Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Immune System Diseases

Breast Neoplasms

Hypersensitivity

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Hormones

Estrogens

Mitogens

Participants will take abemaciclib (150mg) orally twice a day and ZN-c5 (dose escalation) orally once or twice a day to determine the safety, tolerability, and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D).

ZN-c5

Abemaciclib (VERZENIO®) is an approved drug.

Abemaciclib

Carrie Brownstein, MD

This is a Phase 1b, open-label, multicenter, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of ZN-c5 administered orally in combination with abemaciclib (VERZENIO®) in participants with advanced estrogen-receptor positive, human epidermal growth factor receptor-2 negative (ER+/HER2-) breast cancer.

All participants will receive the same treatment but ZN-c5 will be given at different doses in this dose escalation study.

A Study of ZN-c5 and Abemaciclib in Participants With Breast Cancer

A Phase 1b Study of ZN-c5 in Combination With Abemaciclib in Patients With Estrogen-Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative Advanced Breast Cancer

Measured by the number of treatment-emergent adverse events and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

Measured by radiographic responses as defined by revised Response Evaluation Criteria in Solid Tumor (RECIST) v1.1.

Zeno Alpha Inc.

Antineoplastic Agents

Palbociclib

Protein Kinase Inhibitors

Enzyme Inhibitors

Dose escalation cohorts are planned to determine maximum tolerated dose(MTD) or recommended phase 2 dose (RP2D) of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Dose escalation cohorts are planned to determine maximum tolerated dose(MTD) or recommended phase 2 dose (RP2D) of ZN-c5 in combination with palbociclib as well as a Phase 2 cohort.

Palbociclib (IBRANCE®) is an approved drug

Zeno Alpha, Inc.

This is a Phase 1/2, open-label, multicenter, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ZN-c5 administered orally in subjects with advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer. ZN-c5 will be evaluated both as monotherapy and in combination with palbociclib (IBRANCE®).

Dose escalation cohorts are planned in monotherapy and combination as well as monotherapy dose expansion, and monotherapy and combination Phase 2.

A Study of ZN-c5 in Subjects With Breast Cancer

A Phase 1/2 Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of ZN-c5 Alone and in Combination With Palbociclib in Subjects With Estrogen-Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative Advanced Breast Cancer

Measured by the number of treatment-emergent adverse events

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Supervised high intensity aerobic and resistance exercise tapering to self management with psychosocial support

Self directed exercise and psychosocial support group

High intensity aerobic and resistance training

Psychosocial support

Robert Newton

Fred Saad

To determine if supervised high intensity aerobic and resistance training increases overall survival compared to self-directed exercise in patients with metastatic prostate cancer.

INTense ExeRcise for surviVAL Among Men With Metastatic Prostate Cancer (INTERVAL - GAP4)

INTense ExeRcise for surviVAL Among Men With Metastatic Prostate Cancer (INTERVAL - GAP4): A Multicentre, Randomised, Controlled, Phase III Study

Overall survival will be measured from the time of randomization until death

Time to disease progression will be measured from randomization until the first of the following: first CT or bone scan documenting disease progression, initiation of a new therapy for mPC (clinical progression), or first occurrence of a Symptomatic Skeletal Related Event (SSE).

Time to first occurrence of SSE will be defined as the time from randomization to documentation of any of the following (whichever occurs first) + 1 day:

* Use of external beam radiation therapy to relieve bone pain
* Occurrence of new symptomatic pathological bone fractures that may be vertebral or non-vertebral. Asymptomatic compression fractures detected by radiology review only will not be considered a SSE.
* Spinal cord compression
* Change in antineoplastic therapy to treat bone pain
* Surgical intervention to treat bone pain

Opiate use will be assessed via BPI-SF, the medical record review at entry with a lead-in period (\<28 days). The questionnaires will be administered every three cycles until month 24, and in month 36.

Analgesic use will be assessed via BPI-SF, the World Health Organisation (WHO) analgesic scale, and medical record review at entry with a lead-in period (\<28 days). The WHO analgesic scale will be completed every three cycles (based on medical review) and questionnaires will be administered every three cycles until month 24, and in month 36.

Inflammatory and cytokine systemic milieu

Physical and emotional quality of life measured by the questionnaires- Functional Assessment of Cancer Therapy- Prostate (FACT-P), Functional assessment of Chronic Illness Therapy (FACIT-Fatigue), and EuroQOL Five Dimension Questionnaire (EQ5D) will be assessed every 3 cycles.

