Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Uterine Neoplasms

Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

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

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Tubulin Modulators

Antimitotic Agents

Carboplatin AUC

Abraxane

Franco Muggia, MD

The purpose of this study is to evaluate the safety of treatment with carboplatin and Abraxane in this patient population and determine the nature and degree of toxicities following treatment. The single stage open label Phase II feasibility study is designed to estimate the proportion of patients who can tolerate the proposed regimen for 6 cycles with no more than two dose level reductions.

A Phase 2 Feasibility Study of Abraxane and Carboplatin in Epithelial Neoplasms of the Uterus

Tolerability for an individual patient will be defined as remaining on the study for 6 cycles with two or fewer dose reductions.

PFS is defined as the time from first dosing to the first observation of disease progression or death due to any cause. PFS was estimated beyond the collected data using Kaplan Meier methods.

ORR is the number of patients whose best tumor response outcome by Month 24 is a Complete Response (CR) or Partial Response (PR), divided by the total number of evaluable patients.

Per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1.):

CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD

NYU Langone Health

Carboplatin AUC and Abraxane 100mg/m2

Approximately 23 patients will be enrolled in this study at the Laura \& Isaac Perlmutter Cancer Center at NYU Langone.There is a total of 17 study visits, including the screening visit to determine if you are eligible to participate. This study will be an out-patient study.

Age, Continuous

Female

Sex/Gender, Customized

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

1-MD Decision

1. Drug toxicity
2. progressive disease

Tolerability Measured Completion of Dose Regimen

Progression-Free Survival (PFS) at Month 24

Objective Response Rate (ORR) as Measured by RECIST 1.1 at Month 24

Overall Study

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Recurrence

Adenocarcinoma

Esophageal Neoplasms

Carcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Amino Acids

Lapatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Carboplatin AUC 6 IV over 30 minutes on day one of a three week cycle. This will be continued for 6 cycles or until progression of disease or intolerable side effects.

Paclitaxel 175 mg/m2 IV over 3 hours day one of a three week cycle. This will be continued for 6 cycles or until progression of disease or intolerable side effects.

Lapatinib should be taken once daily, at the same time daily, on an empty stomach, either 1 hour before, or 1 hour after meals.

lapatinib

David Adelstein, MD

Neelesh Sharma, MD

RATIONALE: Since lapatinib inhibits both EGFR and HER2 receptors, it is an attractive agent for the treatment of esophageal and GEJ tumors.

PURPOSE: Lapatinib is currently approved for HER2 positive metastatic breast cancer in combination with capecitabine or letrozole. It is hoped that by giving lapatinib and carboplatin and paclitaxel together, their combined effects will further slow or stop the cancer cells from growing.

OBJECTIVES:

1. Phase I: To assess the toxicity and feasibility of the addition of lapatinib to carboplatin and paclitaxel in patients with recurrent/metastatic adenocarcinoma of the esophagus and gastroesophageal junction.
2. Phase II: To assess the response rate to this regimen.

OUTLINE:

1. There will be an initial phase I safety cohort studies requiring up to 12 patients, followed by a phase II cohort using the lapatinib dose defined in phase I. Carboplatin and paclitaxel doses will not be escalated.

   The initial dose of lapatinib of 750 mg daily by mouth will be given to 6 patients. There will be no dose escalation of the lapatinib above 1000 mg daily. The lapatinib dose for the phase II cohort of this trial will be based only on toxicities experienced during the first cycle (3 weeks) of treatment.
2. Phase II: Once the optimal lapatinib dose has been chosen, all remaining patients will initiate treatment at this dose level. Patients with stable or responding disease after 6 cycles will continue treatment with lapatinib alone until progression of disease or intolerable side effects. Feasibility, toxicity and response rate of this combination will be assessed.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Lapatinib With Carboplatin and Paclitaxel in Esophagus and Gastroesophageal Junction (GEJ)

Phase I/II Pilot Study of Lapatinib in Combination With Carboplatin and Paclitaxel in the Treatment of Recurrent/Metastatic Adenocarcinoma of the Esophagus and Gastroesophageal Junction (GEJ)

A dose limiting toxicity (DLT) will be defined as any grade 3-4 non-hematologic toxicity or increase in bilirubin \>/= 2 mg/dL (\>2X baseline in patients with Gilbert's syndrome), or elevation in AST/ALT \> 3.0 X ULN during the first 3 week course of therapy.

Number of patients with stable or responding disease after 6 cycles of carboplatin and paclitaxel will continue treatment with lapatinib alone until progression of disease or intolerable side effects.

Overall survival is defined as the length of time between the date of starting treatment and death due to any cause. For a patient who is alive at the time of the statistical analysis, the patient will be considered censored at the last date of known contact.

Case Comprehensive Cancer Center

Carboplatin AUC: Carboplatin AUC 6 IV over 30 minutes on day one of a three week cycle. This will be continued for 6 cycles or until progression of disease or intolerable side effects.

