Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Recurrence

Carcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Dose escalation cohort will include all patients with solid tumors. Eribulin mesylate 1.1 mg/ m2 on days 1 and 8 followed by cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle.The highest dose level at which no more than one of six subjects experience DLT defines the MTD

Dose escalation cohort will include all patients with solid tumors. Eribulin mesylate 1.4 mg/ m2 on days 1 and 8 followed by cyclophosphamide 600 mg/ m2 on day 1 of a 21-day cycle.The highest dose level at which no more than one of six subjects experience DLT defines the MTD

Dose-expansion cohort will enroll patients with advanced breast cancer only after Phase Ib enrollment has been concluded. The MTD of Eribulin mesylate will be administered on days 1 and 8 followed by cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle.

Given intravenously (IV)

Phase II: Eribulin mesylate (mg/m2) + Cyclophosphamide (mg/ m2) for advanced breast cancer participants only

Eribulin

Hope S Rugo, MD

The purpose of this study is to test the safety of eribulin (Halaven™) and cyclophosphamide (Cytoxan®) given together at different doses. This study will look at what effects, good and/or bad, that these drugs have on solid tumors. Eribulin is a drug that has been approved by the FDA for breast cancer that has spread to other parts of the body. Cyclophosphamide has been approved for different types of cancers (including breast cancer). However, the combination of eribulin and cyclophosphamide is considered experimental; that means this combination has not been approved by the FDA.

The funding for this study is provided by Eisai Inc., the maker of eribulin.

This is a phase Ib/II trial designed to determine the maximum tolerated dose (MTD) and does limiting toxicities (DLTs) of the combination of eribulin and cyclophosphamide in solid tumors and make preliminary estimates regarding efficacy of this treatment in patients with advanced breast cancer.

The study includes a standard dose-confirmation schema (phase Ib portion) enrolling 3 to 6 patients/subjects, with any solid tumors, per cohort (3+3 design) with a total of 18 patients. The dose-expansion (phase II portion) will enroll 40 patients with advanced breast cancer to detect an effect size of 15% with a power of 80% with endpoints of safety, efficacy, and clinical benefit rate. A maximum of 58 patients will be enrolled on the phase Ib and II portions of this trial combined and will be treated until disease progression or toxicity mandate treatment change.

Eribulin is a non-taxane microtubule inhibitor that is FDA approved as monotherapy for the treatment of taxane and anthracycline resistant metastatic breast cancer. The combination of docetaxel and cyclophosphamide is a well-accepted adjuvant chemotherapy regimen that has become an increasingly common therapeutic choice for intermediate risk early stage breast cancer. Eribulin has a favorable toxicity profile compared to docetaxel with the most common adverse reactions (incidence ≤25%) including neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, and constipation. Eribulin appears to have activity in taxane resistant disease, making it an attractive partner with cyclophosphamide.

Neuropathy can be a devastating complication from adjuvant chemotherapy and in the metastatic setting, may limit effective therapy and reduce quality of life. Understanding the host factors that predict risk for neuropathy is critical, as these patients may in particular benefit from the lower risk of neuropathy associated with eribulin therapy. In conjunction with this trial, we have included correlative studies to study the proposed pharmacogenomic factors associated with risk of neuropathy. In this way we will potentially be able to identify patients who could preferentially be treated with less neurotoxic microtubule inhibitors.

Eribulin in Combination With Cyclophosphamide in Patients With Solid Tumor Malignancies

A Phase Ib/II Study of Eribulin in Combination With Cyclophosphamide in Patients With Solid Tumor Malignancies

Standard dose-confirmation design of 3 to 6 participants per cohort (3+3 design) was used to determine the MTD of eribulin in combination with cyclophosphamide for participants with any solid tumor. The highest dose level or MTD is reached when no more than one of six participants experience a Dose Limiting Toxicity (DLTs). A DLT is defined as any treatment-related toxicity in first 28 days of therapy with a grade 3 or 4 non-hematologic toxicity, a grade 4 neutropenia or thrombocytopenia lasting \>7 days or febrile neutropenia, or any clinically significant toxicity grade 2 or higher that requires more than 14 days to resolve. The highest dose level at which no more than one of six participants experience DLT defines the MTD.

The clinical benefit rate is defined as the proportion of participants with confirmed complete response (CR), partial response (PR) and stable disease (SD) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Responses are determined by changes in the largest diameter of the tumor lesions and the shortest diameter in the case of malignant lymph nodes. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter, PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters, and SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Only participants with measurable disease present at baseline, received at least 1 cycle of therapy, and had disease re-evaluated will be considered evaluable.

