Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Pembrolizumab

Trametinib

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients with locally recurrent pancreatic cancer were randomly allocated to SBRT plus Pembrolizumab and Trametinib or SBRT plus Gemcitabine.

Cyberknife plus Pembrolizumab and Trametinib

Cyberknife plus Gemcitabine

Huo Jun Zhang, MD., PH.D

Hypothesis: Survival benefits could be found in SBRT Plus Pembrolizumab and Trametinib compared with SBRT plus gemcitabine.

Background and aim:

Pancreatic cancer is one of the most lethal malignancies and fourth leading cause of cancer death in both genders in US, where the mortality and incidence increase over the past decade with a lowest 5-year survival rate of 9% among all cancers. Although surgical resection is deemed to provide long-term disease control, only 20% patients were candidates for upfront surgery and unfortunately, even when adjuvant chemotherapy is prescribed, about 50% of patients will suffer local recurrence. Despite of emergence of immunotherapy as a new treatment paradigm, little improvement of outcomes has been found in pancreatic cancer. This may be ascribed to its inherent genetic mutations and immunosuppressive microenvironment. It has been demonstrated that radiotherapy could enhance the release and uptake of tumor-associated antigens, thus promoting antitumor T cell priming, and enhancing access to tumors due to effects both on the tumor vasculature and the chemokine milieu.

Despite of emergence of immune checkpoint inhibitors as a novel treatment paradigm for cancers, the results of investigations about the efficacy of immunotherapy alone for pancreatic cancer was disappointing. Due to enhanced immunogenicity of tumor irradiation, the underlying rationale of combination of radiotherapy and immunotherapy is that radiation can noninvasively prime the immune system against tumor cells, where antigen presentation and co-stimulation are facilitated, thus creating immune responses against previously hidden epitopes that are shared among distant metastases, while immune checkpoint inhibitors can reverse the immunosuppressive effects of the tumor microenvironment, thus facilitating antitumor immunity.

Although oncogenic mutations in KRAS are frequent in pancreatic cancer, KRAS proteins are difficult to be targeted due to high affinity for GTP and/or GDP. Therefore, efforts have been made to develop therapies targeting the major downstream effector pathways, which include the RAS-RAF-MEK-ERK and PI3K-PDPK1-AKT signaling pathways. MEK inhibitor trametinib alone or in combinations with chemotherapy or autophagy inhibitor hydroxychloroquine may probably have positive effects on tumor regression.

Regarding local recurrence after surgery, it was recommended that chemotherapy with optional radiotherapy may be the first-line treatment without addition of targeted therapy or immunotherapy owing to that no studies have investigated the efficacy of this regimen. Therefore, the aim of our study was to compare the outcomes between stereotactic body radiation therapy (SBRT) with pembrolizumab and trametinib and SBRT with gemcitabine for locally recurrent pancreatic cancer after surgical resection.

Study procedure:

1. All surgical specimens underwent immunohistochemical staining of PD-L1, classified as TC3 ≥ 50% or TC2 ≥ 5% but \< 50% or TC1 ≥ 1% but \<5% and IC3 ≥ 10% or IC2 ≥ 5% but \< 10% or IC1 ≥ 1% but \<5%.
2. KRAS mutations were analyzed by PCR amplification and direct sequencing of exon 2. Restriction Length Fragment Polymorphism method was used for further confirmation.
3. In the SBRT plus pembrolizumab and trametinib group, 200mg pembrolizumab was administered intravenously every 3 weeks and 2mg trametinib was given orally once daily.
4. In the SBRT plus gemcitabine group, patients received intravenous gemcitabine (1000mg/m2) on day 1 and 8 of each 21-day cycle for eight cycles in the absence of disease progression.
5. The prescribed dose of SBRT varies from 35-40Gy/5f with a single dose of 7-8Gy.

SBRT Plus Pembrolizumab and Trametinib for Pancreatic Cancer

Stereotactic Body Radiation Therapy Plus Pembrolizumab and Trametinib vs. Stereotactic Body Radiation Therapy Plus Gemcitabine for Locally Recurrent Pancreatic Cancer After Surgical Resection: an Open-label, Randomized, Controlled, Phase 2 Trial

The time from the start of treatment to death

The number of patients alive at 1 year and 2 years.

