Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Esophageal Squamous Cell Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Capecitabine

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Chemotherapy regimen (XP):

D1- D14 Capecitabine 1000 mg/m2 bid p.o. D1 Cisplatin 75 mg/m2 + NS 150mL MIV over 1hr repeat every 3 weeks

XT Regimen:

D1- D14 Capecitabine 1000 mg/m2 bid p.o. D1, D8 Genexol (Paclitaxel) 80 mg/m2 + D5W 500mL MIV over 3hrs Repeat every 3 weeks

3.2 Overview of Study Design This study is a prospective, randomized, phase II study comparing response rate between patients with XP chemotherapy versus XG chemotherapy for patients with metastatic squamous cell carcinoma.

Chemotherapy regimen (XP):

D1- D14 Capecitabine 1000 mg/m2 bid p.o. D1 Cisplatin 75 mg/m2 + NS 150mL MIV over 1hr every 3 weeks

Chemotherapy regimen (XT):

D1- D14 Capecitabine 1000 mg/m2 bid p.o. D1, D8 Genexol (Paclitaxel) 80 mg/m2 + D5W 500mL MIV over 3hrs every 3 weeks

Capecitabine plus cisplatin(XP) versus capecitabine plus paclitaxel(XT)

Young-Hyuck Im, MD, PhD

Yeon-Hee Park, MD, PhD

Until today, the 5-FU/cisplatin combination is the reference regimen with 30-45% response rates, which is most commonly used to treat patients with metastatic, recurrent or locally advanced, unresectable squamous cell carcinoma of the esophagus. Because the classical dose schedule of this two-drug combination is cisplatin 100 mg/m2 day 1 and 5-FU 1000 mg/m2/day continuous infusion for 96-120 hr, prolonged administration time and mucosal toxicity are inconvenient to the patients with the aim of palliation. Capecitabine, which is oral prodrug of 5-FU and mimic continuously-infused 5-FU, is being investigated in phase I, II and III trials for the treatment of gastric, gastroesophageal, and esophageal cancers, primarily in the first-line metastatic setting. In our experience, capecitabine plus cisplatin combination (XP) as a first-line treatment for 45 patients with advanced or recurrent esophageal squamous cell carcinoma demonstrated a promising anti-tumor activity with 57% of response rate and showed tolerable toxicity with convenience.

Paclitaxel has been also investigated as monotherapy and in combination with cisplatin in patients with advanced esophageal cancer. A Dutch phase II study demonstrated that paclitaxel combination with carboplatin had shown an encouraging confirmed response rate of 59% with 51 patients with resectable esophageal cancer in neoadjuvant setting. Another Dutch phase II study showed 43% of response rate including 4% of CR with 8 months of response duration when paclitaxel plus cisplatin administration was given for patients with metastatic esophageal cancer. Although recently first-line palliative chemotherapy regimen in esophageal cancer has been investigated, many trials have failed to show superiority to 5-FU/cisplatin combination. Since we considered that XP or XT is more effective and convenient chemotherapy regimen than 5-FU/cisplatin, this randomized phase II study was planned to compare XP with XT in terms of efficacy and tolerability.

1. Introduction and Study Rationale

   1.1 Esophageal squamous cell carcinoma Esophageal cancer is the seventh most common cancer in Korea, with almost 400,000 new patients diagnosed annually worldwide. There are large variations in the predominant histological type throughout the world but the majority of worldwide esophageal cancers are squamous cell carcinoma arising from the upper and middle thirds of the esophagus. Esophageal cancer is a highly virulent disease with a five-year survival rate of 10-15% . Metastatic esophageal carcinoma is an incurable disease with median survival duration of 6 to 8 months .

