Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Adenocarcinoma

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

Hematinics

Vitamins

Docetaxel

Folic Acid

Vitamin B Complex

Vinca Alkaloids

Tubulin Modulators

Antimitotic Agents

Trace Elements

Folinic Acid

Folate

Vitamin B9

2.5 mg on Days 1,4,8,11 (Weeks 1 and 2 q3 weeks)

EC145

EC145 2.5 mg on Days 1,4,8,11 (Weeks 1 and 2 q3 weeks) +

Docetaxel 75 mg/m2 IV Day 1 q 3 weeks

EC145 + Docetaxel

During the screening period participants will receive a single intravenous administration of EC20 prior to SPECT imaging

EC20

Binh Nguyen, MD, PhD

This study will test the activity of single-agent EC145 and the combination of EC145 plus docetaxel against the current standard docetaxel in second line Non Small Cell Lung Cancer (NSCLC) (adenocarcinoma, squamous, adenosquamous or adenocarcinoma with other NSCLC variants of the lung) in participants with all target lesions expressing the folate receptor \[FR(++)\].

In a phase 2 study of single-agent EC145 in heavily pretreated non-small cell lung cancer (NSCLC) patients (median of 3 prior chemotherapy regimens), the subgroup with all target lesions expressing the folate receptor \[FR(++)\] had a promising prolonged progression free survival of 7.1 months and overall survival of 10.9 months. Furthermore, in-vitro and in-vivo studies in KB models showed good synergism between EC145 and docetaxel.

This study will clinically assess for the first time the combination of EC145+docetaxel (Arm B) in participants with NSCLC (Stage IIIB or IV). This is an international, multicenter, centrally randomized, open-label, phase 2 study comparing single-agent EC145, EC145+docetaxel combination therapy, and single-agent docetaxel in participants with NSCLC who have failed one prior chemotherapy and who have all target lesions expressing the folate receptor \[FR(++)\]. Eligible participants will be randomized in a 1:1:1 ratio into either Arm A (single-agent EC145), Arm B (EC145+docetaxel combination therapy), or Arm C (single-agent docetaxel) and will receive treatment until either disease progression or intolerable toxicity.

This study is intended to investigate if there is a sufficiently strong efficacy signal in order to proceed with phase 3 testing with either EC145 single-agent and/or the combination of EC145+docetaxel against the standard-of-care docetaxel in second-line NSCLC.

This study will clinically assess for the first time the combination of EC145+docetaxel (Arm B) in participants with NSCLC (Stage IIIB or IV). Therefore, an interim safety analysis will be done by the DSMB after 5 participants in Arm B have completed 1 cycle of therapy, and the second analysis after 15 participants in Arm B have completed 1 cycle of therapy.

If the majority of the enrolled participants (more than 70%) require a dose reduction of one level (to 60 mg/m2), the dose will be reduced for the remainder of the study. If the majority of the participants (more than 70%) require 2 dose reductions (to 40 mg/m2), the sponsor will consider discontinuing the combination arm.

Phase 2 Study of EC145 Alone Versus EC145+Docetaxel Versus Docetaxel Alone in Participants With FR(++) 2nd Line Non Small Cell Lung Cancer

A Randomized, Open-label Phase 2 Study of EC145 Single-agent and the Combination of EC145 Plus Docetaxel Versus Docetaxel Alone in Participants With Folate-receptor Positive [FR(++)] Second Line NSCLC

Disease assessment will be conducted via CT/ MRI every 6 weeks while on study. Participants who come off study due to any other reason except progression of disease or death will be followed via CT/ MRI every 6 weeks until disease progression or until start of new therapy.

Analysis will occur when approximately 50% of the PFS events have occurred (for each comparison) and when 94 PFS events have occurred.

Analysis will occur when approximately 50% of the PFS events gave occurred (for each comparison) and when 94 PFS events have occurred.

Adverse events (as a measure of safety and tolerability) will be assessed at each study visit.

Endocyte

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

Total Laparoscopic or Robotic Radical Hysterectomy

In a radical hysterectomy the uterus, the upper one to two centimetres of the vagina and the soft tissues around the cervix are excised.

Total Abdominal Radical Hysterectomy

Pedro Ramirez, M.D.

Andreas Obermair, MD

Michael Frumovitz, M.D.

The goal of this clinical research study is to compare the long-term outcomes of different surgical methods for the treatment of cervical cancer. The long-term outcome of a total abdominal radical hysterectomy (TARH) will be compared against laparoscopy. In this study, the laparoscopy will be done with or without robotic technology.

Primary Objective:

To compare disease-free survival amongst patients who undergo a total laparoscopic (TLRH) or robotic radical hysterectomy (TRRH) verses those who undergo a total abdominal radical hysterectomy (TARH) for early stage cervical cancer.

