Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Carcinoma, Ductal, Breast

Inflammatory Breast Neoplasms

Carcinoma

Carcinoma, Ductal

Breast Diseases

Skin Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Inflammatory Breast Cancer

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Paclitaxel

Cyclophosphamide

Albumin-Bound Paclitaxel

Epirubicin

Pertuzumab

Tubulin Modulators

Antimitotic Agents

nab-Paclitaxel (125 mg/m² weekly, infusion) is applicated for 12 weeks, followed by epirubicin and cyclophosphamide, applicated 4 cycles 3-weekly . In case of HER2-positive tumor patients receive tarstuzumab and pertuzumab 3-weekly during all cycles.

Paclitaxel (80 mg/m² weekly, infusion) is applicated for 12 weeks, followed by epirubicin and cyclophosphamide, applicated 4 cycles 3-weekly . In case of HER2-positive tumor patients receive tarstuzumab and pertuzumab 3-weekly during all cycles.

nab-Paclitaxel 125 mg/m² weekly for 12 weeks

nab-Paclitaxel

Michael Untch, Prof MD

Current guidelines as those from the AGO-Breast commission recommend for neoadjuvant breast cancer patients either a sequence of 4 cycles EC followed by 4 cycles of a taxane or 6 cycles of TAC based on previous large scale studies.

Treatment of patients with HER2-positive disease should include also simultaneous application of trastuzumab.

Solvent-based taxanes (paclitaxel, docetaxel) cause severe toxicities not only by the active agents itself but also by the solvents like cremophor. Nab-paclitaxel (Abraxane®) is a solvent-free formulation of paclitaxel encapsulated in albumin. It does not require premedication with corticosteroids or antihistamines to prevent the risk of solvent-mediated hypersensitivity reactions. This new formulation improves safety profile, allows higher dosing with shorter infusion duration, and produces higher tumor drug concentration.

As neoadjuvant treatment does not only allow to compare competing treatment approaches with a very high quality (homogenous treatment population, precise assessment of response by histological assessment), but also to identify predictive markers, this trial will compare weekly nab-paclitaxel with solvent-based paclitaxel at their currently optimal doses.

In case of HER2-positive tumor status patients receive Pertuzumab and Trastuzumab additionally.

Primary Objectives:

To compare the pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment of nab-paclitaxel with solvent-based paclitaxel as part of neoadjuvant treatment of operable or locally advanced primary breast cancer

Secondary Objectives:

* To assess the pCR rates per arm separately for the stratified subpopulations.
* To determine the rates of ypT0/is ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0; and regression grades.
* To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in both arms.
* To assess clinical response rate after taxane in both groups
* To determine the breast conservation rate after each treatment.
* To assess the toxicity and compliance.
* To assess the time of onset of grade 3 neuropathy
* To assess the time of resolution of grade 3/4 neuropathy to at least grade 1
* To determine loco-regional invasive recurrence free survival (LRRFS), distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), and overall survival (OS) in both arms and according to stratified subpopulations.
* To assess regional recurrence free survival (RRFS) in patients with initial node-positive axilla converted to negative at surgery and treated with sentinel node biopsy alone.
* To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery.
* To examine and compare pre-specified molecular markers such as SPARC, gp60, calveoline 1 and other markers potentially differentially predicting efficacy of nab-paclitaxel and solvent-based paclitaxel on core biopsies before, during and after chemotherapy.

Objectives of Substudies:

* To assess, characterize, and correlate circulating tumor cells and proteins with the effect of treatment (CTC Substudy).
* To correlate Single Nucleotide Polymorphisms (SNPs) of genes with the associated toxicity and histologically assessed treatment effect (Pharmacogenetic substudy)
* To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, LH , Anti-Müller Hormone, ultrasound-follicle count in patients aged \< 45 years.

Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)

A Randomized Phase III Trial Comparing Nanoparticle-based Paclitaxel With Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Patients With Early Breast Cancer (GeparSepto)

No microscopic evidence of residual invasive or non-invasive viable tumor cells in all resected specimens of the breast and axilla.

Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries.

The primary endpoint will be summarized as pathological complete remission rate for each treatment group.

Response (by physical examination, imaging response, breast conservation) will also be summarized as rates in each treatment group.

To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in both arms.

Descriptive statistics for the 4 treatments (each taxane +/- anti-HER2-treatment) will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.

To assess clinical response rate after taxane in both groups.

To determine the breast conservation rate after each treatment.

To assess the time of onset of grade 3 neuropathy.

To assess the time of resolution of grade 3/4 neuropathy to at least grade 1.

To assess regional recurrence free survival (RRFS) in patients with initial node-positive axilla converted to negative at surgery and treated with sentinel node biopsy alone.

To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery.

