Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Hematinics

Vitamins

Gemcitabine

Vitamin A

Retinol palmitate

Dexamethasone

Pemetrexed

Cisplatin

Dexamethasone acetate

Folic Acid

Vitamin B Complex

Vitamin B 12

Hydroxocobalamin

Trace Elements

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antimetabolites

Retinol

Folinic Acid

Methylcobalamin

Folate

Vitamin B9

Vitamin B12

Cobalamin

Cyanocobalamin

Patients received cisplatin 75mg/m2 plus pemetrexed 500 mg/m2 on day 1.Chemotherapy was repeated every 3 weeks for a maximum of six cycles.Patients received dexamethasone prophylaxis of 3.75mg orally twice per day on the day before, the day of, and the day after each day-1 treatment. patients received oral folic acid (1,000ug)daily and a vitamin B12 injection (1,000 ug) every 9 weeks, beginning 1 to 2 weeks before the first dose and continuing until 3 weeks after the last dose of study treatment

cisplatin, dexamethasone,vitamin B12, folic acid

cisplatin 75mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8

cisplatin, gemcitabine

Li Zhang, MD

A phase III trial has demonstrated that in advanced non-small cell lung cancer (NSCLC) cisplatin/ pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. Moreover,this trial showed survival differences based on histologic type. The investigators want to research some biomarkers that can predict clinical outcomes.

Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin for Advanced NSCLC Metastatic Non-small Cell Lung Cancer

A Phase 2,Open-label Study of First Line Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin for Advanced and Metastatic Non Small Cell Lung Cancer and Biomarker Study

Sun Yat-sen University

Professor

cisplatin, dexamethasone,vitamin B12, folic acid: Patients received cisplatin 75mg/m2 plus pemetrexed 500 mg/m2 on day 1.Chemotherapy was repeated every 3 weeks for a maximum of six cycles.Patients received dexamethasone prophylaxis of 3.75mg orally twice per day on the day before, the day of, and the day after each day-1 treatment. patients received oral folic acid (1,000ug)daily and a vitamin B12 injection (1,000 ug) every 9 weeks, beginning 1 to 2 weeks before the first dose and continuing until 3 weeks after the last dose of study treatment

Group A

cisplatin, gemcitabine: cisplatin 75mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8

Group B

Total

Age, Categorical

Sex: Female, Male

China

Region of Enrollment

Dr. Li Zhang

Progression Free Survival (PFS)

Response Rate

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Patients will be followed with computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

Receive two cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1 and gemcitabine 1000mg/m2 D1 and D8 at every 21 days. After that, patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

Two additional cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1 and gemcitabine 1000mg/m2 D1 and D8 at every 21 days.

Follow-up

Michelle S Almeida, PhD

Rachel H Machado, MCS

This study hypothesizes that patients who persist with cell-free human papillomavirus deoxyribonucleic acid (cfHPV-DNA) plasma expression at the end of standard treatment, can derive the benefit of using adjuvant chemotherapy in locally advanced cervical cancer (CC). After standard treatment based on concomitant chemoradiotherapy regime, a qualitative and quantitative research of cfHPV-DNA in plasma of patients will be conducted. Those with a negative qualitative research result will leave the study. Patients who have positive research for plasma 16/18 cfHPV-DNA at the end of chemoradiotherapy treatment will be randomized to receive two additional cycles of adjuvant chemotherapy or observation. Patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

A prospective, randomized, multicenter, national, superiority, parallel, clinical trial, design to evaluate implementation components for conducting a national clinical trial using adjuvant chemotherapy in patients with locally advanced cervical cancer, selected by cfDNA-HPV biomarker. At the end of this pilot study, reaching feasibility goal, it is proposed to amplify size sample, with the same design.

