance HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1(1-3 prior line of chemotherapy)

Cohort2 (>3prior line of chemotherapy)

Arm Description

Oregovomab and PLD is synergistic in PARPi-resistant recurrent ovarian cancer.

Oregovomab and Paclitaxel show synergistic in PARPi-resistant recurrent ovarian cancer.

Outcomes

Primary Outcome Measures

Confirmed ORR
based on radiographically confirmed response according to CR+PR rate based on RECIST v1.1 as determined by the investigator

Secondary Outcome Measures

progression-free survival
PFS is calculated as the interval in months from the date of enrollment to the date of disease progression or the date of death, whichever comes first.
Overall survival (OS)
Overall survival (OS) will be calculated using the date of death OS is calculated as the interval in months from the date of enrollment to the date of death.
Time to first Subsequent Therapy
TFST, defined as time from the date of enrollment into the study to second anti-cancer therapy start date following study treatment completion, treatment exit [EOT] or death, will be determined.
Time to Second Subsequent Therapy
TSST, defined as time from the date of enrollment into the study to third anti-cancer therapy start date following study treatment completion, treatment exit [EOT] or death, will be determined.
Duration of response
DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
second objective disease progression
PFS2, defined as the time from enrollment into the study to the earlier date of progression on next-line therapy or death from any cause, will be determined.

Full Information

First Posted
June 1, 2022
Last Updated
May 22, 2023
Sponsor
Yonsei University
Collaborators
CanariaBio Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05407584
Brief Title
Oregovomab and PLD in PARP Inhibitor Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment
Official Title
Oregovomab and Non-platinum Chemotherapy in PARP Inhibitor Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment: a Multicenter, Two-cohort, Single-arm Phase 2 Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2022 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University
Collaborators
CanariaBio Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is phase II, open label, clinical trial to determine the efficacy of Oregovomab and non-platinum chemotherapy in PARP inhibitor resistant ovarian, fallopian tube, or primary peritoneal cancer patients who were not suitable for platinum retreatment. Patients who have received one to three prior lines of chemotherapy are to be assigned to Cohort 1 (oregovamab 2 mg [C1,2,3,5,7 for five doses] + pegylated liposomal doxorubicin [PLD] 40 mg/m2 q4w, n=28), while patients who have received more than three prior lines of chemotherapy are to be assigned to Cohort 2 (oregovamab 2 mg [C1,2,3,5,7 for five doses] + weekly paclitaxel 80 mg/m2 [D1,8,15 q4w], n=28). A total of 56 patients will be recruited and treated with oregovomab + PLD / weekly paclitaxel until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint is objective response rate by RECIST 1.1.
Detailed Description
This study is a two-cohort, single arm phase II study in patients with PARP inhibitor-resistant ovarian, fallopian tube, or primary peritoneal cancer. The efficacy and safety of five administrations of Oregovomab 2mg IV in combination with non-platinum chemotherapy will be evaluated with recurrent ovarian cancer who have progressed with prior PARP inhibitor treatment. Patients with disease under study will be screened for eligibility during the period 28 days immediately prior to starting study drug on Day 1. Laboratory and radiological assessments performed as part of standard of care before signing informed consent may be used if performed within the screening/baseline time window. During this time, the inclusion and exclusion criteria will be assessed and all screening assessments, laboratory tests, and procedures will be performed. Cohort 1(1-3 prior line of chemotherapy) PLD (40 mg / m2 IV over three hours in one day) to be repeated till progression or unacceptable toxicity every four weeks (28 days) Investigational agent (Oregovomab): 2 mg diluted in 50 mL saline for injection administered IV following PLD over approximately 20 (acceptable range 15-30) minutes for a total of 5 scheduled injections, one each at Cycle 1, Cycle 2, Cycle 3, Cycle 5, and Cycle 7 Cohort2 (>3prior line of chemotherapy) paclitaxel (80 mg / m2 IV over three hours in one day) to be repeated till progression or unacceptable toxicity every four weeks on day 1, 8, 15 Investigational agent (Oregovomab): 2 mg diluted in 50 mL saline for injection administered IV following paclitaxel over approximately 20 (acceptable range 15-30) minutes for a total of 5 scheduled injections, one each at Cycle 1, Cycle 2, Cycle 3, Cycle 5, and Cycle 7