To examine and compare pre-specified molecular markers such as SPARC, gp60, calveoline 1 and other markers potentially differentially predicting efficacy of nab-paclitaxel and solvent-based paclitaxel on core biopsies before, during and after chemotherapy.

The aim is to identify potential predictive short and long term parameters.

To assess, characterize, and correlate circulating tumor cells and proteins with the effect of treatment.

To correlate Single Nucleotide Polymorphisms (SNPs) of genes with the associated toxicity and histologically assessed treatment effect.

To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, LH , Anti-Müller Hormone, ultrasound-follicle count in patients aged \<45 years.

LRRFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

DDFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

IDFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

OS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

If it can be shown at an interim analysis that the positive predictive value for a pCR of a negative (\>=3) core biopsies before surgery in patients with complete clinical response is \>90%, these patients might opt for having no further breast surgery.

Celgene Corporation

Roche Pharma AG

German Breast Group

Amino Acids

Trastuzumab

Carboplatin

Bevacizumab

Lapatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Carboplatin AUC 2 min/mL weekly, infusion will be used as Add-on to the background therapy (same as comparator arm)

background treatment with NLPD (Myocet), Paclitaxel, Herceptin (Trastuzumab fpr Her2 pos), Tyverb (Lapatinib for Her2 pos), Avastin (Bevacizumab for triple negative) agents are used according to marketed formulation via normal procedures at each site and applied according to recommendations of the manufacturers.

Carboplatin, AUC, 2 min/mL weekly, infusion

background treatment according to standards fpr triple negative and Her2pos breast cancer patients Paclitaxel: 80 mg/m² i.v. given weekly on day 1 q day 8 for 18 weeks. NPLD (Myocet®): 20 mg/m² weekly on day 1 q day 8 for 18 weeks Trastuzumab (only for HER2-positive patients): Loading dose: 8 mg/kg, Maintenance dose: 6 mg/kg, day 1 q day 22 for 6 cycles. Post-surgery: up to a total duration of 1 year according to current AGO guidelines Lapatinib 750 mg/day p.o. continuously for 18 weeks; in case of good tolerability (no CTC grade II toxicity except alopecia and nausea/vomiting) during the first cycle the dose may be escalated to 1000 mg.

Bevacizumab: 15 mg/kg i.v., day 1 q day 22 for 6 cycles (only in TNBC patients).

background treatment

Gunter von Minckwitz, MD, Prof

Study participants with primary breast cancer will receive a standard chemotherapy with an anthracycline and a taxane as well as trastuzumab in case of HER2-positive tumors at doses and duration in concordance to current treatment guidelines. Patients will be receive and benefit in addition currently not in the neoadjuvant setting registered medication as lapatinib or bevacizumab of which significant increases of cure (pCR) rates have been reported in previous phase III studies. Patients randomized to carboplatin will receive in addition to the described backbone therapies a potentially active agent which suggested synergy of efficacy with chemotherapies as well as targeted agents. Patients might have the risk of an increase in toxicities due to the added agents and will have additional burden due to investigations required for study participation. However, due to the severity of the underlying disease and the high risk of relapse and death due to the stage of disease, this increase in toxicity and burden appears less relevant compared to the potential higher efficacy and finally cure rate by the incorporated treatments.

Anthracycline/taxane based combination chemotherapy of at least 18 weeks represents the standard of care in the neoadjuvant setting. In HER2-positive disease trastuzumab is given simultaneously to chemotherapy. Recent data from the Neo-Altto and Neosphere trials suggest that a dual blockage of the HER2 receptor with e.g. trastuzumab and lapatinib reach significantly higher pCR rates than trastuzumab alone and should therefore represent the treatment back-bone of new neoadjuvant trials. A preplanned subgroup analysis of the GeparQuinto study demonstrated that in TNBC the addition of bevacizumab resulted in a significant increase of pCR rates (HR 1.4).

Having a better cardiac tolerability profile compared to conventional anthracyclines, the non-pegylated liposomal encapsulated doxorubicin (NPLD) Myocet® might provide the possibility to combine taxane, anthracycline, platinum salt as well with targeted agents as double HER2 blockage or bevacizumab.

Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer

A Randomized Phase II Trial Investigating the Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer

Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries. Surgery takes place shortly after the 18 weeks (six 3-week cycles) chemotherapy treatment. No microscopic evidence of residual viable tumor cells in all resected specimens of the breast and axilla meets the primary endpoint.

To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests. (sonography, mammography, or MRI) after treatment in both arms.

LRRFS, RRFS, LRFS, DDFS, IDFS and OS are defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

Tolerability and Safety: Descriptive statistics for the 4 treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped

• To assess the pCR rates per arm separately in patients with triple-negative tumors and HER2-positive tumors.