Patients will be randomized by stratified randomization process to belong to one of the groups: control (Group B) or intervention (Group C), emphasizing homogeneity of risk factors between them. A randomized list will be generated by using a suitable software, using variable size blocks (2 or 4), with stratification for site and staging. The confidentiality of the randomization list will be maintained through an automated, centralized, Internet-based randomization system, available 24 hours a day (RedCap). Selected patients must receive standard treatment based on concomitant chemoradiotherapy regime, with dose of radiation of 40-50 greys (Gy) (considering additional boost of 10-15 Gy in lymph nodes, radiologically or surgically, compromised) and brachytherapy of 30-40 Gy and cisplatin 40mg/m2 weekly. After four weeks of the end of treatment, a qualitative and quantitative research of cfHPV-DNA in plasma of patients will be conducted. Those with a negative qualitative research result will leave the study. Patients who have positive research for plasma 16/18 cfHPV-DNA at the end of chemoradiotherapy treatment will be randomized to receive two additional cycles of adjuvant chemotherapy or observation. Patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

A prospective, randomized, multicenter, national, superiority, parallel, clinical trial, design to evaluate implementation components for conducting a national clinical trial using adjuvant chemotherapy in patients with locally advanced cervical cancer, selected by cfDNA-HPV biomarker. At the end of this pilot study, reaching feasibility goal, it is proposed to amplify size sample, with the same design. The participants will conduct a blood collection for research of cfDNA-HPV and will receive conventional treatment, gold standard currently, characterizing the descriptive phase of the research. In the second operational phase, it will happen the study randomization, designing an experimental study. The pilot study is scheduled to last one year and estimate the possibility to recruit between 30 and 50 patients during 2023.

Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer

Adjuvant Chemotherapy in Cell-free Human Papillomavirus Deoxyribonucleic Acid (cfHPV-DNA) Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer (CC)

Data could be shared after reasonable request of the principal investigator.

Accessing regulatory process, hiring and training of investigator sites.

Analyzing the impact of pandemic on disease diagnosis period.

Potential for recruiting 4 to 12 patients/month in each investigator site is sufficient to reach sample goal.

Validation of operation structure includes repository, data collection tools, logistics for intervention distribution (chemotherapy) to the participating sites, strategies for recruitment and stimulation of adherence to intervention and follow-ups.

Objectify 85% or more of adherence rates during intervention.

Aiming at reaching up to 20% during follow-ups and identification of critical factors for loss of follow-up and suggesting mitigation strategies.

Description of overall rates (non-comparative between treatment groups) of progression-free survival.

Description of overall rates (non-comparative between treatment groups) of overall survival.

Description of response rate via Response Evaluation Criteria In Solid Tumours (RECIST) criteria 1.1 2009.

Description of quality of life via European Organisation for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (QLC-C30) and a complementary module of the cervical cancer-specific Quality of Life module of the European Organization for Research and Treatment of Cancer (EORTC QLQ-CX24).

Description of tolerance to proposed intervention, by creating a Data and Safety Monitoring Board (DSMB).

University of Sao Paulo

Hospital do Coracao

Rare Diseases

Cholangiocarcinoma

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Pharmaceutical Solutions

Panitumumab

Antineoplastic Agents, Immunological

Experimental Arm with cisplatin 25mg/sq.m. at day 1 + 8, gemcitabine 1000mg/ sq.m.at day 1 + 8 and panitumumab 9mg/kg BW at day 1. Cycle will be repeated every 3 weeks.

Cisplatin 25mg/sq.m. at day 1 + 8 and Gemcitabine 1000 mg/sq.m. at day 1 + 8. Cycle will be repeated every 3 weeks.

Cisplatin 25mq/sq.m. at day 1+8 and Gemcitabine 1000mg/sq.m. at day 1 + 8 Panitumumab 9mg/kg BW at day 1

Cisplatin, Gemcitabine, Panitumumab

Cisplatin 25mq/sq.m. at day 1+8 and Gemcitabine 1000mg/sq.m. at day 1 + 8

Cisplatin, Gemcitabine

Arndt Vogel, PD Dr. MD

The purpose of this study is to determine the efficacy of panitumumab plus cisplatin/gemcitabine (CisGem) combination chemotherapy in KRAS wild-type biliary tract cancer patients without systemic pre-treatment, compared to the historical data and to the randomised control group without the antibody, which verifies the historically based assumption.

