Preoperative immunotherapy with atezolizumab (Tecentriq®) and tiragolumab in patients with colorectal liver metastases (CRLM) (the PURPLE trial)
- Conditions
- Therapeutic area: Diseases [C] - Neoplasms [C04]Colorectal liver metastases (CRLM)
- Registration Number
- CTIS2022-503044-40-00
- Lead Sponsor
- niversitaetsklinikum Essen AöR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 18
Male or female, 18 years of age or older on day of signing informed consent form, Negative human immunodeficiency virus (HIV) test at screening (see exclusion criterion 16 for exceptions), For patients with hepatitis B virus (HBV): HBV DNA < 500 IU/mL (or 2,500 copies/mL) at screening Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should be managed per institutional treatment guidelines. Patients receiving anti-viral medication must have initiated treatment for at least 2 weeks prior to randomization and should continue treatment for at least 6 months after the final dose of study treatment, Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening The HCV RNA test will be performed only for patients who have a positive HCV antibody test., For women of childbearing potential (WCBP): A woman is considered to be of childbearing potential if she is post-menarchal, has not reached a postmenopausal state (= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). • Should have a negative serum pregnancy test within 14 days prior to randomization. • Agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of <1% per year during the treatment period and for at least 5 months after last study drug administration. • Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices. • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception, For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined below: • Men with a female partner of childbearing potential or pregnant female partner: men must be sterilized or remain abstinent or use a condom during the treatment period and for 90 days after the last dose of tiragolumab to avoid exposing the embryo. • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence and withdrawal are not acceptable methods of contraception. • Men must refrain from donating sperm during this same period., Patient is willing and able to comply with the protocl for the duration of the study including undergoing treatment and scheduled visits and examinations, Signed informed consent, Histologically confirmed adenocarcinoma [mixed adenoneuroendocrine (MANEC) are alowed, if predominant part in adenocarcinoma] of the colon or rectum with liver metastases (CRLM)(synchronous or metachronous) that are amenable to surgical resection with curative intent based on the decision of the local multidisciplinary tumor board. Two stages resections of CRLM and primary tumor is allowed according to local guidelines., CRLM have to be accessible for biopsy, Microsatellite stable (MSS)/proficient mismatch repair (pMMR) disease (as
Evidence of metastases, except for liver and local lymph node metastases, History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation, Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab, Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment., Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX?) are allowed., Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN), Positive Epstein-Barr-Virus (EBV) viral capsid antigen IgM test at screening. An EBV polymerase chain reaction (PCR) test should be performed as clinically indicated to screen for acute infection or suspected chronic active infection., Presence of severe infection within 4 weeks prior to to randomization, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact patient safety, Positive human immunodeficiency virus (HIV) Known HIV+ patients may be included but must have: o A stable regimen of highly active anti-retroviral therapy (HAART) for at least 3 months o No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections o A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests, Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening, Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-TIGIT therapeutic antibodies, Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening followed by a negative HBV DNA test, are eligible for the study. The HBV DNA test will be performed only for patients who have a positive total HBcAb test., Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test, Active tuberculosis, Treatment with therapeutic oral or i.v. antibiotics within 2 weeks prior to randomization Exception: Prophylactic antibiotics (e.g., to prevent a urinary tract infection
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to estimate the pathological tumor response rate (Tumor regression grade (TRG) 1 and 2 according to Rubbia Brandt) on routine hematoxylin and eosin staining of resected tumors.;Secondary Objective: To assess the feasibility of the study design, defined as > 80% of patients (10 out of 12 in the experimental arms) who underwent surgery, To evaluate safety of preoperative short time immunotherapy and assessment of postoperative complication rates within 90 days of surgery, To assess resectability in patients with or without preoperative immunotherapy, To determine PET response in patients with or without preoperative short term IO therapy, To identify reasons for no surgery, To estimate pathological response rate according to Rubbia Brandt by independent central review;Primary end point(s): Percentage of resected patients with complete or major pathological regression
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Percentage of patients who underwent surgery after preoperative IO therapy;Secondary end point(s):Incidence, relatedness and severity of adverse events occurring during preoperative short time immunotherapy within 90 days of surgery (Severity for all events will be graded according to NCI CTCAE v5.0);Secondary end point(s):Assessment of postoperative complication rates according to the Clavien-Dindo Classification;Secondary end point(s):Mortality within 90 days of surgery;Secondary end point(s):Estimation of curative (R0) resection rate;Secondary end point(s):Assessment of PET response (PET-CT or PET-MRI) after short term immunotherapy;Secondary end point(s):Patients, who do not undergo surgery: Reasons for not having surgery;Secondary end point(s):Percentage of resected patients with complete or major pathological regression as evaluated by independent central review