Treatment-related adverse effects are determined by National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.

The time from the start of treatment until documentation of any clinical or radiological disease progression or death, whichever occurred first. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

The proportion of patients without disease progressions at 1 year and 2 years.

The analysis of quality of life is based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30). All scales and subscales range from 0 to 100. Regarding physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning and global health, higher scores may indicate better outcomes. In the case of fatigue, nausea and vomitting, pain, dyspnea, insomina, appetite loss, constipation, diarrhea and financial difficulties, lower scores may indicate better outcomes. Scales of all items are independent and not combined to compute a total score.

Changhai Hospital

Director of Radiation Oncology Department

Patients with locally recurrent pancreatic cancer were randomly allocated to SBRT plus Pembrolizumab and Trametinib or SBRT plus Gemcitabine.

Cyberknife plus Gemcitabine: Radiation therapy plus drug

SBRT Plus Gemcitabine

Patients with locally recurrent pancreatic cancer were randomly allocated to SBRT plus Pembrolizumab and Trametinib or SBRT plus Gemcitabine.

Cyberknife plus Pembrolizumab and Trametinib: Radiation therapy plus drug

SBRT Plus Pembrolizumab and Trametinib

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

China

Region of Enrollment

IC1 or TC1

IC2 or TC2

IC3 or TC3

PD-L1 tumor cell (TC) expression was scored as the percentage of PD-L1 TC, which was stratified as TC3 ≥ 50% or TC2 ≥ 5% but \< 50% or TC1 ≥ 1% but \<5%. PD-L1 tumor-infiltrating immune cells (IC) expression was scored as the percentage of tumor area stained positive, which was classified as IC3 ≥ 10% or IC2 ≥ 5% but \< 10% or IC1 ≥ 1% but \<5%. Briefly, the higher expression of TCor IC indicated worse outcomes.

PD-L1 intensity

The major limitation of the study was the small number of the randomized patients.

Huojun Zhang

The Median Survival Time Will be Determined.

1-year OS rate

2-year OS rate

One- and Two-year Overall Survival Rate Will be Determined.

Grade 3 pyrexia

Grade 3 vomitting

Grade 3 and 4 increased ALT or AST

Grade 3 stomatitis

Grade 3 rash

Grade 3 and 4 neutropenia

Grade 3 thrombocytopenia

Grade 3 increased blood bilirubin

Grade 3 hypokalemia

Grade 3 hyponatremia

Grade 3 pneumonia

Grade 3 hypertension

Treatment-related Adverse Effects Will be Determined.

The Median Progression Free Survival Time Will be Determined.

1-year PFS rate

2-year PFS rate

One- and Two-year Progression Survival Rate Will be Determined. Will be Determined.

Physical functioning

Role functioning

Emotional functioning

Cognitive functioning

Social functioning

Global health

Fatigue

Nausea and vomitting

Pain

Dyspnea

Insomina

Appetite loss

Constipation

Diarrhea

Financial difficulties

The Quality of Life Will be Analyzed.

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Hyman Muss, MD

The primary purpose of this study is to measure the association between baseline expression of the senescence effector protein p16INK4a and myelosuppression due to chemotherapy in patients with breast cancer. Patients with Stage I-IV breast cancer will be included and myelosuppression will be assessed after the first cycle of chemotherapy via measurement of an absolute neutrophil count (ANC) measured one time between days 7-11 post cycle one. Study subjects will also be asked to complete a brief health behaviors questionnaire to gather information on other relevant variables.

Study of the P16 Gene as a Predictor of Myelosuppression in Breast Cancer Patients

LCCC 1027: Expression Of P16INK4a As A Predictor Of Myelosuppression In Patients With Breast Cancer

To measure and correlate baseline p16INK4a expression in subjects with stage I-IV breast cancer starting a new course of chemotherapy with a post cycle 1 chemotherapy absolute neutrophil count (ANC).