Paclitaxel: Paclitaxel 175 mg/m2 IV over 3 hours day one of a three week cycle. This will be continued for 6 cycles or until progression of disease or intolerable side effects.

lapatinib: Lapatinib should be taken once daily, at the same time daily, on an empty stomach, either 1 hour before, or 1 hour after meals.

Lapatinib With Carboplatin and Paclitaxel

Sex: Female, Male

One patient was treated in phase II cohort. The study was then prematurely terminated because of the results of the TRIO-013/LOGiC trial. It failed to meet its primary survival endpoint, suggesting little justification for continuation of our study.

David Adelstein MD

PHASE I: Number of Patients That Experience a Grade 3-4 Dose Limiting Toxicity

Participants eligible to move to phase II of study. Study was cancelled prior to additional participants moving to study.

PHASE II: To Assess the Response Rate to This Regimen.

To Determine the Overall Survival

Phase I

Phase II

Skin and Connective Tissue Diseases

Diseases and Abnormalities at or Before Birth

Breast Neoplasms

Wilms Tumor

Breast Diseases

Skin Diseases

Wilms' Tumor

Antirheumatic Agents

Natriuretic Agents

Anti-Infective Agents

Docetaxel

Trastuzumab

Fluorouracil

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Hormones

Exemestane

Letrozole

Epirubicin

Immunomodulating Agents

Mannitol

Mitogens

Aromatase Inhibitors

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antimetabolites

Antineoplastic Agents, Immunological

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.

This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.

This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of GSK2302024A, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

This group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

6 or 8 injections at 3 weeks apart, injected intramuscularly in the deltoid or lateral region of the thigh.

GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A

6 or 8 doses at 3 weeks apart of sucrose/mannitol-based formulation reconstituted with an oil-in-water emulsion, injected intramuscularly in the deltoid or lateral region of the thigh.

Placebo

This treatment consisted of any aromatase inhibitor (e.g. letrozole or exemestane), administered intravenously in Cohort A Groups daily for either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).

Aromatase inhibitor

Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

5-Fluorouracil

Administered intravenously in Cohort C Groups in 6 doses at 3 weeks apart, on the same day as WT1 ASCI/placebo administration (Day 1 of each cycle).

Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

Administered intravenously in Cohort C Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

GSK Clinical Trials

The purpose of this study is to evaluate the safety, immunogenicity and clinical activity of a new WT1 anti-cancer immunotherapy in patients with WT1-positive Stage II or III breast cancer. The treatment will be given before surgery in combination with standard therapy.

The study will be conducted in two consecutive segments (Phase I and Phase II), each with specific objectives. Active follow-up will be for three years.

Patients in this study will be allocated to cohorts as below. Cohort A will include postmenopausal patients with hormone receptor-positive breast cancer who receive aromatase inhibitor (AI) as neoadjuvant therapy concurrently with administration of 6 or 8 doses of WT1 anti-cancer immunotherapy (WT1 ASCI)/placebo starting on Day 0. AI treatment will be administered daily for duration of either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).

Cohort B will include breast cancer patients who will receive neoadjuvant chemotherapy concurrently with administration of WT1 ASCI/placebo starting on Day 0. Neoadjuvant chemotherapy in Cohort B will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly or 12-weekly taxane administrations without trastuzumab.

Cohort C will include patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who will receive neoadjuvant trastuzumab (Herceptin) therapy combined with chemotherapy concurrently with administration of WT1 ASCI/placebo starting on Day 0. Neoadjuvant chemotherapy in Cohort C will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly or 12-weekly taxane administrations with trastuzumab.

Cohorts D and E will include patients with hormone receptor-positive and HER2 non-overexpressing breast cancer who will receive neoadjuvant chemotherapy. For patients in these Cohorts D and E, WT1 ASCI/placebo (placebo applicable only for Cohort E patients) will be administered on Day 14 of each three-weekly cycle of chemotherapy. Neoadjuvant chemotherapy in Cohorts D and E will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly taxane administrations without trastuzumab. Enrolment in Cohort E will be conditional on the absence of a safety signal and on the adequate induction of an immune response by the WT1 ASCI in Cohort D (defined as \>= 40% response rate based on post-Dose 4 anti-WT1 antibody responses in at least six patients). If this criterion is met, 60 patients (40 receiving WT1 ASCI and 20 placebo) with identical eligibility criteria will be enrolled into Cohort E. In case no adequate safety and/or immunogenicity will be obtained in Cohort D, recruitment in Cohort E will not be initiated.

The protocol has been updated following Protocol Amendment 4, April 2013, leading to the update of the study design.

Evaluation of an Anti-cancer Immunotherapy Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer

Study of GSK2302024A Antigen-Specific Cancer Immunotherapeutic Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer

IPD for this study is available via the Clinical Study Data Request site (click on the link provided below).