The rationale of the study is the assessment of the clinical activity of Panitumumab in conjunction with standard Cisplatin/Gemcitabine chemotherapy in patients with cholangiocarcinomas and gall bladder carcinomas in 1st-line therapy.

Cholangiocarcinoma (CCA) is an epithelial cancer originating from the bile ducts with features of cholangiocyte differentiation. CCA is the second most common primary hepatic malignancy, and epidemiologic studies suggest its incidence is increasing in Western countries. Hepatobiliary malignancies account for 13% of the 7.6 million annual cancer-related deaths worldwide and CCA accounts for approximately 20% of the deaths from hepatobiliary malignancies (Kubicka and Manns 2000; Kubicka 2004; Blechacz and Gores 2008; Malek et al. 2007).

The only curative option for patients with gallbladder- or bile duct cancer is surgical resection. Advanced CCA has a devastating prognosis. There are only limited numbers of studies about the systemic treatment options for biliary cancers. Gallbladder and bile duct carcinomas are moderately chemotherapy-sensitive tumors. The objective response rates in phase II studies with 5-FU or gemcitabine monochemotherapy are between 10 - 30 % (Kubicka et al. 2001b). Higher response rates between 20 - 50 % have been observed in phase II studies with combination chemotherapy, in particular with the combination of gemcitabine/cisplatin (Kubicka 2004; Malek et al. 2007).

Recently for the first time an improvement of overall survival has been demonstrated in a large randomized phase III trial with chemotherapy combination of cisplatin and gemcitabine (n=206) compared to gemcitabine mono-chemotherapy (n=204) (Valle et al. 2009). Median overall survival was 8,2 month in the monotherapy arm versus 11,7 month in the combination arm (p=0.002). As a consequence of this study the combination of Cisplatin (25mg/m² d1,8) and Gemcitabine (1000mg/m² d1,8) should be considered as the standard first line chemotherapy for patients with irresectable cholangio- or gallbladder carcinomas.

The growing understanding of the molecular pathogenesis of CCA opens new therapeutic options for molecular targeting (Blechacz and Gores 2008). In particular EGFR signaling appears to be important for tumor growth of CCA. Inhibition of EGFR signaling has been shown to significantly suppress CCA cell growth (Blechacz and Gores 2008). In addition EGFR can directly be activated by bile acids and promote CCA cell proliferation, a potential explanation for the tropism exerted by CCA for the biliary tree. It has been shown that EGFR activation is sustained in CCA by failure to internalize the ligand-receptor complex, a homeostatic mechanism essential for receptor inactivation. EGFR phosphorylation results in activation of the downstream kinases p42/44 MAPK and p38 MAPK, which in turn increase cyclooxygenase 2 expression in CCA cells.

Further evidence for the essential contribution of EGFR-signalling comes from studies with IL-6 (Blechacz and Gores 2008). IL-6 is a key cytokine in the pathogenesis of CCA. IL-6 is produced at high levels by CCA cells, and elevated IL-6 serum concentrations have been reported in CCA patients. It has been shown that there is a cross-communication between IL-6 and EGFR resulting in IL-6 mediated overexpression of EGFR.

Recently the first results of a randomized phase II study of gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab in patients with advanced biliary cancer have been reported (Malka et al. 2009). The primary objective of the study was a 4-month PFS rate of more than 60% in the experimental arm with cetuximab. The included patients were not monitored for RAS or B-RAF mutations. However compared to GEMOX chemotherapy (n=51), GEMOX+cetuximab (n=50) showed an increased 4-month PFS-rate (50% versus 61%) and an improved median PFS (5 versus 7 months). This is the first evidence from a randomized trial that anti-EGFR therapy may be effective for patients with cholangiocarcinomas and gallbladder carcinomas.

