Combining chemotherapy, radiation, and immunotherapy for advanced pancreatic cancer

Maintenance Ipilimumab + Nivolumab Post Induction Chemotherapy + SBRT for First Line

This study is testing a new treatment plan that combines chemotherapy, radiation, and immunotherapy to see if it can help people with advanced pancreatic cancer live longer and feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sheba Medical Center (Government)
• Drugs / interventions: chemotherapy, radiation, prednisone, ipililumab, nivolumab, immunotherapy, ipilimumab, ivolumab
• Locations: 1 site (Ramat Gan)
• Trial ID: NCT05088889 on ClinicalTrials.gov

What this trial studies

This study evaluates a novel treatment approach for stage IV pancreatic cancer, involving initial chemotherapy followed by stereotactic body radiation therapy (SBRT) and maintenance immunotherapy with ipilimumab and nivolumab. Patients will receive chemotherapy for at least four cycles, and those who do not progress will undergo SBRT before starting immunotherapy. The goal is to enhance the anti-tumor response by combining these modalities, with assessments for treatment efficacy occurring after eight weeks. This single-arm study aims to improve overall survival and progression-free survival in this challenging cancer population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with metastatic pancreatic adenocarcinoma who have not progressed after initial chemotherapy.

Not a fit: Patients with rapidly progressing disease or those who have previously received extensive treatment for pancreatic cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates and quality of life for patients with advanced pancreatic cancer.

How similar studies have performed: While combining immunotherapy with radiation is a novel approach in pancreatic cancer, similar strategies have shown promise in other cancers, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Provide written informed consent and be between the ages of 18 and up.
* Metastatic histology proven adenocarcinoma of the pancreas. If patient has primary resected tumor, tumor recurrence needs to \>12 months after last adjuvant chemotherapy.
* ECOG performance status 0-1.
* Life expectancy of \>= 3 months.
* If female and of child-bearing potential, have a negative serum pregnancy test during screening.
* Agree to use of a barrier method of contraception if sexually active (both men and women) from the time of administration of the first treatment and for at least 5 months after treatment.
* Have PT - INR \< 1.5, WBC \> 2000/μL absolute neutrophil count (ANC) \> 1500 x 103 cells/ μL, platelets ≥ 100,000/ μL, and hemoglobin \>= 9 mg/dL Serum creatinine \< 1.5 x ULN, unless creatinine clearance ≥ 40 mL/min (measured or calculated using the Cockroft-Gault formula) AST/ALT: \< 3.0 x ULN Total bilirubin \< 1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of \< 3.0x ULN).
* A disease lesion, including primary pancreas lung/liver/peritoneal/bone /lynph nodes, that is suitable for SBRT as deemed by the investigator.
* Screening procedures completed within 4 weeks of starting treatment.
* Availability of at least 1 measurable lesion not previously irradiated that is not planned to be irradiated with SBRT during the study and measurable as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
* Patient received minimum of 4 cycles of first-line chemotherapy of induction chemotherapy per investigator's decision without progression.
* Adjuvant treatment is allowed if ≥ 12 months has passed since last adjuvant treatment.
* Fresh biopsy specimens are required unless biopsy deemed unsafe by investigator.

Exclusion Criteria:

* Clinically significant pancreatitis within 8 weeks of treatment.
* Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 5 months after the study are excluded.
* A medical condition or any intercurrent medical illness or other medical condition that would in the judgment of the investigator compromise patient safety or the objectives of the study.
* Have participated in any therapeutic research study within the last 4 weeks.
* Known medical condition that predisposes to radiation toxicity (e.g. scleroderma)
* Has a known MSI-H phenotype or a known MMR deficiency.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
* Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with type I diabetes mellitus, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects that require intermittent use of bronchodilators or local steroids, e.g., inhaled or topical steroids, at a dose of less than the equivalent of 10mg prednisone daily, would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
* Has evidence of interstitial lung disease or active, non-infectious pneumonitis
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
* Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
* Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial (chronic pain management medications should not exclude study participation).

Where this trial is running

Ramat Gan

• Sheba Medical Centre — Ramat Gan, Israel (Recruiting)

Study contacts

• Principal investigator: Talia Golan, Prof. — Shaba Medical Center
• Study coordinator: Talia Golan, Prof.

Conditions Stage IV Pancreatic Cancer; Pancreatic adenocarcinoma; SBRT; immunotherapy; RECIST1.1