Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Vaccines

Fulvestrant

Estrogens

Aromatase Inhibitors

Progesterone

THERATOPE® vaccine

The purpose of this study is to examine the immunological response rate to administration of the THERATOPE® vaccine in women with stable metastatic breast cancer who are being treated with aromatase inhibitors or Faslodex® and who do not require chemotherapy.

Post-menopausal women on aromatase inhibitors or Faslodex® alone and pre-menopausal women on aromatase inhibitors plus luteinising hormone-releasing hormone (LH/RH)-agonist may be eligible to be enrolled.

Patients must not have had radiotherapy or major surgery within four (4) weeks prior to entering the study.

Information about the safety and tolerability of administration of the THERATOPE® vaccine will also be gathered during the course of the study.

Safety and Immunological Response Rate Study of THERATOPE® Vaccine in Metastatic Breast Cancer Patients

Open-Label, Phase II Trial of Immunological Response Rate, Safety, and Tolerability of THERATOPE® Vaccine in Subjects With Metastatic Breast Cancer Undergoing Treatment With Aromatase Inhibitors or Faslodex®

Oncothyreon Canada Inc.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Paclitaxel

Albumin-Bound Paclitaxel

Bevacizumab

Carboplatin

Hormones

Exemestane

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Standard chemotherapy: paclitaxel 175 mg/m2 + carboplatin AUC 5, on day 1 every 21 days ± bevacizumab 15mg/kg, on day 1 every 21 days. Chemotherapy will be administered for 6 cycles; Bevacizumab will be administered as up to a maximum of 22 cycles. Patients unfit for standard treatment can receive a weekly schedule of treatment or monotherapy with carboplatin alone. Neoadjuvant chemotherapy is allowed in patients unfit for primary elective surgery.

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Exemestane: single oral tablet of 25 mg/day until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first.

Standard chemotherapy : paclitaxel 175 mg/m2 + carboplatin AUC 5, on day 1 every 21 days ± bevacizumab 15mg/kg, on day 1 every 21 days. Chemotherapy will be administered for 6 cycles; Bevacizumab will be administered as up to a maximum of 22 cycles. Patients unfit for standard treatment can receive a weekly schedule of treatment or monotherapy with carboplatin alone. Neoadjuvant chemotherapy is allowed in patients unfit for primary elective surgery.

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Placebo: single oral tablet until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first.

Exemestane in addition to standard therapy, in Experimental arm.

Placebo in addition to standard therapy, in Control arm.

Placebo oral tablet

Andrea DeCensi

In this Italian, multicenter, randomized, double-blind, placebo controlled, phase III study the efficacy of exemestane will be evaluated in addition to the standard front line treatment in patients with hormone-receptor-positive high grade serous or endometrioid Epithelian Ovarian Cancer (EOC). The patients enrolled in the EXPERT trial will receive exemestane or placebo in addition to standard treatment. Patients and investigators will be blinded to study treatment.

The hypothesis underlying the proposed clinical trial is that exemestane added to standard first line therapy will significantly prolong median progression free survival (PFS).

Estrogen and Progesterone play a role in promoting EOC growth, metastasis, and progression. Recent data show that ER and PgR expression is frequent in high grade EOC and has prognostic significance. A large meta-analysis showed a clinical benefit with any endocrine treatment, and in particular for aromatase inhibitors (AIs), with a greatere benefit for ER+ and/or PgR+ patients and platinum sensitive tumors. Moreover, the analysis of a few randomized clinical trials (RCTs) showed a reduced mortality with endocrine therapy in EOC, suggesting that ER and PgR have a predictive role and that inhibition of their activation could therefore be a treatment option for EOC.

Exemestane is a well-tolerated and effective AI in endocrine sensitive breast cancer which inhibits the production of Estrogens by the adipose tissue in postmenopausal women.

In this Italian, multicentre, randomized, double-blind, placebo controlled, phase III study will be assessed the efficacy of exemestane versus placebo in addition to the standard front line treatment in patients with high grade serous or endometrioid EOC, IHC positive (≥ 10%) ER or PgR disease, stage IIB - IV according to the FIGO classification.

The primary objective of the study is to test the superiority of exemestane over placebo in addition to the standard front line treatment in terms of PFS.