KRAS is a downstream molecule in the EGFR-pathway. Recently it has been shown that oncogenic RAS mutations are predictive for poor efficacy of an anti-EGFR-therapy in colorectal cancer. Conversely patients with colorectal cancers harbouring KRAS wild-type showed frequently dramatic tumor responses upon anti-EGFR-treatment, indicating that colorectal cancers with KRAS wild type are highly susceptible for an anti-EGFR-therapy. Although dysregulation of KRAS is commonly observed in malignancies, mutations of KRAS have only been described in 12% to 54% of intrahepatic CCA (Kubicka et al. 2001a; Blechacz and Gores 2008, Gruenberger et al 2009). This is in sharp contrast to pancreatic ductal carcinoma where KRAS mutations are present in approximately 90% of cancers. Thus, despite shared developmental ontology between the pancreatic ducts and the biliary tree, their adult cancers are different and may explain the negative result of a phase III studies in pancreatic cancer with Cetuximab (anti-EGFR-antibody).

Very preliminary and sparse data from a recent small phase II study with cetuximab do not allow to speculate whether the RAS status does predict the response in cholangiocarcinomas similarly to colorectal cancers (Gruenberger et al. 2009). However, due to the clear evidence of absence of efficacy in mutant KRAS colorectal cancer, the presumptive population "enrichment" should be applied in this first trial on biliary duct cancer, which is to focus on KRAS wild type patients.

Since most of the patients with CCA are treated in large centers a chemotherapy protocol with limited numbers of intravenous infusions appears to be very comfortable for patients with CCA. A further argument for the investigation of Cisplatin/Gemcitabine/Panitumumab in a randomized phase II study is the fact that the 3-week interval of the Cis/Gem protocol fits very well into the 3-week interval of the Panitumumab schedule.

PiCCA Study (Panitumumab in Combination With Cisplatin/Gemcitabine)

Panitumumab in Combination With Cisplatin/Gemcitabine Chemotherapy in Patients With Cholangiocarcinomas - a Randomized Clinical Phase II Study

The progression-free survival rate at six months (primary endpoint) is defined as the number of patients recorded to be free of progression (according to RECIST) at this time point, divided by the number of patients randomized to the respective arm.

Tumor response according to RECIST criteria within the first 48 weeks of treatment

Progression-free survival (PFS) will be defined as the time from randomisation to the time of disease progression or relapse (according to RECIST) or death, or to the date of last assessment without any such event (censored observation).

The duration of overall survival (OS) will be determined by measuring the time interval from randomisastion to the date of death or last observation (censored).

assessment/ correlation of tumor response with KRAS (mandatory)

alterations in cholangiocarcinomas and gallbladder cancer (EGFR, PTEN, BRAF)through optional translational research

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin for Advanced NSCLC Metastatic Non-small Cell Lung Cancer	NCT01194453	Non-small Cell ... Efficacy	cisplatin, dexa... cisplatin, gemc...	18 Years - 75 Years	Sun Yat-sen University
Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin for Advanced NSCLC Metastatic Non-small Cell Lung Cancer	NCT01194453	Non-small Cell ... Efficacy	cisplatin, dexa... cisplatin, gemc...	18 Years - 75 Years	Sun Yat-sen University
Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer	NCT05764044	Cervical Cancer Cervix Cancer Cervix Neoplasm	cisplatin, gemc... Follow-up	18 Years - 70 Years	Hospital do Coracao
Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer	NCT05764044	Cervical Cancer Cervix Cancer Cervix Neoplasm	cisplatin, gemc... Follow-up	18 Years - 70 Years	Hospital do Coracao
PiCCA Study (Panitumumab in Combination With Cisplatin/Gemcitabine)	NCT01320254	Cholangiocarcin...	Cisplatin, Gemc... Cisplatin, Gemc...	18 Years -	Hannover Medical School

Spots Global Cancer Trial Database for cisplatin, gemcitabine