Safety of combination of eribulin and cyclophosphamide in participants was assessed by monitoring the frequency of treatment-related toxicities according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 with an attribute of possibly, probably, or definitely related to treatment. Number of participants by toxicity will be reported.

For the purposes of Phase Ib dose escalation, DLTs will be defined as any treatment-related toxicity occurring within the first 21 days of combination therapy as grade 3 or 4 clinically evident non-hematologic toxicity; grade 4 neutropenia or thrombocytopenia lasting \> 7 days or febrile neutropenia; or any clinically significant toxicity grade 2 or higher that requires more than 14 days to resolve.

The ORR is defined as the proportion of participants displaying a CR or PR per RECIST criteria recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The participant's best response will depend on the achievement of both measurement and confirmation criteria with CR defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter and PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Time to progression will be evaluated as time from first treatment to tumor progression in weeks. Disease progression will be measured using Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (uni-dimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST 1.1 criteria.

Eisai Inc.

University of California, San Francisco

Dose escalation cohort will include all patients with solid tumors. Eribulin mesylate 1.1 mg/ m2 on days 1 and 8 followed by cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle.The highest dose level at which no more than one of six subjects experience DLT defines the MTD

Eribulin: Given intravenously (IV) Cyclophosphamide: Given IV

Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)

Dose escalation cohort will include all patients with solid tumors. Eribulin mesylate 1.4 mg/ m2 on days 1 and 8 followed by cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle.The highest dose level at which no more than one of six subjects experience DLT defines the MTD

Eribulin: Given intravenously (IV) Cyclophosphamide: Given IV

Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)

Dose-expansion cohort will enroll patients with advanced breast cancer only after Phase Ib enrollment has been concluded. The MTD of Eribulin mesylate will be administered on days 1 and 8 followed by cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle.

Eribulin: Given intravenously (IV) Cyclophosphamide: Given IV

Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)

Dose escalation cohort will include all patients with solid tumors. Eribulin mesylate 1.1 mg/m2 on days 1 and 8 followed by cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle. The highest dose level at which no more than one of six subjects experience DLT defines the MTD

Eribulin: Given intravenously (IV) Cyclophosphamide: Given IV

Dose escalation cohort will include all patients with solid tumors. Eribulin mesylate 1.4 mg/m2 on days 1 and 8 followed by cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle. The highest dose level at which no more than one of six subjects experience DLT defines the MTD

Eribulin: Given intravenously (IV) Cyclophosphamide: Given IV

Total

30-39 years old

40-49 years old

50-59 years old

60-69 years old

70-79 years old

80-89 years old

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Hope Rugo, MD

Dose escalation cohort will include all patients with solid tumors. Eribulin mesylate 1.1 mg/ m2 on days 1 and 8 followed by cyclophosphamide 600 mg/ m2 on day 1 of a 21-day cycle.The highest dose level at which no more than one of six subjects experience DLT defines the MTD

Eribulin: Given intravenously (IV) Cyclophosphamide: Given IV

Phase 1b: Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)

Maximum Tolerated Dose (MTD) in Participants With Any Solid Tumor (Phase Ib)

Clinical Benefit Rate for Patients With Advanced Breast Cancer (ABC) (Phase II)

Nausea

Constipation

Fatigue

Peripheral sensory neuropathy

Anorexia

White blood cell decreased

Mucositis oral

Platelet count decreased

Alopecia

Arthralgia

Hemoglobin increased

Headache

Chills

Alanine aminotransferase increased

Rash maculo-papular

Epistaxis

Hypomagnesemia

Edema limbs

Vomiting

Abdominal pain

Anemia

Investigations - Other

Dysgeusia

Alkaline phosphatase increased

Hoarseness

Fever

Neutrophil count decreased

Diarrhea

Hypokalemia

Weight loss

Gastrointestinal disorders - Other

Nasal congestion

Cough

Upper respiratory infection

Sinusitis

Febrile neutropenia

Bone pain

Blurred vision

Peripheral motor neuropathy

Dyspnea

Gastroesophageal reflux disease

Lymphocyte count decreased

Dizziness

Hypoalbuminemia

Hot flashes

Aspartate aminotransferase increased

Memory impairment

Postnasal Drip

Insomnia

Pain

Non-cardiac chest pain

Hypoxia

Portal vein thrombosis

Sepsis

Confusion

Hypophosphatemia

Pain in extremity

Hypercalcemia

Dysphagia

Hyponatremia

Myalgia

Number of Participants With Treatment-related Toxicities

Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid

Number of Participants With Dose Limiting Toxicity (DLT) for Participants With Any Solid Tumor (Phase 1b)