To explore the associations between p16INK4a expression at baseline and amount of vigorous physical activity, smoking habits, and weekly alcohol consumption.

To explore the associations between p16INK4a expression at baseline and other chemotherapy-related toxicities, including the maximum toxicity experienced during that course of chemotherapy.

To explore the associations between p16INK4a expression at baseline and type of chemotherapy received, co-morbidities, concomitant medications, and tumor characteristics.

UNC Lineberger Comprehensive Cancer Center

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Patients with low grade disease (grade 1 or 2) with positive or negative mutational status

per os, 60mg/j, until progression or unacceptable toxicity

BKM120

Isabelle Ray-Coquard, MD

This study is to determine the clinical efficacy of BKM120 as monotherapy in the treatment of initial or recurrent metastatic endometrial cancer after first line radio chemotherapy.

Clinical efficacy will be determined by the non-progression rate at 3 or 2 months depending on the group of patients. The primary endpoint is the non-progression rate at 3 months (12 weeks) for the patient group whose disease is painless (low grade tumor = stratum 1) and the non-progression rate at 2 months (8 weeks) for the group of patients with an aggressive disease (high grade tumor = stratum 2).

Disease progression is defined by the RECIST 1.1 criteria

GINECO-EN102b - BKM120 as Monotherapy in the Treatment of Initial or Recurrent Metastatic Endometrial Cancer

Phase 2 Multicenter Study to Assess the Safety and Efficacy of BKM120 as Monotherapy in Treatment of Initial or Recurrent Metastatic Endometrial Cancer After 1st Line Therapy in Patients Who Cannot Undergo Local Surgery and/or Radiotherapy

To determine the clinical efficacy of BKM120 as monotherapy in the treatment of initial or recurrent metastatic endometrial cancer after first line radio chemotherapy.

To assess patient safety and the tolerance of BKM120 administered as monotherapy at the daily dose of 100 mg.

To evaluate the objective response rate according to RECIST 1.1

To evaluate the duration of the response. For patients in complete remission, the duration of the response will be calculated from the day on which a complete response is determined for the first time up to progression.

For patients in partial remission, the duration of the response will be the overall response period calculated from the administration of the first treatment cycle up to the date of progression.

ARCAGY/ GINECO GROUP

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, Follicular

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Obinutuzumab

Prednisone

Bendamustine Hydrochloride

Rituximab

Vincristine

Immunomodulating Agents

Immunoglobulins

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Patients will start immunochemotherapy with one of the approved regimens (R-CHOP, R-Bendamustine, G-CHOP, G-Bendamustine, G-CVP).

Patients randomized to Arm A will receive an induction immunochemotherapy at full doses (standard schedule).

After cycle 4, patients will be assessed for response and will complete their planned therapy if at least a stable disease is confirmed.

At the end of induction responding patients (CR, PR) will be addressed to a standard anti-CD20 maintenance (1 dose every 8 weeks for two years) with the same Monoclonal Antibody (MoAb) given during induction.

Patients will start immunochemotherapy with one of the approved regimens (R-CHOP, R-Bendamustine, G-CHOP, G-Bendamustine, G-CVP).

Patients randomized to Arm B will start their induction treatment with 4 cycles of the immunochemotherapy standard dose chosen by the physician: after cycle 4, patients will be assessed for response and will proceed with subsequent treatment based on the quality of their response. Specifically:

* Patients achieving a CR will receive a shortened treatment: in detail, they won't receive any further chemotherapy but will complete induction with 4 additional cycles of only the Monoclonal Antibody (MoAb) given during the first four cycles;
* In case if response less than CR, (PR,SD), patients will complete treatment as planned for patients in Arm A.

At the end of induction responding patients (CR, PR) will be addressed to a standard anti-CD20 maintenance (1 dose every 8 weeks for two years) with the same Monoclonal Antibody (MoAb) given during induction.