   1.2 5-FU plus Cisplatin (FP) combination chemotherapy Cytotoxic chemotherapy has been used to control tumor growth, improve quality of life and prolong survival although a survival advantage for chemotherapy over best supportive care alone in patients with metastatic cancer of the esophagus has not been proven in randomized trials. Although there is no standard chemotherapy regimen for metastatic esophageal cancer, various kinds of chemotherapy regimens have been used to alleviate symptoms caused by cancer and prolong survival and improve quality of life. Various phase-II trials have been performed to evaluate the effect of such chemotherapy. The activity of conventional single agent chemotherapy has been studied for cisplatin, 5-FU and mitomycin, which induced response rates of 15-30% . In most of these studies, the chemotherapy regimen consisted of a combination of cisplatin with another agent such as 5-FU or etoposide for both squamous cell carcinoma and adenocarcinoma. The most commonly used chemotherapy regimen for patients with advanced esophageal cancer is a combination of 5-FU and cisplatin, with response rates ranging from 15% to 45%, however, the effect on survival remained undetermined.

   1.2 Capecitabine for esophageal cancer Capecitabine is a novel, orally administered fluoropyrimidine carbamate that is absorbed readily by the gastrointestinal tract and is metabolized by the liver, where it is converted initially to 5 -deoxy-5-fluorocytidine (5 -DFCR) and subsequently, to 5 -deoxy-5-fluorouridine (5 -DFUR). Designed to mimic continuous intravenous (CIV) 5-FU, oral capecitabine predominantly concentrates in tumor tissue . Capecitabine currently is approved as a single agent for the adjuvant treatment of stage III colon cancer, as first-line treatment for metastatic colorectal cancer, and for metastatic breast cancer both as a single agent for patients and in combination with docetaxel. Whether oral fluoropyrimidines may be appropriately substituted, therefore making the therapy less burdensome to the patient and reducing the need for infusion catheters, is not fully investigated In patients with advanced esophagogastric cancer, capecitabine combinations have generally shown good antitumor activity and highlight the potential of capecitabine as a replacement of infusional 5-FU . Capecitabine has been investigated in combination with cisplatin and docetaxel in phase II trials in patients with advanced esophageal cancer with observed response rates of 47.1% and 46%, respectively . In a recent phase III trial comparing the efficacy of capecitabine/cisplatin (XP) versus FP in advanced gastric cancer, XP was not inferior to FP, in terms of progression-free survival (PFS), overall survival (OS), and response rate (RR) . In our experience, the combination of capecitabine and cisplatin for esophageal cancer showed encouraging response rate (59%) with tolerable toxicities and convenience.

   1.3 Paclitaxel for esophageal cancer Paclitaxel in combination with cisplatin has shown favorable results for advanced esophageal carcinoma . A recent phase II study of bi-weekly administration of paclitaxel and cisplatin in 51 patients resulted in complete response in 4%, partial response in 39%, stable disease in 43% and progressive disease in 14% of patients, and a one-year survival of 43% . Several phase II trials have assessed combinations of taxanes (paclitaxel and docetaxel) and cisplatin and other agents, with response rates of 40-56% .

   1.4 Capecitabine plus Paclitaxel combination for esophageal cancer Capecitabine in combination with docetaxel has greater efficacy than single-agent docetaxel; the combination increased survival significantly compared with single-agent docetaxel (14.5 v 11.5 months) in patients with metastatic breast cancer who experienced disease progression after anthracycline therapy . The most common treatment-related adverse events (TRAEs), with capecitabine 1,250 mg/m2 bid and docetaxel 75 mg/m2 were alopecia, hand-foot skin reaction (HFS), nausea, and fatigue. Neutropenia (15%) and HFS (11%) were the only grade 3 or 4 TRAEs that occurred in more than 10% of patients. In this trial the tolerable delivered dose of capecitabine for most patients was 950 mg/m2 bid for 14 days. Lorenzen et al. treated 24 patients with capecitabine at a dose of 1000 mg/m2 twice daily on Days 1 through 14 and docetaxel 75 mg/m2 on Day 1 of 3-week cycles. The RR was 46% and median survival was 15.8 months. However, the toxicity profile was high with two 2 treatment-related deaths, a high incidence of Grade 3 or 4 neutropenia (42%), and a high incidence of Grade 3 HFS (29%).