Overall Response Rate (ORR) for Participants With Advanced Breast Cancer (Phase II)

Time to Progression for Participants With Advanced Breast Cancer (Phase II)

Dose escalation cohort will include all patients with solid tumors. Eribulin mesylate 1.4 mg/ m2 on days 1 and 8 followed by cyclophosphamide 600 mg/ m2 on day 1 of a 21-day cycle.The highest dose level at which no more than one of six subjects experience DLT defines the MTD

Eribulin: Given intravenously (IV) Cyclophosphamide: Given IV

Overall Study

Disease Attributes

Ifosfamide

Isophosphamide mustard

Mechlorethamine

Experimental study drug monotherapy arm (A)

Oral activator ligand with adenoviral vector injection of cancer lesions

Ad-RTS-hIL-12 and Veledimex

Small molecule chemotherapy, IV administration

Palifosfamide

Francois Lebel, MD

Phase II, randomized, safety and efficacy study in recurrent/metastatic breast cancer with accessible lesions.

Primary End point is rate of Progression Free Survival (PFS) at the 16 week treatment time point. Hypothesis: Adenoviral vector (Ad-RTS-hIL-12) alone and in combination with chemotherapy (palifosfamide) is safe and efficacious.

Multicenter, open-label, randomized study evaluating the safety and efficacy of INXN-1001 (veledimex) and INXN-2001 (Ad-RTS-hIL-12) alone and in combination with palifosfamide.

Part 1 is the safety run-in where a safety assessment will be made after 1 cycle of therapy.

Part 2, eligible subjects will be randomly assigned to active treatment Arms A or C.

Once the monotherapy (Arm A) is determined to be safe and tolerable, Part 1 combination therapy (Arm C) will begin.

Subjects should receive six cycles of study treatment, in the absence of meeting withdrawal criteria.

Adenoviral Vector Monotherapy or Combination With Chemotherapy in Subjects With Recurrent/Metastatic Breast Cancer.

A Phase II Randomized, Open Label Study of Ad-RTS-hIL-12 Monotherapy or Combination With Palifosfamide in Subjects With Recurrent/Metastatic Breast Cancer and Accessible Lesions

Proportion of subjects achieving a confirmed PR or CR according to modified RECIST v1.1

Alaunos Therapeutics

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

NK105

Call +81-3-6731-5200 Mon - Fri 9 AM - 5 PM (Japan Time)

To verify the non-inferiority of NK105, a paclitaxel-incorporating micellar nanoparticle, to paclitaxel in terms of the progression-free survival in patients with metastatic or recurrent breast cancer.

This study is a randomized, open-label, multi-national phase III study.

A Phase III Study of NK105 in Patients With Breast Cancer

A Multi-national Phase III Clinical Study Comparing NK105 Versus Paclitaxel in Patients With Metastatic or Recurrent Breast Cancer

PFS is defined as the period from the day of randomization until the first observation of lesion progression or death from any cause. Disease progression is defined as PD according to RECIST Ver. 1.1.

Assessment period was from the day of randomisation until the first observation of lesion progression or death

OS is defined as the period from the day of randomization until the day of death from any cause.

Assessment period was from the day of randomisation until the first observation of lesion progression or death

ORR is the proportion of patients who are assessed as complete response or partial response as the best overall response among evaluable patients, according to RECIST Ver.1.1.

Assessment period was from the day of randomisation until the first observation of lesion progression or death

Nippon Kayaku Co., Ltd.

received NK105 (65 mg/m\^2) on days 1, 8 and 15 of a 28-day cycle

received Paclitaxel (80 mg/m\^2) on days 1, 8 and 15 of a 28-day cycle

Age, Continuous

Japan

South Korea

Taiwan

All randomized patients who received study drug at least once

Pharmaceuticals Group

Based on the results of previous studies, the expected median PFS was 5.5 months for PTX and 6.35 months for NK105. Assuming a randomization period of 18 months, a follow-up period of 12 months, a one-sided significance level of 2.5%, a power of 85% and the non-inferiority margin of 1.215, the number of patients was estimated to 172 pts per group, a total of 344 patients. Considering an expected withdrawal/dropout rate of approximately 20%, the target sample size was set at 414.