To determine the breast and axilla conservation rate after each treatment.

To assess the pCR rate in patients with a clinical complete response and a negative core biopsy before surgery.

To examine and compare pre-specified molecular markers such as BRCA1-mRNA, P53, ALDH1, p4E-BP1, IL-8 metagene, B-Cell metagene as well as exploratory analyses and lymphocyte infiltration on core biopsies before and surgical tissue after end of chemotherapy. The aim is to identify potential predictive short and long term parameters.

To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, Anti-Müller Hormone, ultrasound-follicle count in patients aged \<45 years.

Teva Pharmaceuticals USA

GlaxoSmithKline

Symptoms and General Pathology

Triple Negative Breast Neoplasms

Neoplasm Metastasis

Cancer Pain

Pain

Neoplastic Processes

Self-administered hypnosis will be practiced daily, at home for 6 weeks. Hypnosis sessions are expected to last \~20 minutes. Practices using the recordings will be documented on the Hypnosis Practice Log.

Self-administered white noise hypnosis will be practiced daily using a white noise recording. Participants will practice hypnosis at home after completing the virtual consent/baseline visit and the virtual education visit.

Participants will choose from one of three 20-minute prerecorded hypnosis audio files. Practices using the recordings will be documented on the hypnosis practice log.

Self-Administered Hypnosis

Participants will be listening to the same 20-minute white noise audio recording for 6 weeks and will be encouraged to practice daily. Practices using the recordings will be documented on the hypnosis practice log.

Self-Administered White Noise Hypnosis

Noel M Arring, DNP, PhD, RN

The purpose of this study is to compare two hypnotic interventions for Black women with advanced cancer pain in preparation for a well-powered phase III study. The investigators plan to enroll 30 adult Black women with advanced cancer pain in a 2-arm pilot randomized controlled trial (RCT).

The primary aim will be to evaluate the feasibility of conducting the 2-arm clinical trial. It is hypothesized that at least 75% of participants in both study arms will complete study requirements. The secondary aims will be to evaluate the participant's experience with the intervention and to determine the effect size of the intervention on pain severity.

Envision is a randomized, 2-arm, mixed-methods pilot study to evaluate the feasibility of translating a promising in-person hypnosis intervention for advanced cancer pain into a culturally appropriate, remotely delivered hypnosis intervention for pain in Black women with advanced cancer. The study is 6 weeks long and does not require any in-person visits. If a breast cancer survivor is determined eligible, they will be educated on the purpose, requirements, and procedures. If interested, participants will be emailed the consent form and will schedule a virtual consent/baseline visit. After consent is obtained, the participant will be randomly assigned to one of two types of hypnotic relaxation to be used alongside current pain treatment using 1:1 randomization and given a study number. The participant will complete online surveys at the virtual baseline visit. An MP3 player with hypnotic relaxation audio files will be sent to the participant's address and a virtual education visit will be scheduled. At this second virtual visit, participants will receive education about their study arm and a start date will be agreed upon for week 1. Beginning week 1 and continuing through week 6, participants will listen to their assigned hypnotic relaxation audio files daily and be asked to complete a weekly practice log. Participants will also continue to meet with study staff virtually for weekly check-ins. At these weekly meetings, progress and adverse events will be assessed and relevant online surveys will be completed.

This is a two-arm, randomized clinical trial.

Hypnosis for Pain in Black Women With Advanced Breast Cancer: A Feasibility Study

This is a small pilot study and as such, data will be thoroughly interrogated. However, if an investigator feels there are unanswered questions or wishes to add to a larger dataset, we would entertain all data-sharing requests for deidentified data as appropriate.

The number of participants who consented divided by the number eligible

The number of participants who complete the 6 weeks of the study divided by the number who consented.

Determine factors affecting participant experience through open-ended interview questions.

Change in Brief Pain Inventory-Short Form scores. The Brief Pain Inventory-Short Form contains two subscales, pain severity and pain interference. Both scales include individual items that are scored on a scale of 0-10. The pain severity scale includes 4 items, with a possible range of 0-40. The pain interference scale includes 7 items, with a possible range 0-70. Higher scores indicate greater pain severity and greater pain interference.

Baylor University

The University of Tennessee, Knoxville

Associate Professor

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants received Bemcentinib (BGB324) capsules orally once daily as a loading dose of 400 milligram (mg) on Days 1, 2, and 3. A dose of 200 mg pembrolizumab was given by intravenous infusion over 30 minutes every 3 weeks in all participants. Dosing of both drugs commenced on Day 1. On days when both BGB324 and pembrolizumab were given, pembrolizumab was given first and participants were observed for 1 hour after the end of infusion before BGB324 was administered. From Day 4 onward, participants received a daily maintenance dose of 200 mg along with Pembrolizumab 200 mg intravenous (IV) infusion over 30 minutes every 3 weeks until disease progression, until an unacceptable toxicity occurred that required treatment withdrawal or withdrawal of consent or until 106 weeks had passed.