Arm A (Standard arm):

4 cycles of Rituximab-bendamustine Q28 (28-days cycles); Patients will undergo an early restaging after cycle 4: those with at least a stable disease will complete the induction treatment with 2 cycles of R-bendamustine Q28 + 2 cycles Q28 of rituximab;

Both Arms:

Whichever the regimen, in responding patients (Complete Remission CR, Partial Remission PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction.

Patients in both arms with progressive disease at any time and patients in stable disease (SD) at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

Immunochemotherapy regimen: Rituximab-bendamustine (Arm A)

Arm B (Experimental arm):

4 cycles of Rituximab-bendamustine Q28 (28-days cycles);

After cycle 4 patients will undergo an early restaging. Induction therapy shall be completed based on the response achieved and on the treatment chosen as below specified:

* if in CR: patients will receive no more chemotherapy but will complete induction with the MoAb only, in this case: 4 cycles of rituximab;
* if less than CR (PR, SD): the immunochemotherapy program will be completed as outlined for Arm A: 2 cycles of R-bendamustine Q28 + 2 cycles Q28 of rituximab;

Both Arms:

Whichever the regimen, in responding patients (CR, PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction.

Patients in both arms with progressive disease at any time and patients in SD at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

Immunochemotherapy regimen: Rituximab-bendamustine (Arm B)

Arm A (Standard arm):

4 cycles of R-CHOP Q21 (21-days cycles); R-CHOP = Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

Patients will undergo an early restaging after cycle 4: those with at least a stable disease will complete the induction treatment with 2 cycles of R-CHOP Q21 + 2 cycles Q21 of rituximab;

Both Arms:

Whichever the regimen, in responding patients (Complete Remission CR, Partial Remission PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction.

Patients in both arms with progressive disease at any time and patients in stable disease (SD) at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion: these patients will be included in the analysis planned by the study.

Immunochemotherapy regimen: R-CHOP (Arm A)

Arm B (Experimental arm):

4 cycles of R-CHOP Q21 (21-days cycles); R-CHOP = Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

After cycle 4 patients will undergo an early restaging: induction therapy shall be completed based on the response achieved and on the treatment chosen:

* if in CR: patients will receive no more chemotherapy but will complete induction with the MoAb only, in this case: 4 cycles of rituximab;
* if less than CR (PR, SD): the immunochemotherapy program will be completed as outlined for Arm A: 2 cycles of R-CHOP Q21+ 2 cycles Q21of rituximab

Both Arms: in responding patients (CR, PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 MoAb used for induction.

Patients in both arms with progressive disease at any time and patients in SD at the EOI shall be considered for salvage therapy at clinician discretion: these patients will be included in the analysis.

Immunochemotherapy regimen: R-CHOP (Arm B)

Arm A (Standard arm):

4 cycles of G-bendamustine Q28 (28-days cycles); G-Bendamustine = Obinutuzumab and Bendamustine

Patients will undergo an early restaging after cycle 4: those with at least a stable disease will complete the induction treatment with 2 cycles of G-bendamustine Q28 (28-days cycles);

Both Arms:

Whichever the regimen, in responding patients (Complete Remission CR, Partial Remission) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction.

Patients in both arms with progressive disease at any time and patients in Stable Disease SD at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

Immunochemotherapy regimen: G-bendamustine (Arm A)

Arm B (Experimental arm):

4 cycles of G-bendamustine Q28 (28-days cycles); G-Bendamustine = Obinutuzumab and Bendamustine

After cycle 4 patients will undergo an early restaging. Induction therapy shall be completed based on the response achieved and on the treatment chosen as below specified:

* if in CR: patients will receive no more chemotherapy but will complete induction with the Monoclonal Antibody (MoAb) only, in this case 2 cycles of obinutuzumab;
* if less than CR (PR, SD): the immunochemotherapy program will be completed as outlined for Arm A: 2 cycles of G-bendamustine Q28;

Both Arms: in responding patients (CR, PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 (MoAb) used for induction.