All randomized patients who received study drug at least once and who had no major violations of the eligiblity criteria

Progression Free Survival

History of chemotherapy for metastatic or recurrent breast cancer (yes/no), History of treatment using a taxane anticancer drug (yes/no), ER status \[ER (+) or ER (-)\], and Disease free interval (\<12 months or ≥12 months) were covariates for adjustment.

Overall Survival

Overall Response Rate

Rare Diseases

Chronic Graft Versus Host Disease

Standard treatment of breast cancer with intervention : samples collection

blood sampling

Catherine Gaudin

Anne Laure Martin

Fabrice ANDRE

Laetitia Shanna RAJPAR

Patrick SOULIE

Severine GUIU

Laurence VANLEMMENS

Marion FOURNIER

Anne LESUR

Olivier TREDAN

Paul henri COTTU

Christelle LEVY

Mario CAMPONE

Carole TARPIN

Florence LEREBOURS

Hervé CURE

Marie Ange MOURET REYNIER

Olivier RIGAL

Jean Marc FERRERO

Thierry PETIT

Pierre KERBRAT

Antoine ARNAUD

Fabrice André

The aims of the cohort will be to quantify impact of cancer treatments toxicities , and to generate predictors of chronic toxicity in patients with non-metastatic cancer. Study of the original cohort will be focused on localized breast cancer patients, other localisation in non-metastatic setting will be explored furtherwise, fist of all in lung cancer.

The project will include four specific aims :

1. To develop a database of chronic treatment related toxicity in a cohort of 14750 women with stage I-III breast cancer (= non metastatic), whatever these treatments are (surgery; radiation therapy; chemotherapy ...)
2. To describe incidence, clinical presentation, and outcome of chronic toxicities.
3. To describe the psychological, the social and the economic impacts of chronic toxicities.
4. To generate predictors for chronic toxicities in order to prevent them, based upon biological criteria.

The expected impact of these toxicities, when identified, will be to improve quality of life and to decrease health cost, by the early identification of patients at high risk of toxicity. Such early identification could lead to prevent toxic effect by: a. developing prevention strategies, b. substituting toxic treatment by a non (less) toxic one.

Also, such cohort will offer a quantification of the impact of treatment toxicity, that could be further used to quantify medical usefulness of strategies that aim at decreasing treatment toxicities (implementation of predictive biomarker for resistance, cytotoxic-free regimen etc...)

SPECIFIC AIM I: TO DEVELOP A TOXICITY DATABASE ON A COHORT OF 20,000 WOMEN WITH STAGE I-III (NON METASTATIC) BREAST CANCER

Selection criteria The cohort will include female patients with non-metastatic breast cancer (stage I-III) without any selection based on their characteristics (except stage) or treatment. They may be included in other concomitant clinical studies.

Patients will have to sign informed consent and will have to benefit from social security.

The lack of selection criteria is related to the fact that the cohort aims at investigating toxicity in the whole population of breast cancer from a public health perspective.

Sample size The cohort plans to include 14750 women in 13 years. A cohort of 14750 patients will allow to detect a two fold increased in the risk of a specific toxicity in a homogenous subgroup.

As illustration, the study present a 90% power to detect whether a variable (age as example) observed in 50% of patients is associated with an increased risk of toxicity (heart toxicity) in a specific subgroup (Her2+++).

Development of the cohort The14750 patients will be recruited in 26 cancer centers, maximum in France. These patients will be followed for at least 5 years in the context of the cohort. After 5 years, additional specific data will then be captured each year.

Patients will be included at the time of diagnosis, before any cancer specific treatment. After having signed informed consent, the patient will fill a first questionnaire for demographics (adapted from French DREES reference study) and living conditions, and a set of validated questionnaires related to QoL and special psychological dimensions. In addition, blood samples will be collected at baseline.

The toxicities (events) will start to be collected 3 months after the end of "acute" treatment (surgery/adjuvant/chemotherapy/radiation therapy). Toxicity data will also be collected at the time of the last chemotherapy. Toxicities will be collected each 6 months, alternatively by a dedicated nurse and by the patient herself. Three sets of toxicities will be collected.

* First, predefined and previously described toxicities will be collected on dedicated items in the case report form.
* Second, unknown toxicities will be captured by the use of a patient's notebook where each patient will collect events and doctor' visits (general practitioner or organ specialist). This will allow capturing events that have not previously been associated with cancer treatment toxicities.
* Finally, objective measurements by paraclinic exams will be done. This includes yearly blood tests and a heart ultrasonography at 1 and 5 years.

In addition to the data collection, a baseline blood sample for genetic analyses will be done, and serum samples will be collected at baseline and yearly during 5 years (serum).