Secondary Objectives:

* Compare patterns of recurrence between arms.
* Compare treatment-associated morbidity within 6 months from surgery.
* Compare the cost effectiveness of TLRH/TRRH versus TARH
* Compare the impact on Quality of Life (QOL) between arms.
* Assess pelvic floor function
* Compare overall survival between arms
* Determine the feasibility of sentinel lymph node biopsy in this group of patients

RATIONALE FOR STUDY DESIGN Total abdominal radical hysterectomy (TARH) and pelvic lymph node dissection (± aortic lymph node dissection ± postoperative \[chemo-\] radiotherapy) is the current standard treatment for early cervical cancer. While this is an accepted effective treatment, a laparotomy is highly invasive, visibly scarring and is associated with tissue trauma, blood loss and a significant risk of wound and infectious adverse events . Additionally, radical hysterectomy by laparotomy is associated with an average hospital stay of approximately 5 to 7 days and an average recovery period (from surgery) of 5 to 6 weeks.

Laparoscopic techniques have been demonstrated to be feasible and safe with previous retrospective studies on TLH showing encouraging results . In a number of retrospective and prospective, non-controlled series the incidence of treatment-related morbidity was less in patients who had a laparoscopic hysterectomy compared to patients who underwent a TAH . Retrospective data suggest that the recurrence rate and patterns of recurrence are similar in patients who had a laparoscopic or an open approach .

Treatment recommendations ideally are based on prospective, randomized trials comparing the current standard technique (TARH) with the proposed better technique (TLRH). However, there are currently no prospective studies available which directly compare TLRH against the standard treatment of TARH in regards to disease-free or overall survival.

The proposed clinical trial will be biphasic. The primary outcome variable in stage 1 will be feasibility of recruitment as determined by overall trial recruitment. Following completion of Stage 1, the data of this study will become the basis for assessing recurrence and disease-free survival in the Stage 2 design.

RATIONALE FOR THE QUALITY OF LIFE Retrospective studies suggest equivalency between the laparoscopic and open approaches to radical hysterectomy in regards to surgical specimens obtained and likely disease-free and overall survivals . Thus, quality of life could be seen as one of the most significant factors in recommending one approach over the other and therefore an extremely important endpoint for this protocol. In the GOG LAP-2 protocol , a trial evaluating a comparison between hysterectomy by laparotomy or laparoscopy, the investigators found equivalency adequacy of the two surgical approaches however a significant difference in short term quality of life favoring laparoscopy. As expected, patients who underwent laparoscopy had a faster return to baseline functioning compared with those patients who had undergone laparotomy which translated into improved short-term quality of life. By 6 months, however, patients in both cohorts were reporting equivalent quality of life parameters. Quality of life surveys employed with this Phase III clinical trial will encompass important endpoints such as postoperative pain and related symptoms using the MD Anderson Symptom Assessment Index (MDSAI), as well as cancer specific Functional Assessment of Cancer Therapy (FACT-Cx) and the general 12-Item Short-Form Health Survey (SF-12).

RATIONALE FOR LYMPHATIC MAPPING Published experience with the techniques for lymphatic mapping and sentinel lymph node detection in women with cervical cancer has been very limited. To date, no single study has enrolled more than 100 patients undergoing lymphatic mapping as part of their surgical treatment for cervical cancer. In fact, the majority of studies report on less than 50 patients. In addition, this procedure has not yet been shown to be viable in a multi-institutional setting. The limitations of previously published reports are important as these techniques are associated with a significantly high learning curve with early procedures less successful than later ones. This study will provide us the opportunity to enroll large numbers of patients for validation of intraoperative lymphatic mapping in women with cervical cancer in an international, multi-institutional setting.

Laparoscopic Approach to Cervical Cancer

A Phase III Randomized Clinical Trial of Laparoscopic or Robotic Radical Hysterectomy Versus Abdominal Radical Hysterectomy in Patients With Early Stage Cervical Cancer

date and localization of 1st recurrence as confirmed histologically - Compare patterns between groups

M.D. Anderson Cancer Center

Queensland Centre for Gynaecological Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 2 Study of EC145 Alone Versus EC145+Docetaxel Versus Docetaxel Alone in Participants With FR(++) 2nd Line Non Small Cell Lung Cancer	NCT01577654	Non Small Cell ...	EC145 EC145 + Docetax... Docetaxel EC20	18 Years -	Endocyte
Phase 2 Study of EC145 Alone Versus EC145+Docetaxel Versus Docetaxel Alone in Participants With FR(++) 2nd Line Non Small Cell Lung Cancer	NCT01577654	Non Small Cell ...	EC145 EC145 + Docetax... Docetaxel EC20	18 Years -	Endocyte
Laparoscopic Approach to Cervical Cancer	NCT00614211	Cervical Cancer	Total Abdominal... Total Laparosco...	18 Years -	Queensland Centre for Gynaecological Cancer

Spots Global Cancer Trial Database for adenosquamous