   There is a theoretical advantage to using paclitaxel on a weekly schedule in conjunction with capecitabine based on the duration of the upregulation of thymidine phosphorylase (dThPase) by paclitaxel in model systems. The metabolism of capecitabine to the active agent, FU, provides insight into the rationale for combining capecitabine with taxanes in this phase II study . The rationale for combining paclitaxel with capecitabine is based on the upregulation of dTHPase, which has been demonstrated in a model of athymic mice bearing capecitabine-resistant human colon cancer xenografts. Treatment with paclitaxel led to a 7.9-fold increase in intratumoral dThPase. An increase in dThPase activity occurred 4 days after treatment with paclitaxel and persisted for 10 days . These data led to the current concept for this clinical trial, using paclitaxel on days 1 and 8 during a 14-day exposure to capecitabine in patients with MBC. Moreover, these agents have nonoverlapping toxicities and therefore can be combined with reasonable tolerability. It was anticipated that by allowing a week off from weekly paclitaxel therapy, the frequency of sensory neuropathy could be reduced.

   Given the high degree of efficacy of the docetaxel/capecitabine combination, but the significant toxicity observed with 1,250 mg/m2 bid capecitabine schedule, as well as the promising efficacy and safety observed with weekly paclitaxel/capecitabine in the phase I study by Uhlmann et al \[27\], we choose weekly paclitaxel for combination regimen with capecitabine. Practically, our study regimen is capecitabine plus paclitaxel(XT) combination chemotherapy.

   1.5 XP vs XT for esophageal cancer Based on the rationale and our experience, we are going to conduct randomized phase II trial for metastatic esophageal cancer to evaluate the efficacy and feasibility comparing XP with XT.
2. Study Objectives

2.1 Primary Objective: To evaluate response rate for each treatment group (XP vs XT) for metastatic esophageal cancer.

2.2 Secondary Objectives:

1. toxicity
2. progression-free survival
3. quality of life
4. overall survival
5. predictive marker study influencing response and survival

3. Study Design 3.1 Randomization

1. Timing of randomization: Randomization will be performed after inclusion of the patient
2. Stratification factor: performance status (ECOG 0, 1 vs 2) \& weight loss of 10% or more

3.2 Overview of Study Design This study is a prospective, randomized, phase II study comparing response rate between patients with XP chemotherapy versus XT chemotherapy for patients with metastatic squamous cell carcinoma.

Chemotherapy regimen (XP):

D1- D14 Capecitabine 1000 mg/m2 bid p.o. D1 Cisplatin 75 mg/m2 + NS 150mL MIV over 1hr Pre \& Post medication D0 N/S 1500 mL IV overnight hydration D1 DNK2 1000 mL IV over 2 hours, pre \& post hydration (if Mg \< WNL, mix MgSO4 1 amp) 5-HT3 antagonist 1 amp + dexamethasone 20 mg + D5W 100 mL MIV 20% Mannitol 70 mL IV full dripping, 30 mins before cisplatin D2-D5 5-HT3 antagonist 1T QD D2-D3 Dexamethasone 8 mg PO bid D4-D5 Dexamethasone 4 mg PO bid every 3 weeks

Chemotherapy regimen (XT):

D1- D14 Capecitabine 1000 mg/m2 bid p.o. D1, D8 Paclitaxel 80 mg/m2 + D5W 500mL MIV over 3hrs Pre \& Post medication D1, D8 Solucortef 100 mg IV push before Paclitaxel Avil 1A + D5W 50mL MIV 30mins before Taxol Ranitidine 50mg IV + D5W 50mL MIV 30mins before Paclitaxel HT3 antagonist 1A + D5W 50 mL MIV 30mins before Paclitaxel Followed by 1 week off every 3 weeks

3.3 Study Duration and Dates The duration of this study is expected to be 36 months, with subject recruitment proposed to start in October 2008. The actual overall study duration or subject recruitment period may vary.

3.4 Number of Patients/Assignment to Treatment Groups 94 patients will be recruited in total. Patients will be randomized to a treatment arm by permutated method. Chemotherapy should be started within 14 days after randomization.