Patients in both arms with progressive disease at any time and patients in SD at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

Immunochemotherapy regimen: G-bendamustine (Arm B)

Arm A (Standard arm):

4 cycles of G-CHOP Q21 (21-days cycles) G-CHOP = Obinutuzumab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

Patients will undergo an early restaging after cycle 4: those with at least a stable disease will complete the induction treatment with 2 cycles of G-CHOP Q21 + 2 cycles Q21 of obinutuzumab;

Both Arms:

Whichever the regimen, in responding patients (Complete Remission CR, Partial Remission PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction.

Patients in both arms with progressive disease at any time and patients in stable disease (SD) at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

Immunochemotherapy regimen: G-CHOP (Arm A)

4 cycles of G-CHOP Q21 (21-days cycles) G-CHOP = Obinutuzumab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

After cycle 4 patients will undergo an early restaging. Induction therapy shall be completed based on the response achieved and on the treatment chosen as below specified:

* if in CR: patients will receive no more chemotherapy but will complete induction with the Monoclonal Antibody (MoAb) only, in this case: 4 cycles of obinutuzumab;
* if less than CR (PR, SD): the immunochemotherapy program will be completed as outlined for Arm A: 2 cycles of G-CHOP Q21 + 2 cycles Q21 of obinutuzumab;

Both Arms: in responding patients (CR, PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 MoAb used for induction.

Patients in both arms with progressive disease at any time and patients in SD at the EOI shall be considered for salvage therapy at clinician discretion.

Immunochemotherapy regimen: G-CHOP (Arm B)

Arm A (Standard arm):

4 cycles of G-CVP Q21 (21-days cycles) G-CVP = Obinutuzumab, Cyclophosphamide, Vincristine, Prednisone.

Patients will undergo an early restaging after cycle 4: those with at least a stable disease will complete the induction treatment with 4 cycles of G-CVP Q21;

Both Arms:

Whichever the regimen, in responding patients (Complete Remission CR, Partial Remission PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 Monoclonal Antibody (MoAb) used for induction.

Patients in both arms with progressive disease at any time and patients in stable disease SD at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

Immunochemotherapy regimen: G-CVP (Arm A)

Arm B (Experimental arm):

4 cycles of G-CVP Q21 (21-days cycles) G-CVP = Obinutuzumab, Cyclophosphamide, Vincristine, Prednisone.

After cycle 4 patients will undergo an early restaging. Induction therapy shall be completed based on the response achieved and on the treatment chosen as below specified:

* if in CR: patients will receive no more chemotherapy but will complete induction with the Monoclonal Antibody (MoAb) only, in this case: 4 cycles of obinutuzumab;
* if less than CR (PR, SD): the immunochemotherapy program will be completed as outlined for Arm A: 4 cycles of G-CVP Q21

Both Arms: in responding patients (CR, PR) at the end of induction a standard maintenance will follows (1 dose every 8 weeks for 2 years) with the same anti-CD20 MoAb used for induction.

Patients in both arms with progressive disease at any time and patients in SD at the End Of Induction (EOI) shall be considered for salvage therapy at clinician discretion.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SBRT Plus Pembrolizumab and Trametinib for Pancreatic Cancer	NCT02704156	Pancreatic Canc...	Cyberknife plus... Cyberknife plus...	18 Years -	Changhai Hospital
Study of the P16 Gene as a Predictor of Myelosuppression in Breast Cancer Patients	NCT01305954	Breast Cancer		18 Years -	UNC Lineberger Comprehensive Cancer Center
GINECO-EN102b - BKM120 as Monotherapy in the Treatment of Initial or Recurrent Metastatic Endometrial Cancer	NCT01397877	Endometrial Can...	BKM120	18 Years -	ARCAGY/ GINECO GROUP
Shortened vs Standard Chemotherapy Combined With Immunotherapy for the Initial Treatment of Patients With High Tumor Burden Follicular Lymphoma	NCT05058404	Follicular Lymp...	Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother...	18 Years -	Fondazione Italiana Linfomi - ETS
Shortened vs Standard Chemotherapy Combined With Immunotherapy for the Initial Treatment of Patients With High Tumor Burden Follicular Lymphoma	NCT05058404	Follicular Lymp...	Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother... Immunochemother...	18 Years -	Fondazione Italiana Linfomi - ETS

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