Tolerability and Pharmacokinetics of AZD8931 in Patients with Advanced Solid Malignancies.

AZD8931

S. Tjulandin

Serban Ghiorghiu

The main purpose of this study is to explore the safety and tolerability of multiple ascending doses (MAD) of AZD8931 in patients with advanced solid malignancies

Study of AZD8931 in Patients With Advanced Solid Malignancies

A Phase 1, Open-label, Multiple-dose, Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD8931 in Patients With Advanced Solid Malignancies

AstraZeneca

Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

IV once weekly for 3 weeks followed by a week off

Mary Stuart, Dr.

Takayasu Kurata, Dr.

The main purpose of this study is to determine if AZD8931 can be safely administered in Japanese patients alone and in combination with weekly paclitaxel. The study will be conducted in two parts: a monotherapy and a combination part, where safe doses of study treatment will be determined.

Study Assessing Safety and Tolerability of AZD8931 Alone or in Combination With Paclitaxel in Japanese Patients.

A Phase I, Open-label, Multiple-dose, Dose-escalation Study To Assess the Safety and Tolerability of AZD8931 Monotherapy in Japanese Patients With Advanced Solid Malignancies and in Combination With Paclitaxel in Japanese Female Patients With Advanced Breast Cancer

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Micronutrients

Hematinics

Vitamins

Gemcitabine

Docetaxel

Bevacizumab

Carboplatin

Fluorouracil

Androgens

Capecitabine

Vinorelbine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Methotrexate

Vincristine

Cisplatin

Epirubicin

Immunomodulating Agents

Durvalumab

Olaparib

Mitomycins

Mitomycin

Vinblastine

Bicalutamide

Taxane

Alkylating Agents

Vinca Alkaloids

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Poly(ADP-ribose) Polymerase Inhibitors

Androgen Antagonists

Hormones

Hormone Antagonists

Folinic Acid

Folate

Vitamin B9

Arm A1 / Targeted Arm : targeted maintenance from a list of 8 targeted drugs guided by the genomic analysis, AZD2014 tablet per os 50 mg bd, continuous dosing, AZD4547 tablet per os 80 mg bd, 2 weeks on/1 week off, AZD5363 capsule per os 480 mg bd, 4 days on/3 days off, AZD8931 tablet per os 40 mg bd, continuous dosing, selumetinib capsule per os 75 mg bd, continuous dosing, vandetanib tablet per os 300 mg od, continuous dosing, bicalutamide tablet per os 150 od, continuous dosing, olaparib tablet per os 300 mg bd, continuous dosing

Arm B1/ maintenance Standard Chemotherapy Arm : such as Anthracyclines (Doxorubicin or Epirubicin or Liposomal Doxorubicine), Taxanes (Paclitaxel, Docetaxel), Cyclophosphamide, DNA Intercalators (Capecitabine, 5-FU, gemcitabine), Methotrexate, Vinca alkaloids (Vinorelbine, Vinblastine, Vincristine), Platinum based chemotherapies (Carboplatin, Cisplatin), Bevacizumab, Mitomycin C, Eribulin

Arm A2/ Immunotherapy arm: maintenance with MEDI4736 for patient without actionable genomic alterations or non eligible to Targeted substudy 1, MEDI4736 Intra-venous 10 mg/kg, Q2W

Arm B2/ maintenance Standard Chemotherapy Arm : such as Anthracyclines (Doxorubicin or Epirubicin or Liposomal Doxorubicine), Taxanes (Paclitaxel, Docetaxel), Cyclophosphamide, DNA Intercalators (Capecitabine, 5-FU, gemcitabine), Methotrexate, Vinca alkaloids (Vinorelbine, Vinblastine, Vincristine), Platinum based chemotherapies (Carboplatin, Cisplatin), Bevacizumab, Mitomycin C, Eribulin

AZD2014

AZD4547

AZD5363

Selumetinib

Vandetanib

Anthracyclines

Taxanes

cyclophosphamide

DNA intercalators

vinca alkaloids

Platinum based chemotherapies

Mitomycin C

Eribulin

MEDI4736

Fabrice ANDRE, Pr

Open label multicentric phase II randomized trial, using high throughput genome analysis as a therapeutic decision tool, which aims at comparing a targeted treatment administered according to the identified molecular anomalies of the tumor with maintenance chemotherapy (targeted substudy 1) as well as immunotherapy with maintenance chemotherapy in patients without actionable genomic alterations or non eligible to substudy 1 (immune substudy 2).

Screening phase:

New frozen biopsy or an archived frozen sample or ctDNA sample will be sent to the genomic platforms for DNA extraction and genomic analysis (DNA microarrays and Next generation sequencing).

Patients can be considered as pre-eligible for the targeted substudy 1 randomisation phase when both following mandatory conditions have been met: stable or responding disease has been observed (investigator judgment) after 6 to 8 cycles of chemotherapy (or at least after 4 cycles of chemotherapy if stopped for toxicity) and targetable alteration has been identified by the Molecular Tumor Board (MTB).

If not eligible for the substudy 1 randomisation phase, patients can be considered as pre-eligible for the immune substudy 2 randomization phase when both following mandatory conditions are met: stable or responding disease (investigator judgment) is observed after 6 to 8 cycles of chemotherapy (or at least after 4 cycles if treatment was stopped due to toxicity) AND not eligible to randomization in the substudy 1 (because patient had no targetable alteration identified by the Molecular Tumor Board, or failed to have a genomic profile for the tumor \[low tumor cells percentage, technical issue during genomic analysis, etc.\], or a non inclusion criteria that precluded entry into the substudy 1)

Randomization phase:

The mandatory post-chemotherapy wash-out period, of 28 days for 21 or 28 day-cycle chemotherapies or of 15 days for weekly (except monoclonal antibodies) or daily chemotherapies,will provide time to achieve all the required tests and examinations.