Efficacy Comparison Study of Combination Regimens to Treat Advanced Esophageal Squamous Cell Carcinoma

A Randomized Phase II Trial of Capecitabine Plus Cisplatin (XP) Versus Capecitabine Plus Paclitaxel (XT) as a First-line Treatment for Advanced or Recurrent Esophageal Squamous Cell Carcinoma

Samsung Medical Center

professor

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Fluorouracil

Irinotecan

Irinotecan 180 mg/m2 I.V 30-90 min，D1；

LV 400 mg/m2 I.V.，D1；

5-FU 400 mg/m2 IVP，d1,1200 mg/m2/d×2 days（Total:2400 mg/m2，Continuous intravenous infusion,46\~48 hours,）

Repeat Every 14 days

Oxaplatin 85 mg/m2 I.V 120 min，D1；

LV 400 mg/m2 I.V.，D1；

5-FU 400 mg/m2 IVP，d1,1200 mg/m2/d×2 days（Total:2400 mg/m2，Continuous intravenous infusion,46\~48 hours,）

Repeat Every 14 days

FOLFIRI as first line chemotherapy versus mFOLFOX6 after adjuvant chemotherapy

FOLFIRI

Ying Yuan, MD,PHD

Ying Yuan, Ph.D & MD

Ying Yuan

A multicenter,open,prospective randomized controlled trial;11 study center in China; Plan to enroll 328 patients（ Power Analysis and Sample Size ）.Comparing FOLFIRI with mFOLFOX6,Superiority design.Investigate difference PFS,ORR,R0 resection rate,OS ,QoL and Safety from two regimens Stratification factors : Analyzing patients recurrence within 6-12months,and 12-18months .Obtain definite chemotherapy regimen shift opportunity for patients recurrence/metastasis after adjuvant chemotherapy.

mFOLXOX6 Versus FOLFIRI for Colorectal Patients Recurrence After Oxaplatin Based Adjuvant Chemotherapy

mFOLXOX6 Versus FOLFIRI for Colorectal Patients Recurrence After Oxaplatin Based Adjuvant Chemotherapy（NEW RECHALLENGE）- A Multicenter Open Prospective Randomized Controlled Trial

Second Affiliated Hospital, School of Medicine, Zhejiang University

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Bevacizumab

Docetaxel

Pirkko-Liisa I Kellokumpu-Lehtinen, MD

The purpose of this study is to evaluate the efficacy and safety of the combination of biweekly docetaxel and bevacizumab in the first line treatment of metastatic breast cancer by using Response Evaluation Criteria In Solid Tumors (RECIST criteria) and NCI Common Terminology Criteria for Adverse Events (NCI CTC-AE) version 3. In addition several biochemical makers are tested as possible predictive factors.

Patients with histologically or cytologically proven measurable or nonmeasurable metastatic breast cancer are treated with a combination of biweekly docetaxel and bevacizumab as the first line treatment in multicenter phase II trial. The outcome measures would be PFS, Response rate (RECIST), duration of response, safety (NCI CTC-AE version 3) and survival. In addition several biochemical makers are tested as possible predictive factors. Treatment would be continued until PD, patient's refusal or treatment discontinuation due to side-effects or patients death. In responding patients bevacizumab would be continued either alone or in hormone receptor positive patients combined with hormone treatment until progression.

Biweekly Avastin and Docetaxel as the First Line Treatment for Patients With Metastatic Breast Cancer

Single Arm Study of the Combination of Biweekly Avastin and Docetaxel as the First Line Treatment for Patients With Metastatic Breast Cancer

side effects according to NCICTC-AE version 3.0

Oulu University Hospital

Turku University Hospital

Tampere University Hospital

professor of oncology and radiotherapy

Triple Negative Breast Neoplasms

Gemcitabine

GP (gemcitabine and cisplatin combination)

Eribulin 1.4mg/m2, IV , D1, D8；Cisplatin 75 mg/m2, IV，D1

Eribulin,cisplatin

Gemcitabine 1250 mg/m2, IV , D1, D8； Cisplatin 75 mg/m2, IV, D1

Gemcitabine,cisplatin

Jian Zhang, MD,PhD

Yiqun Du, MD,PhD

Eribulin Plus Cisplatin Versus Gemcitabine Plus Cisplatin in Triple Negative Breast Cancer (TNBC)

A Phase II, Single-center, Randomized Study of Eribulin Plus Cisplatin (EP) Versus Gemcitabine Plus Cisplatin (GP) as First-Line Treatment in Patients With Advanced Triple-Negative Breast Cancer.

