Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Breast Neoplasms

Pancreatic Neoplasms

Carcinoma, Non-Small-Cell Lung

Head and Neck Neoplasms

Sarcoma

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Carcinoma

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Cisplatin

Palbociclib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive cisplatin IV over 30-60 minutes on day 1 and palbociclib PO QD on days 2-22. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients receive carboplatin IV over 30-60 minutes on day 1 and palbociclib PO QD on days 2-22. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Olatunji B Alese, MD

This phase I trial studies the side effects and best dose of palbociclib with cisplatin or carboplatin in treating patients with solid tumors that have spread to other places and usually cannot be cured or controlled with treatment. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving palbociclib with cisplatin or carboplatin may help stop tumor growth in patients with advanced solid tumors.

PRIMARY OBJECTIVES:

I. Assess the safety and tolerability of palbociclib when administered along with cisplatin or carboplatin.

II. Establish the recommended phase 2 dose (RP2D) of the tested combinations.

SECONDARY OBJECTIVES:

I. Characterize the pharmacokinetic (PK) profiles of cisplatin, carboplatin.

II. Obtain preliminary evidence of anti-tumor efficacy of the tested combination regimens.

III. Conduct PK/pharmacodynamics (PD) correlative analyses using palbociclib trough concentration and cyclin-dependent kinase 4 (CDK4) inhibition read-outs in tumor and surrogate samples collected on course 1 day 22 (C1D22).

IV. Assess potential association between tissue-based biomarkers and efficacy.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 arms.

ARM A: Patients receive cisplatin intravenously (IV) over 30-60 minutes on day 1 and palbociclib orally (PO) once daily (QD) on days 2-22. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive carboplatin IV over 30-60 minutes on day 1 and palbociclib PO QD on days 2-22. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for up to 4 weeks.

Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors

A Phase 1 Study of Palbociclib in Combination With Cisplatin or Carboplatin in Advanced Solid Malignancies

Will be summarized and presented along with 95% exact confidence intervals.

Within-subject and between-cohort comparisons of Cmax will be performed using Wilcoxon (non-parametric) test.

Pfizer

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Emory University

Principal Investigator

Symptoms and General Pathology

Musculoskeletal Diseases

Osteosarcoma

Neoplasm Metastasis

Bone Neoplasms

Neoplasms, Unknown Primary

Neoplastic Processes

Bone Diseases

Paclitaxel

Albumin-Bound Paclitaxel

Tislelizumab

Immunomodulating Agents

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Patients with bone metastases from cancer of unknown primary (BMCUP) diagnosed according to the criteria defined in the 2015 European Society of Medical Oncology (ESMO) clinical Practice Guidelines and with bone metastases confirmed by imaging and histology that cannot be completely resected

1. Cisplatin: 100mg/m2, injected intravenously every 3 weeks, 8 cycles (period 21 days)
2. Paclitaxel (albumin-bound) : paclitaxel, 175mg/m2, given intravenously every 3 weeks for 8 cycles (period 21 days).
3. Tislelizumab: 200mg, given intravenously every 3 weeks until disease progression or unacceptable toxicity or death or subject withdrawal of informed consent.

1. Cisplatin: 100mg/m2, injected intravenously every 3 weeks, 8 cycles (period 21 days)
2. Paclitaxel (albumin-bound) : paclitaxel, 175mg/m2, given intravenously every 3 weeks for 8 cycles (period 21 days).
3. Tislelizumab: 200mg, given intravenously every 3 weeks until disease progression or unacceptable toxicity or death or subject withdrawal of informed consent.

Tislelizumab plus chemotherapy

Wei Xu, Doctor

Bo Li, Doctor

Jianru Xiao, Profession

Wei Xu, Profession

Bo Li, Profession

Hao Jiang, Doctor

Pengru Wang, Doctor

Through scientific and rigorous design, implementation, follow-up and statistics, the sponsor aims to explore the clinical efficacy and safety of Tislelizumab combined with chemotherapy (platinum + paclitaxel) in the treatment of patients with bone metastases cancer with unknown primary, and provide a better treatment plan for these patients.

1. Primary outcome: Objective response rate (ORR)
2. Secondary outcomes: disease control rate (DCR), duration of remission (DOR), progression-free disease (PFS), overall survival (OS), median PFS, median OS, stratification based on clinical features and PD-L1 expression, adverse reactions (AEs), and quality of life.