Severe toxicity was defined as follows: - A Grade 3 or higher toxicity that is related or possibly related to the combined administration of standard treatment and GSK2302024A/placebo - A decrease in Left Ventricular Ejection Fraction (LVEF) from baseline with ≥ 10 points and at \< 50% that is related or possibly related to the combined administration of treatment and that is confirmed by a second LVEF assessment within approximately 3 weeks. - A Grade 2 or higher cardiac ischemia/infarction that is related or possibly related to the combined administration of standard treatment and GSK2302024A /placebo. - A Grade 2 or higher allergic reaction occurring within 24 hours following the administration. - A Grade 3 or higher blood/bone marrow toxicity that was considered as related or possibly related to the combined Administration. - A decrease in renal function at the time of administration that was considered as related or possibly related.

For initially seronegative patients: post-administration antibody concentration ≥ 9 EU/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-administration antibody concentration.

An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.

A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, causes disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient. In this study, an event which was part of the natural course of the disease under study (i.e., disease progression/recurrence) was captured in the study/as an efficacy measure. Therefore it was not reported as an SAE. Progression/recurrence of the tumor was recorded in the clinical assessments in the electronic case report form (eCRF). Death due to progressive disease was recorded on a specific form in the eCRF but not as an SAE.

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).

The pathological response in lymph nodes was evaluated by presence or absence of tumor cells by histopathological examination. Partial responses mark the disappearance of tumor cells, with only small clusters or dispersed cells remaining (more than 90% loss) while complete response indicate no identifiable malignant cells. However, ductal carcinoma in situ may be present.

GlaxoSmithKline

Cohort A-GSK2302024A Group

Cohort A-Placebo Group

This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Cohort B-GSK2302024A Group

Cohort B-Placebo Group

Cohort C-GSK2302024A Group

This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule

Cohort C-Placebo Group

Cohort D-GSK2302024A-D14 Group

Total

GSK Response Center

This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Number of Subjects With Severe Toxicities

According-to-Protocol (ATP) Population for immunogenicity included all eligible patients who did not report major protocol deviation, who had at least received the first 4 doses of study product and provided a valid result for immunogenicity measurement within the 4 weeks following Dose 4.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 2 Feasibility Study of Abraxane and Carboplatin in Epithelial Neoplasms of the Uterus	NCT02744898	Endometrial Can...	Carboplatin AUC Abraxane	18 Years -	NYU Langone Health
Lapatinib With Carboplatin and Paclitaxel in Esophagus and Gastroesophageal Junction (GEJ)	NCT01395537	Adenocarcinoma ... Adenocarcinoma ...	Carboplatin AUC Paclitaxel lapatinib	18 Years -	Case Comprehensive Cancer Center
Evaluation of an Anti-cancer Immunotherapy Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer	NCT01220128	Neoplasms, Brea...	GSK Biologicals... Placebo Aromatase inhib... 5-Fluorouracil Carboplatin AUC Cyclophosphamid... Docetaxel Doxorubicin Epirubicin Paclitaxel Trastuzumab	18 Years -	GlaxoSmithKline
Magnetic Resonance-Guided Hypofractionated Adaptive Radiation Therapy With Concurrent Chemotherapy and Consolidation Durvalumab for Inoperable Stage IIB, IIIA, and Select IIIB and IIIC Non-small Cell Lung Cancer	NCT03916419	Stage IIB Non-S... Stage IIIA Non-... Stage IIIB Non-... Stage IIIC Non-...	ViewRay MR-Line... Radiation thera... Paclitaxel Carboplatin AUC Durvalumab	18 Years -	Washington University School of Medicine
Lapatinib With Carboplatin and Paclitaxel in Esophagus and Gastroesophageal Junction (GEJ)	NCT01395537	Adenocarcinoma ... Adenocarcinoma ...	Carboplatin AUC Paclitaxel lapatinib	18 Years -	Case Comprehensive Cancer Center
Magnetic Resonance-Guided Hypofractionated Adaptive Radiation Therapy With Concurrent Chemotherapy and Consolidation Durvalumab for Inoperable Stage IIB, IIIA, and Select IIIB and IIIC Non-small Cell Lung Cancer	NCT03916419	Stage IIB Non-S... Stage IIIA Non-... Stage IIIB Non-... Stage IIIC Non-...	ViewRay MR-Line... Radiation thera... Paclitaxel Carboplatin AUC Durvalumab	18 Years -	Washington University School of Medicine
A Phase 2 Feasibility Study of Abraxane and Carboplatin in Epithelial Neoplasms of the Uterus	NCT02744898	Endometrial Can...	Carboplatin AUC Abraxane	18 Years -	NYU Langone Health

Spots Global Cancer Trial Database for carboplatin auc