A Phase II, Single-center, Randomized Study of Eribulin Plus Cisplatin (EP) Versus Gemcitabine Plus Cisplatin (GP) as First-Line Treatment in Patients With Advanced Triple-Negative Breast Cancer

Fudan University

Associate chief physician

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Adenocarcinoma

Adenocarcinoma of Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Lung Adenocarcinoma

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Treatment with previous regimen of combined chemotherapy

Adding bevacizumab to the previous regimen of combined chemotherapy

The patients in conventional group continued the previous chemotherapy,and the patients in experimental group received adding bevacizumab to previous chemotherapy regimen.

bevacizumab

Bin Ai, Docter

Xu Li, Master

Yixin Zeng, Doctor

Previous studies have shown that the addition of bevacizumab to the standard first-line platinum-based combination therapy can improve the objective response rate of patients with advanced non-squamous non-small cell lung cancer by 20% to 28% and improve survival. Data from these published literatures suggest that the improvement in objective response rates is due mainly to patients with stable disease of chemotherapy. It has been reported that 15% of patients achieved objective remission after continuing treatment with the regimen after receiving 2 cycles of platinum-based combination chemotherapy. Therefore, the use of 2 cycles of chemotherapy after stabilization of patients with bevacizumab, hoping to improve the objective response rate of such patients 20%, and may improve survival. For the above reasons, design this study to validate our hypothesis.

Previous studies have shown that the addition of bevacizumab to the standard first-line platinum-based combination therapy can improve the objective response rate of patients with advanced non-squamous non-small cell lung cancer by 20% to 28% and improve survival. Data from these published literatures suggest that the improvement in objective response rates is due mainly to patients with stable disease of chemotherapy. It has been reported that 15% of patients achieved objective remission after continuing treatment with the regimen after receiving 2 cycles of platinum-based combination chemotherapy. Therefore, the use of 2 cycles of chemotherapy after stabilization of patients with bevacizumab, hoping to improve the objective response rate of such patients 20%, and may improve survival. For the above reasons, design this study to validate our hypothesis.

So a prospective cohort study has been designed to confirm this hypothesis, patients with advanced pulmonary adenocarcinoma who are stable after two cycles of platinum-based combination chemotherapy are objects of this study, and they can choose to continue the previous treatment regimen according to the guideline or adding bevacizumab to the regimen independently until the progression or intolerance of toxicity, or 4 to 6 cycles of chemotherapy in stable disease. The objective response rate in these two groups who received different treatment is the primary endpoint and the toxicity, quality of life, the progression free survival are the second endpoints.

Effectiveness and Safety of Adding Bevacizumab to First Line Chemotherapy in Lung Cancer Patients With Stable Disease

Effectiveness and Safety of Adding Bevacizumab to Chemotherapy in Patients With Advanced Lung Adenocarcinoma With Stable Disease After 2 Cycles of First Line Combination Chemotherapy: a Multicenter, Prospective Cohort Study

The percentage of patients who was assessed as complete response and partial response according RECIST (Response Evaluation In Solid Tumors).

The duration in responsive patients from the first remission to the progression.

The time from the day written consent to the first date of objective progression or death from any cause.

The adverse effects of the treatment especially in hematology,cardiovascular system and renal system according the CTCAE 4.0, and the SAE(serious adverse events) in the treatment and follow up.

The quality of life should be assessed in the study using FACT-L(Functional Assessment of Cancer Therapy - Lung).