Unknown primary metastatic carcinoma is a general term for independent metastatic tumors, which are histologically confirmed as metastatic carcinoma but whose primary anatomic site cannot be determined after examination. It accounts for about 3% \~ 5% of all new cancers in humans, and is the 7th \~ 8th most common malignant tumor and the 4th most common fatal cancer in humans.CUP is typically characterized by aggressive and early metastasis and unpredictable metastasis. The disease is not a single disease, but a heterogeneous collection of tumors composed of different primary tumor types that cannot be recognized Bone is the third most common site of CUP, and bone metastases from cancer of unknown primary (BMCUP) is a type of CUP with poor overall prognosis. The primary site of the tumor was determined. BMCUP is a type of heterogeneous tumor with bone metastases confirmed by biopsy but whose primary anatomic site cannot be determined after detailed history, physical examination and relevant experimental examination.BMCUP accounts for about 10% of CUP, which is common in adults with a median onset age of 65-90 years and slightly more in men than women.The spine is the most common site of BMCUP, followed by the pelvis and long bones.Adenocarcinoma was the main pathologic type of BMCUP, with low and medium differentiated adenocarcinoma (64%), undifferentiated carcinoma (20%), neuroendocrine carcinoma (9%) and squamous cell carcinoma (7%).Patients with BMCUP usually have a poor prognosis, with an average survival of 3 to 12 months.

Currently, empire-based chemotherapy, including platinum and taxanes, is still the main treatment for CUP and BMCUP, but the effect is not ideal and the survival rate is very low (median overall survival, about 6-9 months).In recent years, gene expression profiling is a new diagnostic technique, which makes it possible to predict the origin of tumor tissue based on the expression profiling of specific sites. Several of these molecular profiling methods, including reverse transcription polymerase chain reaction (RT-PCR) analysis and DNA microarray analysis, have been developed to trace the primary foci of CUP and BMCUP. In addition, the results of gene expression profiling can indicate the information of tumor genetic abnormalities and thus potential targeted drugs. However, Hayashietal etal., published in JCO in 2019, concluded that "although the prediction of the primary site seems to have prognostic value,However, cuP-site-specific therapy based on microarray mapping did not result in a significant improvement in 1-year survival compared with empirical platinum-paclitaxel therapy ". At present, the systemic treatment of CUP and BMCUP is still not ideal, and finding new effective and safe drug treatment is the key research content of this kind of disease.

In recent years, with the deepening of the research on the regulation mechanism of the immune system and the emergence of immune checkpoint inhibitors, biological therapy with tumor immunotherapy as the core has developed rapidly, and now has become another major cancer treatment mode after chemotherapy and targeted drugs. When the body encounters cancer cells, antigen presenting cells (APC) capture antigen (Ag) and present it to T cells. After activation of T cells, programmed cell death protein 1 (PD-1) receptor can be expressed in T cells and transmit negative regulatory signals to T cells by binding to PD-L1 ligand on tumor cells and APC surface, thus inhibiting the immune response. Immune checkpoint inhibitors block the binding of the PD-1 receptor to the PD-L1 ligand, thereby enhancing the anti-tumor immune response.Pd-1 and PD-L1 inhibitors play a significant antitumor effect in lung cancer, melanoma, kidney cancer and other malignant tumors, but there are no literature reports on the efficacy and safety of immune checkpoint inhibitors in CUP and BMCUP. According to the search results of our treatment group, ClinicaTtrails. Gov has registered clinical trials under research, and the studies related to the application of immune checkpoint inhibitors in CUP include Tom Baker Cancer Center in Canada, a prospective single-arm study of paprizumab monotherapy in CUP patients with poor prognosis, which is still recruiting patients.

Tislelizumab is a humanized IgG4 monoclonal antibody against PD-1, which is an "immune checkpoint" inhibitor. It can bind to the PD-1 receptor on the cell surface and block the binding of PD-L1 and PD-L2. Thus, the escape state of tumor immunity is reversed and the killing activity of T cells is restored. Compared with other PD-1 antibodies, Tislelizumab can reduce the binding of FcγR on macrophages, thereby reducing antibody-dependent phagocytosis and possibly improving the resistance of PD-1 antibodies. It was approved for market in China on December 26, 2019. For the treatment of patients with recurrent or refractory classic Hodgkin's lymphoma, urothelial carcinoma, non-small cell lung cancer, hepatocellular carcinoma. In terms of safety, the most common grade 3 or higher adverse reactions associated with Tislelizumab were elevated glutamyltransferase, anemia, and glutamic-oxalacetic transaminase.

