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.

Bristol-Myers Squibb

Sheba Medical Center

Medical diractor of phase 1 clinical trials unit and Sheba pancreatic cancer program

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Recurrence

Prostatic Neoplasms

Neoplasm Metastasis

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neoplastic Processes

Hormones

Durvalumab

Radiation (SBRT) + Immunotherapy treatment (Durvalumab)

64 patients will be enrolled in this arm

Durvalumab, will be started one month prior to SBRT and then given for a total of 12 months.

Patient will receive one injection per months (1500 mg/cycle)

SBRT will be started one month after Durvalumab and patients will receive 3 fractions of radiation

Radiation (SBRT)

32 patients will be enrolled in this arm

Patients will receive only 3 fractions of radiation

Durvalumab, MEDI4736, is a immunotherapy,

SBRT (stereotactic body radiotherapy) is a procedure that uses high doses of radiation delivered to a precise target. By using special positioning and implanted markers in the body, radiologists are able to deliver a much higher dose of radiation to a cancer than traditional radiation therapy

SBRT + Durvalumab

SBRT (stereotactic body radiotherapy) is a procedure that uses high doses of radiation delivered to a precise target. By using special positioning and implanted markers in the body, radiologists are able to deliver a much higher dose of radiation to a cancer than traditional radiation therapy

SBRT

STEPHANE SUPIOT

As in other solid tumours, increasing evidence indicates that patients diagnosed with a limited number of prostate cancer metastases, so-called oligometastases, have a better prognosis compared with patients with extensive metastatic disease.

Survival of patients with three or fewer metastases was superior compared with patients with more than three lesions.

The introduction of novel imaging modalities such as Fluorocholine (FCH), Fuciclovine or Ga-PSMA PET CT has increased the detection of oligometastatic prostate cancer (PCa) recurrence, potentially justifying the use of a metastasis-directed therapy with radiotherapy (RT).

Based on several studies, SBRT is now considered as a strongly validated option in oligometastatic prostate cancer.

It is increasingly understood that cancers are recognized by the immune system, and, under some circumstances, the immune system may control or even eliminate tumors.

Programmed death-ligand 1 (PD-L1) is transmembrane protein that has been speculated to play a major role in suppressing the immune system during particular events.

PD-L1 is expressed in a broad range of cancers. Based on these findings, an anti-PD-L1 antibody could be used therapeutically to enhance antitumor immune responses in patients with cancer.

Experimental data from multiple cancer models have provided cumulative evidence of an interaction of ionizing radiation with the systemic antitumor immunity and this has created several opportunities in the field.

The oligometastatic setting appears to be the most relevant clinical situation to evaluate the immune response generated by radiotherapy and immune modifiers in patients with an intact immune system. The hypothesize is that Durvalumab will enhance immune response following SBRT targeting oligometastatic lesions. In this randomized 2:1 phase II trial of Stereotactic Body Radiation Therapy with or without durvalumab in oligometastatic hormone sensitive prostate cancer patients, Durvalumab will be started one month prior to SBRT to be able to evaluate PSA and immune response to the drug. It will be combined with SBRT and then given adjuvantly for a total of 12 months.

Prostate Cancer With OligometaSTatic Relapse: Combining Stereotactic Ablative Radiotherapy and Durvalumab (MEDI4736)

A Randomized Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) With or Without Durvalumab (MEDI4736) in Oligometastatic Recurrent Hormone Sensitive Prostate Cancer Patients

The primary outcome will be progression-free survival, defined as the time from randomization until a biochemical-clinical failure

Health-related quality of life will be evaluated using EORTC QLQ-PR25 instruments.Total score is reported

Health-related quality of life will be evaluated using self-administered EORTC QLQ-C30 questionnaire. Total score is reported

ADT will be started in both arms at time of polymetastatic disease, local progression of metastases or symptoms.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Prostate Cancer With OligometaSTatic Relapse: Combining Stereotactic Ablative Radiotherapy and Durvalumab (MEDI4736)	NCT03795207	Node; Prostate Bone Metastases Prostate Cancer...	SBRT + Durvalum... SBRT	18 Years -	Institut Cancerologie de l'Ouest
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 sbrt (stereotactic body radiation therapy)