Beijing Hospital

Deputy chief physician

Neoplasm Metastasis

Squamous Cell Carcinoma of Head and Neck

Neoplastic Processes

Cetuximab

Lenograstim

Patients receive four cycles of chemotherapy comprising cetuximab IV plus docetaxel IV over 1 hour and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of the fourth cycle of chemotherapy, patients receive a maintenance therapy with cetuximab every 2 weeks. Treatment will be continued until disease progression or unacceptable toxicities according

* Cetuximab 400 mg/m² over 120 minutes on day 1 of cycle 1 only.
* Cetuximab dose will be 250 mg/m² IV over 60 minutes weekly on subsequent administrations during the four cycles of chemotherapy.
* Cetuximab dose will be 500mg/m2 IV every 2 weeks during the maintenance therapy.

Drug: Cisplatin IV : 75 mg/m2 intravenous every 3 weeks for 4 cycles

Drug: Docetaxel IV : 75 mg/m2 intravenous every 3 weeks for 4 cycles

G-CSF support with lenograstim 150 microg./m2/day is delivered after each cycle of chemotherapy.

cetuximab IV

No intervention, only biopsy for translational project.

Biopsies

Joel GUIGAY

PURPOSE: Cetuximab with platinum and 5FU is now the standard combination as first-line treatment in patients with metastatic or recurrent Head and Neck squamous cell carcinomas. Cetuximab and taxane combinations have demonstrated promising activity in Head and Neck cancer. This phase II trial is studying new cetuximab, docetaxel and cisplatin combination named TPEx as first-line treatment in this setting.

OBJECTIVES:

Primary

* To determine the efficacy of TPEx combination in patients with head and neck cancer in term of objective response rate (RECIST, see statistical consideration) Secondary
* To assess toxicities of TPEx combination
* Determine the efficacy of TPEx combination in patients with head and neck cancer: Best Overall Response , progression-free survival and survival.
* Translational research objective:To better understand the mechanisms of chemoresistance and to identify biomarkers by the analysis of the tumor biopsies (RNA, gene expression profile) and protein profile (plasma samples). Exploratory analyses.

OUTLINE: This is an open-label phase II, multicenter study. Patients receive four cycles of chemotherapy comprising cetuximab IV plus docetaxel IV over 1 hour and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of the fourth cycle of chemotherapy, patients receive a maintenance therapy with cetuximab every 2 weeks. Treatment will be continued until disease progression or unacceptable toxicities according to the patient or the investigator. Tumor check-up will be performed every 6 weeks. This study will allow translational research with blood sample and biopsies at baseline before any treatment, during the treatment with TPEx combination (week 6).,After completion of study treatment, patients are followed every 2 months.

Chemotherapy With Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Phase II Study of Cetuximab, Docetaxel and Cisplatin as First-line Treatment in Patients With Metastatic or Recurrent Head and Neck Squamous Cell Carcinomas - GORTEC 2008-03 TPEx

The objective tumor response rate is evaluated every 6 weeks according to RECIST criteria.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT-scan or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.

All grade 1 to 5 toxicity are registered during treatment. Patients have weekly clinical and biological examination.

Tumor response is evaluated every 6 weeks according to RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions, Stable Disease (SD); Best overall Response = CR + PR + SD.

Gustave Roussy, Cancer Campus, Grand Paris

Groupe Oncologie Radiotherapie Tete et Cou

Patients receive four cycles of chemotherapy comprising cetuximab IV plus docetaxel IV over 1 hour and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of the fourth cycle of chemotherapy, patients receive a maintenance therapy with cetuximab every 2 weeks. Treatment will be continued until disease progression or unacceptable toxicities according cetuximab IV: - 400 mg/m² over 120 minutes on day 1 of cycle 1 only.

* 250 mg/m² IV over 60 minutes weekly on subsequent administrations during the four cycles of chemotherapy.
* 500mg/m2 IV every 2 weeks during the maintenance therapy.

Drug: Cisplatin IV : 75 mg/m2 every 3 weeks for 4 cycles Drug: Docetaxel IV : 75 mg/m2 every 3 weeks for 4 cycles

G-CSF support with lenograstim 150 microg./m2/day is delivered after each cycle of chemotherapy.

