A Study of Immunotherapy Drugs Nivolumab and Ipilimumab in Patients w/Resectable Malignant Peritoneal Mesothelioma

Mesothelioma Clinical Trial

Official title:

A Phase II Prospective, Open-label Trial of Perioperative Combination Nivolumab and Ipilimumab in Patients With Resectable Malignant Peritoneal Mesothelioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05041062
• Other study ID #: IRB21-0672
• Status: Completed
• Phase: Phase 2
• Start date: December 1, 2021
• Est. completion date: April 13, 2023

Study information

• Verified date: December 2023
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is for individuals who have peritoneal mesothelioma, a cancer of the lining of your abdominal wall and organs (the peritoneum). Doctors leading the study would like to determine the effects of treating this cancer with immunotherapy drugs (nivolumab and ipilimumab - the two study drugs that will be used in this study) before and after surgery. Doctors hope to learn if giving these two drugs before surgery will decrease the amount of viable (live) cancer cells that remain at the time of surgery and whether it will delay the time it could take for the cancer to regrow.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: April 13, 2023
• Est. primary completion date: April 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Have a diagnosis of histologically or cytologically confirmed peritoneal mesothelioma, of epithelial, biphasic, or sarcomatoid subtypes

2. Have disease burden amenable to cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC), as determined by a surgeon specializing in mesothelioma

3. Have measurable or evaluable disease based on RECIST 1.1 or on laparoscopy

4. Have no definitive evidence of visceral metastases by best staging

5. Be willing to undergo laparoscopy or mini-laparotomy for peritoneal staging

6. Adequate organ function as determined by screening labs,

7. Have an ECOG performance status of < 2

8. Be 18 years of age on day of signing informed consent

9. Be willing and able to provide written informed consent for the trial

Exclusion Criteria:

1. Is currently participating in a study of an investigational agent and received an investigational agent within 4 weeks of the first dose of treatment on this protocol

2. Has received any immunotherapy agents outside of this protocol within 4 weeks of the first dose of treatment on this protocol

3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (>10 mg of prednisone daily or equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug.

4. Has a known history of active TB infection (Bacillus tuberculosis)

5. Has active COVID-19 infection

6. Has known history of, or any evidence of active, non-infectious pneumonitis that required steroids, or active pneumonitis

7. Has a severe hypersensitivity to nivolumab or any of its excipients

8. Has a severe hypersensitivity to ipilimumab or any of its excipients

9. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)

10. Has a known additional malignancy that is progressing or required active treatment within the 3 years prior to enrollment - exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or other tumors that will not affect life expectancy

11. Has an active infection requiring systemic therapy

12. Has a known history of HIV, Hepatitis B, or Hepatitis C

13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment

1. Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

2. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.8.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.

3. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

15. Is on anticoagulation that cannot be discontinued in the perioperative period

16. Has received a live vaccine within 30 days of planned start of study therapy

Related Conditions & MeSH terms

• Mesothelioma
• Mesothelioma, Malignant
• Peritoneal Mesothelioma

Intervention

Drug:
• Nivolumab
Nivolumab is an immunotherapy drug (a type of drug that helps your immune system fight cancer) that is often used with ipilimumab as the first treatment in adults with mesothelioma whose disease cannot be removed by surgery. The drug will be given as an IV infusion.
• Ipilimumab
Ipilimumab is a type of immunotherapy drug known as a checkpoint inhibitor, which helps your own immune system attack cancer cells.

Locations

Country	Name	City	State
United States	The University of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Pathologic (Disease) Response of Tumor to Nivolumab Combined With Ipilimumab Before Surgery	The response of participant's tumor to treatment with nivolumab and ipilimumab before surgery by analyzing tissue samples collected from participant during surgery for the presence of cancerous tumour cells. Major pathologic response will be defined as tissue samples containing less than or equal to 10% of residual (leftover) tumor/cancer in the tissue after surgery.	24 months
Secondary	Rate of Participants Who Report Serious Side Effects to Nivolumab Combined With Ipilimumab Before Surgery (Neoadjuvant Treatment)	The rate of participants who report Grade 3 or 4 serious adverse events (side effects) after taking nivolumab combined with ipilimumab before surgery. These side effects will be measured according to Common Terminology Criteria for Adverse Events v5.0 for up to 30 days after surgery.	3 weeks (timeframe for surgery ) + 30 days (timeframe for assessing side effects after surgery)
Secondary	Number of Participants Who Proceed to Surgery Without Delays After Receiving Nivolumab Combined With Ipilimumab	Number of participants who complete treatment with nivolumab and ipilimumab before surgery and proceed to surgery without extended treatment-related delays or progression precluding surgery as assessed by clinical /study records.	19 weeks
Secondary	Overall Survival of Participants Who Take Nivolumab Combined With Ipilimumab Before Surgery	Overall survival of participants who receive neoadjuvant nivolumab combined with ipilimumab, defined as time from enrollment on study to death from any cause.	42 Months
Secondary	Progression-Free Survival of Participants Who Take Nivolumab Combined With Ipilimumab Before Surgery	Progression-free survival of participants who receive neoadjuvant nivolumab combined with ipilimumab, defined as time from enrollment on study to death from any cause.	42 months
Secondary	Rate of Participants Who Report Serious Side Effects to Taking Nivolumab Combined With Ipilimumab After Surgery (Adjuvant Treatment)	The rate of participants who report Grade 3 or 4 serious adverse events (side effects) after taking nivolumab combined with ipilimumab after surgery. These side effects will be measured according to Common Terminology Criteria for Adverse Events v5.0.	12 weeks
Secondary	Radiologic Response to Nivolumab and Ipilimumab Before Surgery	Radiologic response to nivolumab and ipilimumab before surgery using radiology images of tumor pre- and post-treatment.	24 months
Secondary	Peritoneal Carcinomatosis Index (PCI) of Participants Who Taking Nivolumab Combined With Ipilimumab Before Surgery	The effect of nivolumab and ipilimumab on participant's tumor as assessed by a peritoneal carcinomatosis index (PCI) score, a score determined based on the size of participant's tumor after abdominal surgery.; The Peritoneal Cancer Index (PCI) scoring system is a diagnostic and prognostic tool. The PCI score is calculated by dividing the peritoneal (abdominal) cavity into 13 regions and assigning a score to each of the 13 regions. Each region receives a score of 0-3 based on the largest tumor size in each region. The total sum of all 13 regions is the PCI score. PCI scores can range from 0 to 39. Higher scores indicate more widespread and/or larger tumors in the peritoneal cavity.	12 weeks