Bemcentinib is a selective Axl kinase inhibitor; pembrolizumab is a programmed death receptor-1 (PD-1) inhibitor.

Bemcentinib; pembrolizumab

This is an open label, single arm, multi-centre phase II study to assess the anti-tumour activity and safety of bemcentinib (BGB324) in combination with pembrolizumab in participants with previously treated, locally advanced and unresectable, or metastatic TNBC or TN-IBC. The primary objective is objective response rate.

Extension to Simon's 2-stage design allowing termination at the end of Stage 1 for either futility or efficacy.

Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With TNBC

A Phase II, Multi Centre Study of BGB324 in Combination With Pembrolizumab in Patients With Previously Treated, Locally Advanced and Unresectable or Metastatic Triple Negative Breast Cancer (TNBC) or Triple Negative Inflammatory Breast Cancer (TN-IBC)

Individual participant data that underlie the results reported in the article, after deidentification \[text, tables, figures and appendices\].

ORR is defined as the percentage of evaluable participants who had at least one confirmed overall response of complete response (CR) or partial response (PR) according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. CR: Disappearance of all target lesions (TLs) since baseline, any pathological lymph nodes selected as TLs must have a reduction in short axis to less than (\<) 10 millimeter (mm). PR: At least a 30 percent decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.

DOR is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression (PD); the end of response should coincide with the date of progression or death from any cause. PD per modified RECIST 1.1 defined as: at least a 20 percent increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD). CR: Disappearance of all target lesions (TLs) since baseline, any pathological lymph nodes selected as TLs must have a reduction in short axis to \< 10 mm. PR: At least a 30 percent decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters. SD per modified RECIST 1.1 defined as: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

PFS was defined as the duration from start of treatment until the date of radiological disease progression (the date on which the confirmed progression was initially observed) or the date of death (regardless of cause of death), whichever was earlier.

OS was defined as the time from the first dose of study treatment until the date of death (from any cause and irrespective of any subsequent anti-cancer treatment given).

Merck Sharp & Dohme LLC

BerGenBio ASA

The safety set included all participants who were enrolled in the study and who received at least 1 dose of study product (bemcentinib and/or pembrolizumab).

Bemcentinib + Pembrolizumab

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

The Safety Set included all participants who were enrolled in the study and who received at least 1 dose of study product (BGB324 and/or pembrolizumab).

None of the participants achieved CR or PR. As there were no responses, the study was terminated. It was planned to terminate the trial in favor of the null hypothesis of futility when 5 or fewer responses were observed in 28 participants.

BerGenBio Clinical Team

The Evaluable analysis set (EAS) included all evaluable participants who had received at least 1 combination dose of pembrolizumab and bemcentinib and who had measurable disease at entry, as determined by the investigator site assessment.

Objective Response Rate (ORR)

Analysis performed on participants in EAS who had an objective response. DOR could not be calculated as none of the participants had an objective response.

Duration of Response (DOR)

The evaluable analysis set included all evaluable participants who had received at least 1 combination dose of pembrolizumab and bemcentinib and who had measurable disease at entry, as determined by the investigator site assessment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)	NCT01583426	Tubular Breast ... Mucinous Breast... Breast Cancer F... Invasive Ductal... Tubular Breast ... HER-2 Positive ... Inflammatory Br... Inflammatory Br...	nab-Paclitaxel Paclitaxel	18 Years -	German Breast Group
Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer	NCT01426880	Tubular Breast ... Mucinous Breast... Breast Cancer F... Invasive Ductal... Tubular Breast ... HER-2 Positive ... Inflammatory Br... Inflammatory Br...	Carboplatin background trea...	18 Years -	German Breast Group
Hypnosis for Pain in Black Women With Advanced Breast Cancer: A Feasibility Study	NCT06057636	Breast Cancer Inflammatory Br... Inflammatory Br... Triple Negative... Neoplasm Metast...	Self-Administer... Self-Administer...	18 Years - 99 Years	The University of Tennessee, Knoxville
Hypnosis for Pain in Black Women With Advanced Breast Cancer: A Feasibility Study	NCT06057636	Breast Cancer Inflammatory Br... Inflammatory Br... Triple Negative... Neoplasm Metast...	Self-Administer... Self-Administer...	18 Years - 99 Years	The University of Tennessee, Knoxville
Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With TNBC	NCT03184558	Triple Negative... Inflammatory Br...	Bemcentinib; pe...	18 Years -	BerGenBio ASA

Spots Global Cancer Trial Database for inflammatory breast cancer stage iv