Biopsies: No intervention, only biopsy for translational project.

Age, Categorical

Age, Continuous

Sex: Female, Male

Belgium

France

Region of Enrollment

Pr. Joël GUIGAY

Patients receive four cycles of chemotherapy comprising cetuximab IV plus docetaxel IV over 1 hour and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of the fourth cycle of chemotherapy, patients receive a maintenance therapy with cetuximab every 2 weeks. Treatment will be continued until disease progression or unacceptable toxicities according

cetuximab IV: - 400 mg/m² over 120 minutes on day 1 of cycle 1 only.

* 250 mg/m² IV over 60 minutes weekly on subsequent administrations during the four cycles of chemotherapy.
* 500mg/m² IV every 2 weeks during the maintenance therapy. Drug: Cisplatin IV : 75 mg/m² every 3 weeks for 4 cycles Drug: Docetaxel IV : 75 mg/m² every 3 weeks for 4 cycles

G-CSF support with lenograstim 150 microg/m²/day is delivered after each cycle of chemotherapy.

Biopsies: No intervention, only biopsy for translational project.

Objective Tumor Response Rate

Grade 1 to 5 Toxicity

2 patients not assessable for response at 12 weeks

Best Overall Response

Progression-free Survival

Overall Survival

Biomarkers

cetuximab IV: - 400 mg/m² over 120 minutes on day 1 of cycle 1 only.

* 250 mg/m² over 60 minutes weekly on subsequent administrations
* 500mg/m2 every 2 weeks during the maintenance therapy. Drug: -Cisplatin IV : 75 mg/m2 every 3 weeks for 4 cycles
* Docetaxel IV : 75 mg/m2 every 3 weeks for 4 cycles G-CSF support mandatory after each cycle of chemotherapy. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of the 4th cycle of chemotherapy, patients receive a maintenance therapy with cetuximab every 2 weeks.

Overall Study

Trastuzumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.

BKM120 placebo in combination with trastuzumab and paclitaxel

Neo-adjuvant BKM120 (oral pan-class I PI3K inhibitor, continuous daily dosing). BKM120 was administered orally 100 mg/day.

BKM120

Trastuzumab is a humanized monoclonal antibody directed against the extracellular juxtamembrane domain of the HER2 receptor. Administered 4mg/kg i.v. load followed by 2mg/kg i.v. weekly.

Paclitaxel is a cytotoxic agent with proven antitumor activity in a variety of solid tumors. The antitumor activity of paclitaxel is based on tubulin-binding and stabilization of non-functional microtubule bundles, thereby blocking normal mitotic spindle development and subsequent cell division. Administered weekly 80mg/m2 i.v.

Neoadjuvant BKM120 placebo Administered orally 100 mg/day.

BKM120 Placebo

Novartis Pharmaceuticals

This randomized, parallel cohort, two stage, double-blind, placebo-controlled study evaluated the oral PI3K inhibitor BKM120 in combination with trastuzumab and paclitaxel in HER2-positive, PIK3CA wild-type and PIK3CA mutant primary breast cancer prior to surgery (neo-adjuvant setting).

NeoPHOEBE evaluated the efficacy (as defined by pCR) of BKM120 (an oral PI3K inhibitor) in combination with trastuzumab and paclitaxel in a randomized, placebo-controlled, neo-adjuvant study in women diagnosed with primary breast cancer \>1.5 cm (by US or MRI) with centrally confirmed HER2 overexpression or amplification, who have not previously undergone treatment for invasive breast cancer.

Prior to the initiation of paclitaxel, there was a 6-week "biologic window" with trastuzumab plus BKM120 or placebo only. The study was conducted separately in two cohorts (PIK3CA mutated and PI3K3CA wild-type) using a two-stage approach. Within each cohort patients were randomized into one of the following treatment arms:

Arm 1: BKM120 plus trastuzumab for 6 weeks followed by BKM120 and trastuzumab plus weekly paclitaxel for an additional 12 weeks.