Physical function will be assessed using strength assessments (1RM), a cardiopulmonary exercise test (CPET) and a functional performance test (400m walk)

Pain will be assessed via questionnaire Brief Pain Inventory- short form (BPI-SF) and medical record review at entry with a lead-in period (\<28 days) and repeated measures will occur every three cycles

University of California, San Francisco

Edith Cowan University

King's College London

Centre hospitalier de l'Université de Montréal (CHUM)

Movember Foundation

Symptoms and General Pathology

Neoplasm Metastasis

Androgens

Pluvicto

Radiopharmaceuticals

2 (+2) cycles of 7.4 GBq 177Lu-PSMA 6 weeks in between

Deferred androgen deprivation therapy. However, the control arm can receive the study drug (177Lu-PSMA) in case of disease progression (defined in the study protocol).

177Lu-PSMA-617

Bastiaan Privé, MD PhD

Michel de Groot

Alexis Vrachimis, MD PhD

Daniela Oprea-Lager, MD PhD

Walter Noordzij, MD PhD

James Nagarajah, MD PhD

James Nagarajah, Prof.

Radioligand therapy (RLT) using Lutetium-177 labelled PSMA is a promising new therapeutic approach to treat metastatic prostate cancer. This tumor-specific treatment is directed against prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer cells. In the last few years, several lutetium-177 (177Lu, β emitter) labeled PSMA ligands have been developed and are currently applied to treat metastatic castrate resistant prostate cancer patients. To date, there are no prospective randomized studies published using this treatment in the hormone sensitive setting or in oligometastatic prostate cancer. Therefore, this study we will evaluate the effect of 177Lu-PSMA in patients with hormone sensitive oligo-metastatic prostate cancer.

Prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a promising new therapeutic approach to treat metastatic prostate cancer. This tumor-specific treatment is directed against PSMA, which is overexpressed in prostate cancer cells. In the last few years, several Lutetium-177 (177Lu, β emitter) labeled PSMA ligands have been developed and are currently applied in nuclear medicine departments worldwide to treat metastatic castrate resistant prostate cancer (mCRPC) patients.

A large retrospective study reported an overall biochemical response rate of 45% following multiple 177Lu-PSMA RLT cycles in mCRPC patients, while 40% of patients already responded after a single cycle. RLT with 177Lu-PSMA was generally well tolerated and 12% of the patients suffered grade 3 to 4 hematological toxicity. In addition, mild and often transient xerostomia occurred in 8%. A prospective study carried out in Australia confirmed these results recently. Based on these outcomes Endocyte (a Novartis company) is currently carrying out an international multicenter prospective registration study for end-stage mCRPC patients (NCT03511664).

Although these results are promising, it is noteworthy that most of the currently available data is retrospective and 177Lu-PSMA has only been evaluated in end stage prostate cancer patients to date. However, based on the mode of action, 177Lu-PSMA could also be effective in low volume disease because of the very high tumor uptake of radioligands in smaller lesions. Also, in a pilot study (NCT03828838) we were able to show that 177Lu-PSMA treatment is safe coupled with promising response rates. Hence, the present randomized trial to investigate the efficacy of 177Lu-PSMA in patients with oligo-metastatic (≤5 metastases) metastatic prostate cancer, prior to the hormone insensitive state. In this study, 58 patients will be included in a 1:1 ratio to receive either 177Lu-PSMA or the current standard of care (deferred androgen deprivation therapy).

At the end of the study period for answering the primary research question, patients randomized to the control arm are eligible to receive 177Lu-PSMA if they meet the end of the study period treatment (EOT 1) criteria and are willing to undergo 177Lu-PSMA.

EOT 1 is defined by:

* Clinical progression determined by the treating physician (e.g. increasing pain from metastases)
* A 100% increase in PSA after cycle one blood draw (BASELINE) during study. Exception: PSA increase in the first 12 weeks after the first treatment injection as was defined by the PCWG3 criteria.

Randomized, two-arm, open label, multi-center, phase II study

Lutetium-177-PSMA-617 in Oligo-metastatic Hormone Sensitive Prostate Cancer

Lutetium-177-PSMA-617 Radioligand Therapy in Oligo-metastatic Hormone Sensitive Prostate Cancer.

Disease progression (EOT 1) is defined by:

* A 100% increase in PSA after cycle one blood draw (BASELINE) during study. Exception: PSA increase in the first 12 weeks after the first treatment injection as was defined by the PCWG3 criteria. Or;
* Clinical progression determined by the treating physician (e.g. increasing pain from metastases).