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PARP Inhibitor Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment
Keywords
PARP inhibitor Resistant, platinum resistant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
56 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1(1-3 prior line of chemotherapy)
Arm Type
Experimental
Arm Description
Oregovomab and PLD is synergistic in PARPi-resistant recurrent ovarian cancer.
Arm Title
Cohort2 (>3prior line of chemotherapy)
Arm Type
Experimental
Arm Description
Oregovomab and Paclitaxel show synergistic in PARPi-resistant recurrent ovarian cancer.
Intervention Type
Drug
Intervention Name(s)
Orevogomab+PLD
Intervention Description
PLD (40 mg / m2 IV over three hours in one day) to be repeated till progression or unacceptable toxicity every four weeks (28 days) Investigational agent (Oregovomab): 2 mg diluted in 50 mL saline for injection administered IV following PLD over approximately 20 (acceptable range 15-30) minutes for a total of 5 scheduled injections, one each at Cycle 1, Cycle 2, Cycle 3, Cycle 5, and Cycle 7
Intervention Type
Drug
Intervention Name(s)
Orevogomab+Paclitaxel
Intervention Description
paclitaxel (80 mg / m2 IV over three hours in one day) to be repeated till progression or unacceptable toxicity every four weeks on day 1, 8, 15 Investigational agent (Oregovomab): 2 mg diluted in 50 mL saline for injection administered IV following paclitaxel over approximately 20 (acceptable range 15-30) minutes for a total of 5 scheduled injections, one each at Cycle 1, Cycle 2, Cycle 3, Cycle 5, and Cycle 7
Primary Outcome Measure Information:
Title
Confirmed ORR
Description
based on radiographically confirmed response according to CR+PR rate based on RECIST v1.1 as determined by the investigator
Time Frame
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary Outcome Measure Information:
Title
progression-free survival
Description
PFS is calculated as the interval in months from the date of enrollment to the date of disease progression or the date of death, whichever comes first.
Time Frame
Up to 1 years
Title
Overall survival (OS)
Description
Overall survival (OS) will be calculated using the date of death OS is calculated as the interval in months from the date of enrollment to the date of death.
Time Frame
Up to 1 years
Title
Time to first Subsequent Therapy
Description
TFST, defined as time from the date of enrollment into the study to second anti-cancer therapy start date following study treatment completion, treatment exit [EOT] or death, will be determined.
Time Frame
The date of first documented first subsequent treatment or date of death, assessed up to 72 months
Title
Time to Second Subsequent Therapy
Description
TSST, defined as time from the date of enrollment into the study to third anti-cancer therapy start date following study treatment completion, treatment exit [EOT] or death, will be determined.
Time Frame
The date of first documented second subsequent treatment assessed up to 72 months
Title
Duration of response
Description
DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
Time Frame
Up to 1 years
Title
second objective disease progression
Description
PFS2, defined as the time from enrollment into the study to the earlier date of progression on next-line therapy or death from any cause, will be determined.
Time Frame
Up to 1 years

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
female
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adults 20 years old or older. Subjects with histologically confirmed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin. Eligible histologic epithelial cell types: high grade serous adenocarcinoma, high grade endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, , and low-grade adenocarcinoma, or adenocarcinoma not otherwise specified (N.O.S.). [only up to 5 patients with non-high grade serous carcinoma will be included] Prior PARP inhibitor exposure (progressed through a prior PARP inhibitor) CA-125 ≥ 50 U/ml Prior platinum-based chemotherapy. Cohort 1 : 1-3 prior lines of therapies / Cohort 2 : Previous treatments of the 4th line or more. Not eligible for platinum re-treatment (prior allergic reaction or residual toxicity, patients who are not able to receive (in the physician's opinion) or willing to receive platinum treatment and platinum resistant patients) Received prior bevacizumab or not eligible for bevacizumab due to medical. Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1,500/μL Platelets ≥ 100,000/μL Hemoglobin ≥ 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before first dose of study treatment). Adequate liver function: Bilirubin < 1.5 times upper limit normal (ULN) Lactate Dehydrogenase (LDH), SGOT/AST and SGPT/ALT < 2.5 times ULN Adequate renal function: a. Creatinine ≤ 1.5 times ULN ECOG Performance Status of 0 or 1. For women of childbearing potential, must be willing to avoid pregnancy by using a highly effective method of contraception from the first dose of study treatment to 60 days after last dose of study treatment. Sign informed consent and authorization permitting release of personal health information. Exclusion Criteria: Participant has mucinous, germ cell, or borderline tumor of the ovary. Female subjects who are lactating and breastfeeding, or have a positive serum pregnancy test within 7 days prior to the first dose of study treatment. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. Active autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), or ankylosing spondylitis requiring active disease modifying treatment. Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab and PLD. Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc. Chronic therapeutic corticosteroid use, defined as > 5 days of prednisone or equivalent, with the exception of inhalers or those on a pre-planned steroid taper. Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia. Clinically significant active infection(s) at the time of screening. Any of the following conditions (on-study testing is not required): Known HIV-infected subjects unless on effective anti-retroviral therapy with an undetectable viral load within 6 months, or Known or suspected hepatitis B if active infection (patients with chronic hepatitis B infection must have an undetectable HBV viral load on suppressive therapy, if indicated; positive surface antibody alone is not an exclusion), or Known or suspected hepatitis C infection which has not been treated and cured unless currently on treatment with an undetectable viral load). Uncontrolled or life-threatening diseases compromising safety evaluation. Participant has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ, endometrial carcinoma) that have undergone potentially curative therapy are not excluded. Note: Participants with synchronous primary endometrial cancer or a past history of primary endometrial cancer that met the following conditions are not excluded: Stage not greater than IA: no more than superficial myometrial invasion. Contraindications to the use of pressor agents History or evidence upon physical examination of CNS disease, seizures not controlled with standard medical therapy, or any brain metastases. Any of the following cardiovascular conditions: Acute myocardial infarction within 6 months before the first dose of study treatment. Current history of New York Heart Association (NYHA) Class III or IV heart failure (see Appendix H). Evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic clinically significant findings. Unable to read or understand or unable to sign the necessary written consent before starting treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jung-Yun Lee
Phone
82-2-2228-2237
Email
jungyunlee@yuhs.ac
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jung-Yun Lee
Organizational Affiliation
Severance Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yonsei University Health System, Severance Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jung-Yun Lee
Phone
+82-2-2228-2237
Email
jungyunlee@yuhs.ac

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Oregovomab and PLD in PARP Inhibitor Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment

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