Arm 2: BKM120 placebo plus trastuzumab for 6 weeks followed by BKM120 placebo plus trastuzumab plus weekly paclitaxel for an additional 12 weeks.

After completion of study treatment, patients were to have undergone definitive surgery.

NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer

NeoPHOEBE: Pi3k Inhibition in Her2 OverExpressing Breast cancEr: A Phase II, Randomized, Parallel Cohort, Two Stage, Double-blind, Placebo-controlled Study of Neoadjuvant Trastuzumab Versus Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive, PIK3CA Wild-type and PIK3CA Mutant Primary Breast Cancer

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast \[ypT0\]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.

Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.

Rate of patients with breast conserving surgery. Participants who did not have breast surgery were also considered as having breast conservation surgery (BCS)

Rate of pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 \[GBG definition\]). If patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to NSABP guidelines.

Rate of pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 \[MD Anderson definition\]). If a patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions.

Number of Overall objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.

pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 \[GBG definition\]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 \[MD Anderson definition\]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions.

Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.

This included participants at definitive surgery irrespective of lymph node status

Node-negative disease at definitive surgery (ypN0) were considered as binary variables of 'response' versus 'non response'.

Breast International Group

German Breast Group

SOLTI Breast Cancer Research Group

All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.

Trastuzumab + BKM120 + Paclitaxel

Trastuzumab + BKM120 PBO + Paclitaxel

Total

Caucasian/white

Asian/Oriental

Other

Race/Ethnicity, Customized

All randomized patients (N=50) were included in the intention-to-treat set and in the safety analysis set, since all patients started study treatment. Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization.

Study Director

Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy Comparison Study of Combination Regimens to Treat Advanced Esophageal Squamous Cell Carcinoma	NCT00816634	First Line Chem... Capecitabine Pl... Advanced or Rec...	Capecitabine pl...	18 Years -	Samsung Medical Center
mFOLXOX6 Versus FOLFIRI for Colorectal Patients Recurrence After Oxaplatin Based Adjuvant Chemotherapy	NCT05362617	Metastatic Colo...	FOLFIRI	18 Years - 75 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
Biweekly Avastin and Docetaxel as the First Line Treatment for Patients With Metastatic Breast Cancer	NCT00979641	Neoplasms	Docetaxel	18 Years -	Tampere University Hospital
Eribulin Plus Cisplatin Versus Gemcitabine Plus Cisplatin in Triple Negative Breast Cancer (TNBC)	NCT04517292	Breast Cancer	Eribulin,cispla... Gemcitabine,cis...	18 Years - 70 Years	Fudan University
Effectiveness and Safety of Adding Bevacizumab to First Line Chemotherapy in Lung Cancer Patients With Stable Disease	NCT03240549	Non-small Cell ...	bevacizumab	18 Years - 75 Years	Beijing Hospital
Chemotherapy With Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer	NCT01289522	Squamous Cell H... Recurrent or Me...	cetuximab IV Biopsies	18 Years - 70 Years	Groupe Oncologie Radiotherapie Tete et Cou
NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer	NCT01816594	HER2-positive N...	BKM120 Trastuzumab Paclitaxel BKM120 Placebo	18 Years -	Novartis
NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer	NCT01816594	HER2-positive N...	BKM120 Trastuzumab Paclitaxel BKM120 Placebo	18 Years -	Novartis
Eribulin Plus Cisplatin Versus Gemcitabine Plus Cisplatin in Triple Negative Breast Cancer (TNBC)	NCT04517292	Breast Cancer	Eribulin,cispla... Gemcitabine,cis...	18 Years - 70 Years	Fudan University
Chemotherapy With Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer	NCT01289522	Squamous Cell H... Recurrent or Me...	cetuximab IV Biopsies	18 Years - 70 Years	Groupe Oncologie Radiotherapie Tete et Cou
Effectiveness and Safety of Adding Bevacizumab to First Line Chemotherapy in Lung Cancer Patients With Stable Disease	NCT03240549	Non-small Cell ...	bevacizumab	18 Years - 75 Years	Beijing Hospital

Spots Global Cancer Trial Database for first line chemotherapy