The change in PSA after 177Lu-PSMA and proportion of achieving a ≥ 50% decrease in PSA from baseline.

The changes in uptake (SUVmax) of 18F-PSMA PET/CT before and 6 months after 177Lu-PSMA.

The size of soft tissue metastases on 18F-PSMA PET/CT and (whole body) MRI after 177Lu-PSMA.

Clinical progression is defined by the treating physician (e.g. increasing pain from metastases). PSA progression is defined as a ≥ 25% increase in PSA from nadir, with a minimum PSA of \>0,5 µg/l and which is confirmed by a second value ≥ 3 weeks later (i.e. confirmed rising trend). Within the first 12 weeks after treatment administration PSA increases will be ignored in the absence of other evidence of disease progression due to the flare phenomenon. If no decline occurs, date of ≥ 25% increase will be recorded. Radiographic progression is defined by the amount and size of the lesions. Where applicable PCWG3 and RECIST v1.1 criteria will be followed.

The following questionnaires will be used: EORTC QLQ-C30, QLQ-PR25 \& xerostomia inventory.

Prostaatkankerstichting

Advanced Accelerator Applications

Radboud University Medical Center

Menopause

Bone Density Conservation Agents

Reproductive Control Agents

Tamoxifen

Letrozole

Triptorelin Pamoate

Zoledronic Acid

Aromatase Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Contraceptive Agents

Contraceptive Agents, Female

Contraceptive Agents, Hormonal

Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years

Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years

Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.

tamoxifen

Premenopausal patients will receive triptorelin 3.75 mg IM at the beginning of therapy and every 4 weeks for 5 years or up to age 55

triptorelin

letrozole

zoledronic acid

Andrea De Matteis, M.D.

Ciro Gallo, M.D., Ph.D.

Francesco Perrone, M.D., Ph.D.

The HOBOE study was amended in November 2009, and, after reaching enrollment of the first 500 patients, the study began recruiting premenopausal patients only. The primary objective of the extended study is to compare disease free survival in premenopausal patients with early breast cancer. Patients receive triptorelin and are randomized in a 1:1:1 fashion to receive tamoxifen or letrozole, or letrozole + zoledronic acid.

The purpose of the HOBOE study, Version 1, was to compare the adjuvant hormonal therapy treatments of Tamoxifen, Letrozole and Letrozole + Zoledronate for their effects on bone loss in breast cancer patients. Postmenopausal and premenopausal patients were eligible, the latter also receiving monthly triptorelin. Upon reaching the enrollment of the first 500 patients in March 2010, the study began recruiting premenopausal patients only.

HOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer.

Phase III Randomized Study of the Effects on Bone Mineral Density of Tamoxifen, Letrozole, and Letrozole + Zoledronic Acid as Adjuvant Treatment of Patients With Early Breast Cancer; VERSION 2 AMENDED Phase 3 Study of Triptorelin and Tamoxifen, Letrozole, or Letrozole + Zoledronic Acid in Adjuvant Treatment of Premenopausal Endocrine Responsive Breast Cancer Patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of ZN-c5 and Abemaciclib in Participants With Breast Cancer	NCT04514159	Breast Cancer	ZN-c5 Abemaciclib	18 Years -	Zeno Alpha Inc.
A Study of ZN-c5 in Subjects With Breast Cancer	NCT03560531	Breast Cancer	ZN-c5 Palbociclib	18 Years -	Zeno Alpha Inc.
INTense ExeRcise for surviVAL Among Men With Metastatic Prostate Cancer (INTERVAL - GAP4)	NCT02730338	Metastatic Pros...	High intensity ... Psychosocial su...	18 Years -	Movember Foundation
INTense ExeRcise for surviVAL Among Men With Metastatic Prostate Cancer (INTERVAL - GAP4)	NCT02730338	Metastatic Pros...	High intensity ... Psychosocial su...	18 Years -	Movember Foundation
Lutetium-177-PSMA-617 in Oligo-metastatic Hormone Sensitive Prostate Cancer	NCT04443062	Prostate Cancer	177Lu-PSMA-617	18 Years -	Radboud University Medical Center
HOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer.	NCT00412022	Breast Cancer	tamoxifen triptorelin letrozole zoledronic acid	18 Years -	National Cancer Institute, Naples
INTense ExeRcise for surviVAL Among Men With Metastatic Prostate Cancer (INTERVAL - GAP4)	NCT02730338	Metastatic Pros...	High intensity ... Psychosocial su...	18 Years -	Movember Foundation

Spots Global Cancer Trial Database for hormone sensitive