Outcome data will also be collected and will include metastatic relapse (+ site), locoregional relapse (+ site) and death.

SPECIFIC AIM II: TO DESCRIBE INCIDENCE, CLINICAL PRESENTATION, BIOLOGICAL CHARACTERISTICS AND OUTCOME OF CHRONIC TOXIC EVENTS

This specific aim will follow three goals :

* First, the investigators will describe the incidence of predefined chronic toxicities according to the treatment received.
* Second, the investigators will aim at identifying new treatment-related toxicities. This information will be captured through a dedicated notebook where each patient will report all health and social related events.
* Finally, the investigators will also assess the outcome of each adverse event, and try to develop some hypotheses to be addressed in further clinical trials.

SPECIFIC AIM III: TO DESCRIBE THE PSYCHOLOGICAL AND THE SOCIAL IMPACTS OF TOXIC EVENTS This specific aim will be split in two parts: a. to describe the psychological and the social impact to the patient, b. to describe the impact at the population level.

To describe psychological and social impact for the patient

Using robust well validated methods, subjective and objective dimensions of wellbeing will be investigated, that is: a. Quality of life b. Living conditions c. Psychosocial issues.

Quality of life Global perception of quality of life will be assessed through different survey

Social impact Living conditions will be assessed through a questionnaire derived from the French DRESS reference study on living conditions. The initial questionnaire was designed by DRESS to investigate the social, economical, professional condition two years after the diagnosis of cancer: back or abandonment of the initial professional/social activity, conversion, income trends, etc.

Psychological impact This part will focus on psychological functioning, including psychological impact of chronic toxicities and psychological impact of cancer itself. Psychological impact is mainly expected on emotional issues, cognitive disorders, body image and sexual disorders.

To describe the impact on the society This sub-aim will mainly focus on medico-economics and will assess the global impact of treatment toxicity on health economy. The quantification of costs related to toxicities is a major challenge since it could allow to identify avoidable major source of expenses and could allow better tailoring treatment accordingly. Specific partnerships are being developed with the French social security and other public/private partners in order to accurately quantify toxicity-related cost.

SPECIFIC AIM IV TO DEVELOP PREDICTORS FOR CHRONIC TOXICITIES In the present specific aim, the goal will be to develop molecular/biologic predictors for toxic events. In as many cases as possible, the investigators will split the cohort into a discovery set and a test set, or will identify a cross-validating series before doing analyses.

Ultimately, the goal is to develop multiparametric scores to predict the occurrence of toxicity.

Regarding molecular predictors, it is planned that 20 ml blood will be collected yearly. One sample at baseline will be dedicated to single nucleotide polymorphism (SNP) arrays and validation of candidate genetic variants.

A number of tests are already planned. First, we will investigate conventional biological parameters including endocrine tests (cortisolemia, TSH, estradiol levels, mullerian hormone...), metabolic test (including lipidemia), hematologic tests, liver function, immune function (assessed by lymphocyte counts). Second, more recent and under investigation tests will be added including troponin (heart failure), mullerian hormone, bone resorption markers (bone loss), RANK / RANKL, osteoprotegerin (bone loss).

Finally, it is planned to use the baseline sample for the discovery of genetic tests and to use the serum for the discovery of biochemical predictors.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Eribulin in Combination With Cyclophosphamide in Patients With Solid Tumor Malignancies	NCT01554371	Malignant Solid... Breast Cancer N... Neuropathy	Eribulin Cyclophosphamid...	18 Years - 80 Years	University of California, San Francisco
Adenoviral Vector Monotherapy or Combination With Chemotherapy in Subjects With Recurrent/Metastatic Breast Cancer.	NCT01703754	Breast Cancer N...	Ad-RTS-hIL-12 a... Palifosfamide	18 Years -	Alaunos Therapeutics
A Phase III Study of NK105 in Patients With Breast Cancer	NCT01644890	Breast Cancer N...	NK105 Paclitaxel	20 Years - 74 Years	Nippon Kayaku Co., Ltd.
Chronic Toxicities Related to Treatment in Patients With Localized Cancer	NCT01993498	Breast Cancer N...	blood sampling	18 Years -	UNICANCER
A Phase III Study of NK105 in Patients With Breast Cancer	NCT01644890	Breast Cancer N...	NK105 Paclitaxel	20 Years - 74 Years	Nippon Kayaku Co., Ltd.

Spots Global Cancer Trial Database for breast cancer nos metastatic recurrent