Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Study treatments include SBRT (Stereotactic radiation therapy) to one primary/metastatic tumor (3 fractions of 8Gy) , and ipilimumab (1mg/kg every six weeks) + nivolumab (360mg every three weeks) .

Every 8 weeks patients will be assessed for response; responders will continue ipilimumab + nivolumab until disease progression, non-responders will receive very low dose radiation (2Gy single fraction to metastatic lesions of choice) prior to continuing ipilimumab + nivolumab .

Nivolumab administered IV over 30 minutes at a dose of 360mg every 3 weeks

Ipilimumab administered IV over 30 minutes at 1 mg/kg every 6 weeks

ipilimumab

Three fractions of 8 Gy, treated on alternate days

Stereotactic body radiation therapy

a single fraction of 2Gy will be given to the metastatic lesions at first progression

Low dose irradiation

Talia Golan, Prof.

Tali Aviv

Talia Golan, MD

aliza ackerstein, Msc

In this study we aim to test the efficacy of a combined and novel approach including induction chemotherapy (per standard of care) followed by SBRT and maintenance ipililumab + nivolumab in the first line setting of stage IV PDAC.

Study Hypothesis:

Cytotoxic chemotherapy followed by hypofractionated radiotherapy will sensitize pancreatic cancer to immunotherapy consisting of combined PD-1 and CTLA4 blockade. We hypothesize that direct targeting of the pancreatic cancer cells by chemotherapy and hypofractionated radiotherapy is necessary for initial anti-tumor response. Furthermore, the combination of immunotherapy as a maintenance strategy will have profound anti-tumor efficacy in this setting.

Implications of hypothesis:

* Improved response rate above historical controls
* Lengthened progression-free survival
* Improved overall-survival

Exploratory Hypothesis:

We hypothesize that baseline markers of immune activation such as Tumor Infiltrating Lymphocytes and CD8+ lymphocytes will correlate with response to ipililumab + nivolumab and that responders will have distinct tumor immune phenotype as determined by immunohistochemistry and gene expression profiling compared to nonresponders.

Maintenance Ipilimumab + Nivolumab Post Induction Chemotherapy + SBRT for First Line Treatment Stage IV Pancreatic Cancer

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

Blood and tumor samples will be analyzed for various biomarkers. Initial biomarkers to be tested include proteins such as PDL-1, functional DNA repair assays, stromal elements, immune cells ratio, DNA and RNA next generation sequencing

Proportion of subjects showing best overall response of complete response (CR) or partial response (PR)

Proportion of subjects with best overall response of CR or PR, in progressors who continue to receive low dose radiation and re-challenge nivolumab and ipilimumab

Duration of time from first dose of SBRT until confirmed objective disease progression or death (or date of last documentation of being alive).

Duration of time until 2nd confirmed objective disease progression or death (or last documentation of being alive).

Duration of time from diagnosis until death (or date of last documentation of being alive). Survival data may be obtained via contact with the patient, patient's family, or through a review of the patient's notes, or through the use of public records.

Any new condition or change from baseline will be included in summary tables.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Maintenance Ipilimumab + Nivolumab Post Induction Chemotherapy + SBRT for First Line Treatment Stage IV Pancreatic Cancer	NCT05088889	Stage IV Pancre...	Nivolumab ipilimumab Stereotactic bo... Low dose irradi...	18 Years -	Sheba Medical Center
Maintenance Ipilimumab + Nivolumab Post Induction Chemotherapy + SBRT for First Line Treatment Stage IV Pancreatic Cancer	NCT05088889	Stage IV Pancre...	Nivolumab ipilimumab Stereotactic bo... Low dose irradi...	18 Years -	Sheba Medical Center

Spots Global Cancer Trial Database for low dose irradiation