Secondary Objectives are:

1. to test whether the percent expression of ER and PgR is predictive of the effect of exemestane on PFS;
2. to test whether the addition of exemestane to the standard front line treatment can prolong Overall Survival (OS);
3. to evaluate objective response rate Overall Response Rate (ORR) of experimental treatment compared with the standard one;
4. to assess whether the effect of exemestane is affected by the proliferative index Ki67;
5. to evaluate the effect of exemestane on Quality of Life (QoL);
6. to evaluate the compliance to the study treatment;
7. to evaluate the safety profile of the experimental treatment compared with the standard one.

Study design: a total of 468 subjects (234 per Arm) will be randomized in a 1:1 ratio to receive either standard chemotherapy treatment plus exemestane (Experimental arm) or standard chemotherapy plus placebo (Control arm). Exemestane/placebo will be self-administered as a single oral tablet of 25 mg/day until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first. Radiological disease assessments and CA125 will be performed at baseline and every 4 months from randomization, until end of study or disease progression whichever comes first. Safety assessments will be performed at each cycle during standard chemotherapy treatment, then at each study visit, up to 30 days after the last Experimental Treatment administration.Quality of Life will be assessed by a menopause-specific questionnaire, administered to patients at baseline (T0), at 12 months (T1) and at disease progression (T2). For patients who have signed the specific informed consent, tissues and blood samples will be collected.

Exemestane in Hormone Receptor Positive High Grade Ovarian Cancer

EXemestane in Progesterone and/or Estrogen Receptor Positive Epithelial Ovarian Cancer: A Randomized Phase III Trial, EXPERT

Individual participant data that underlie the results reported in the primary publication of the trial will be shared (text, tables, figures, and appendices), after deidentification.

To collect and store blood and tissue samples to create a bio-bank for the assessment of circulating and tissue biomarkers with potentially prognostic/predictive value, including the androgen receptor (AR) expression and the generation of a somatic genomic and transcriptomic atlas of epithelial ovarian cancers, to map the different molecular vulnerabilities lagging behind the single definition of each histological subtype. Data generated will allow to select molecular biomarkers with prognostic/predictive relevance, to have information of patients risk of relapse or to guide novel treatment approaches.

These biomarker endpoints will be considered in a second phase of the study, if additional funds are available to perform the analyses.

PFS id defined for each patient as the time from the date of randomization to the date of local or regional relapse, distant metastasis, second primary malignancy or death from any cause, whichever comes first. Patients not recurred, progressed or died while on study or lost to follow-up will be censored at their last disease assessment date.

OS is defined for each patient as the time from the date of randomization to the date of death from any cause. Patients not reported as having died at the end of the study will be censored at the date they were last known to be alive.

ORR is defined as the number of patients who will experience a complete or partial response divided by the number of patients randomized with at least one target lesion at baseline. Each patient will be assigned the best response ever recorded during the trial

The effect of study treatment will be assessed based on the MENQOL intervention questionnaire based on 29 items divided in four domains (vasomotor, physical, psychosocial and sexual), each scored from 1 to 8 (1 means no symptom, 2 presence of the symptoms but not bothersome, 3-8 an increasing grade of discomfort). Mean changes from the baseline domain scores between treatment arms will be evaluated.

Number of tablets taken (i.e., number of tablets given-number of tablets returned)/number of tablets that should have been taken during the treatment period.

Maximum toxicity grade experienced by each patient for each toxicity, proportion of patients experiencing grade 3-4 toxicity for each toxicity, type, frequency and nature of serious adverse events (SAEs).

* Proportion of patients with at least one SAE.
* Proportion of patients with at least one serious adverse drug reaction (SADR).

Istituto Di Ricerche Farmacologiche Mario Negri

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Federation of Italian Cooperative Oncology Groups

Ente Ospedaliero Ospedali Galliera

Principal Investigator

Mitogens

Palbociclib

Protein Kinase Inhibitors

Participants will receive Palbociclib 75, 100, 125 milligram (mg) capsules or tablets, orally, once daily from Days 1 to 21 followed by 7 days off treatment in 28-day cycles along with H3B-6545 150, 300, 450 mg capsules or tablets, orally, once daily from Days 1 to 28 in 28-day cycles in dose escalation part. Based on MTD or RP2D determined for H3B-6545 in combination with palbociclib in dose escalation part, participants will continue to receive study treatment in dose expansion part until PD, development of unacceptable toxicity, or withdrawal of consent (up to 24 months).