This is a prospective, single-arm, open phase II clinical study

Prior to enrollment in the study, doctors asked and recorded the patient's medical history, and if eligible participants volunteered to participate in the study, they would sign informed consent.If they are not willing to participate in the study, we will do the usual treatment

Tislelizumab Combined With Chemotherapy in the Treatment of Bone Metastases of Unknown Primary

Tislelizumab Combined With Chemotherapy in the Treatment of Bone Metastases of Unknown Primary: A Prospective, Open-label, Single-arm Clinical Study

Proportion of patients whose tumor volume shrinks to a predetermined value and maintains the minimum time limit

Proportion of patients whose tumors shrank or remained stable for a certain amount of time

The time between the first tumor evaluation for CR or PR and the first evaluation for PD (Progressive Disease) or death from any cause

The time span from the start of treatment to the onset of secondary growth

The time between randomization and the death of the patient from any cause

Fifty percent of patients survival with respect to the The time span from the start of treatment to the onset of secondary growth

Fifty percent of patients survival with respect to The time between randomization and the death of the patient from any cause

The occurrence of adverse events was recorded

Wei Xu

Professor of Orthopaedic department of Changzheng Hospital

Bevacizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunologic Factors

Recombinant humanized anti-PD-1 monoclonal antibody injection:200mg once every 3 weeks

Recombinant humanized anti-PD-1 monoclonal antibody injection

Xichun Hu, MD, PhD

Xichun Hu

This trial is a single-center, prospective, single-arm Phase II clinical study. The purpose is to evaluate the efficacy and safety of recombinant humanized anti-PD-1 monoclonal antibody combined with albumin paclitaxel and bevacizumab in the second-line treatment of patients with unknown primary tumors.

Recombinant humanized anti-PD-1 monoclonal antibody combined with albumin paclitaxel and bevacizumab treatment, once every 3 weeks, treatment until disease progression, intolerable adverse reactions, patient death or withdrawal informed agree.After treatment, the patients was followed up every 9 weeks for follow-up treatment and survival.

PD-1 Inhibitor and Nab-paclitaxel and Bevacizumab in CUP

Phase 2, Open-label, Single Center, Prospective Study of Recombinant Humanized Anti-PD-1 Monoclonal Antibody Combined With Nab-paclitaxel and Bevacizumab in the Second-line Treatment of Patients With Cancer of Unknown Primary (CUP)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors	NCT02897375	Solid Neoplasm Stage III Pancr... Stage IIIA Brea... Stage IIIA Non-... Stage IIIB Brea... Stage IIIB Non-... Stage IIIC Brea... Stage IV Breast... Stage IV Non-Sm... Stage IVA Pancr... Stage IVB Pancr... Sarcoma Colorectal Canc... Head and Neck C... Cancer of Unkno... Bladder Cancer Ovarian Cancer	Carboplatin Cisplatin Palbociclib	18 Years -	Emory University
Tislelizumab Combined With Chemotherapy in the Treatment of Bone Metastases of Unknown Primary	NCT05241132	Cancer of Unkno... Bone Cancer Met... Tislelizumab Gene Mutation-R... Immune Evasion,... Chemotherapy Ef...	Tislelizumab pl...	18 Years -	Shanghai Changzheng Hospital
PD-1 Inhibitor and Nab-paclitaxel and Bevacizumab in CUP	NCT04848597	Cancer of Unkno...	Recombinant hum...	18 Years - 75 Years	Fudan University
Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors	NCT02897375	Solid Neoplasm Stage III Pancr... Stage IIIA Brea... Stage IIIA Non-... Stage IIIB Brea... Stage IIIB Non-... Stage IIIC Brea... Stage IV Breast... Stage IV Non-Sm... Stage IVA Pancr... Stage IVB Pancr... Sarcoma Colorectal Canc... Head and Neck C... Cancer of Unkno... Bladder Cancer Ovarian Cancer	Carboplatin Cisplatin Palbociclib	18 Years -	Emory University
Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors	NCT02897375	Solid Neoplasm Stage III Pancr... Stage IIIA Brea... Stage IIIA Non-... Stage IIIB Brea... Stage IIIB Non-... Stage IIIC Brea... Stage IV Breast... Stage IV Non-Sm... Stage IVA Pancr... Stage IVB Pancr... Sarcoma Colorectal Canc... Head and Neck C... Cancer of Unkno... Bladder Cancer Ovarian Cancer	Carboplatin Cisplatin Palbociclib	18 Years -	Emory University

Spots Global Cancer Trial Database for cancer of unknown primary