Palbociclib (75, 100, 125 milligram [mg])

H3B-6545 (150, 300, 450 mg)

The primary objective of this study is to evaluate the safety and tolerability of H3B-6545 and palbociclib when administered in combination in order to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of this combination in women with advanced or metastatic estrogen receptor-positive (ER+) HER2- breast cancer.

A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer

An Open-Label Multicenter Phase 1b Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive HER2-Negative Breast Cancer

Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

The MTD was defined as the highest dose at which no more than 1 of 6 participants experienced a Dose-Limiting Toxicity (DLT) in the dose cohort. DLT was graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs were defined as the following events that occurred in Cycle 1, for which a causal relationship with the study drug could not be ruled out: febrile neutropenia; Grade 4 neutropenia that was not resolved within 7 days; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia lasting greater than (\>) 7 days or associated with clinically significant bleeding; Grade 4 vomiting and diarrhea; Grade 3 vomiting and diarrhea lasting \> 72 hours despite treatment; Grade 4 electrolyte abnormality or Grade 3 abnormality lasting \> 24 hours; Grade 3 or 4 serum creatinine or bilirubin increase; Grade 4 biochemistry or Grade 3 lasting \> 7 days; Grade 4 or Grade 3 or intolerable grade 2 toxicities of any non-hematologic adverse event.

TEAE was defined as an adverse event (AE) with an onset that had occurred after receiving study drug. An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A serious adverse event (SAE) was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Ratio of palbociclib Cmax Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Ratio of palbociclib AUC24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Ratio of palbociclib C24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Ratio of palbociclib Cmax Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Ratio of H3B-6545 AUC24 Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Ratio of H3B-6545 C24 Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

ORR is defined as the percentage of participants achieving a best overall response (BOR) of confirmed partial response (PR) or complete response (CR). The ORR will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

DoR is defined as the time from the date of the first documented CR/PR until the first documentation of disease progression (PD) or death, whichever comes first. The DoR will be assessed according to RECIST version 1.1. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

CBR is defined as the percentage of participants with BOR of PR, CR, or durable stable disease (SD) (duration of SD greater than or equal to 23 weeks). Duration of SD is defined as the time from the date of first dose to the date of the first documentation of disease progression or death, whichever occurs first. It will be calculated for participants whose BOR is SD. The CBR will be assessed according to RECIST version 1.1. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

PFS is defined as the time from the first dose date to the date of the first documentation of PD or death (whichever occurs first). Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

OS is defined as the time from first dose date to the date of death from any cause. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Eisai Inc.

Participants received palbociclib 100 milligram (mg) capsule, orally, once daily (QD) from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.

H3B-6545 300 mg + Palbociclib 100 mg

Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.

H3B-6545 300 mg + Palbociclib 125 mg

Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.

H3B-6545 450 mg + Palbociclib 125 mg

Participants received palbociclib 100 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.

H3B-6545 450 mg + Palbociclib 100

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The Full Analysis Set (FAS) included all participants who received at least one dose of study drug.

Eisai Medical Information

H3B-6545

Participants received palbociclib (100 mg, 125 mg) from Days 1 to 21 followed by H3B-6545 (300 mg, 450 mg), from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.

All Participants

The Dose Evaluable Set (DES) included all participants who were evaluated for DLTs in dose escalation part.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Immunological Response Rate Study of THERATOPE® Vaccine in Metastatic Breast Cancer Patients	NCT00046371	Breast Neoplasm...	THERATOPE® vacc...	18 Years -	Oncothyreon Canada Inc.
Exemestane in Hormone Receptor Positive High Grade Ovarian Cancer	NCT04460807	Ovarian Cancer	Exemestane Placebo oral ta...	18 Years -	Ente Ospedaliero Ospedali Galliera
A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer	NCT04288089	Receptors, Estr... Genes, Erbb-2 Breast Neoplasm...	Palbociclib (75... H3B-6545 (150, ...	18 Years -	Eisai Inc.
A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer	NCT04288089	Receptors, Estr... Genes, Erbb-2 Breast Neoplasm...	Palbociclib (75... H3B-6545 (150, ...	18 Years -	Eisai Inc.
Safety and Immunological Response Rate Study of THERATOPE® Vaccine in Metastatic Breast Cancer Patients	NCT00046371	Breast Neoplasm...	THERATOPE® vacc...	18 Years -	Oncothyreon Canada Inc.

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