The randomization program will allocate the following treatments with a 2:1 ratio in favor of Arm A of the considered substudy:

Substudy 1 : targeted therapies versus standard maintenance chemotherapy

* Arm A1 / targeted arm: targeted maintenance from a list of 8 targeted drugs guided by the genomic analysis, or
* Arm B1 / chemotherapy arm : maintenance chemotherapy (or no antineoplastic treatment in case of toxicity at the time of randomization)

Substudy 2 : immunotherapy versus standard maintenance chemotherapy

* Arm A2 / immunotherapy maintenance arm: MEDI4736 or
* Arm B2 / chemotherapy arm: chemotherapy continued as a maintenance chemotherapy (or no antineoplastic treatment in case of toxicity)

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer

PERSONALIZED MEDICINE GROUP / UCBG UC-0105/1304: SAFIR02_Breast - Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer

To evaluate whether treatment with targeted agents guided by high throughput molecular analysis (CGH array, next generation sequencing) improves progression-free survival as compared to standard maintenance therapy in patients with metastatic Breast Cancer

To evaluate whether treatment with MEDI4736 improves progression-free survival as compared to standard maintenance therapy in patients with metastatic Breast Cancer

To evaluate whether treatment with targeted agents guided by high throughput molecular analysis (CGH array, next generation sequencing) or MEDI4736 improves overall survival as compared to standard maintenance therapy in patients with metastatic Breast Cancer

tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria

Toxicities are graded according to the CTCAE V4

Fondation ARC

UNICANCER

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Pemetrexed

Arm A1/ targeted arm: targeted maintenance from a list of targeted drugs guided by the genomic analysis, AZD2014 tablet per os 50 mg bd, continuous dosing, AZD4547 tablet per os 80 mg bd, 2 weeks on/1 week off, AZD5363 capsule per os 480 mg bd, 4 days on/3 days off, AZD8931 tablet per os 40 mg bd, continuous dosing, selumetinib capsule per os 75 mg bd, continuous dosing, vandetanib tablet per os 300 mg od, continuous dosing, olaparib tablet per os 300 mg bd continuous dosing savolitinib tablet per os 600 mg od continuous dosing

Arm B1/ standard arm pemetrexed Intra venous 500 mg/m², every 3 weeks, standard maintenance left to the investigator's choice

Arm A2/ Immunotherapy arm: maintenance with durvalumab for patient without actionable genomic alterations or non eligible to Targeted substudy 1, durvalumab Intra-venous 10 mg/kg, Q2W

Arm B2/ standard arm pemetrexed Intra venous 500 mg/m², every 3 weeks, standard maintenance left to the investigator's choice

Standard maintenance for squamous NSCLC

Standard maintenance for non squamous NSCLC

savolitinib

Fabrice BARLESI, Pr

Open label multicentric randomized phase II trial, using high throughput genome analysis as a therapeutic decision tool, aimed at comparing a targeted treatment administered according to the identified molecular anomalies of the tumor with a standard treatment (pemetrexed in Non-squamous patients and erlotinib in squamous cells, targeted substudy 1) as well as immunotherapy with maintenance therapy in patients without actionable genomic alterations or non eligible to substudy 1 (immune substudy 2).

Screening phase:

New frozen biopsy or an archived frozen sample or ctDNA sample will be sent to the genomic platforms for DNA extraction and genomic analysis (DNA microarrays and Next generation sequencing).

Patients can be considered as pre-eligible for the targeted substudy 1 randomisation phase when both following mandatory conditions have been met : stable or responding disease has been observed after 4 cycles of chemotherapy (investigator judgment) and targetable alteration has been identified by the Molecular tumor board (MTB).

If not eligible for the substudy 1 randomisation phase, patients can be considered as pre-eligible for the immune substudy 2 randomization phase when both following mandatory conditions are met: stable or responding disease (investigator judgment) is observed after 4 cycles of a platinum-based chemotherapy AND not eligible to randomization in the substudy 1 (because patient had no targetable alteration identified by the Molecular Tumor Board, or failed to have a genomic profile for the tumor \[low tumor cells percentage, technical issue during genomic analysis, etc.\], or a non-inclusion criteria that precluded entry into the substudy 1)

Randomization phase:

The mandatory post-chemotherapy 28-day wash-out period following cycle 4 of chemotherapy will provide time to achieve all the required tests and examinations.

The randomization program will allocate the following treatments with a 2:1 ratio in favor of Arm A of the considered substudy:

Substudy 1 : targeted therapies versus standard maintenance therapy

* Arm A1 / targeted arm: targeted maintenance from a list of 6 targeted drugs guided by the genomic analysis, or
* Arm B1 / standard arm : standard maintenance (pemetrexed in non-squamous and standard practice in squamous NSCLC).

Substudy 2 : immunotherapy versus standard maintenance therapy

* Arm A2 / immunotherapy maintenance arm: MEDI4736 or
* Arm B2 / standard arm : standard maintenance (pemetrexed in non-squamous and standard practice in squamous NSCLC).

SAFIR02_Lung - Efficacy of Targeted Drugs Guided by Genomic Profiles in Metastatic NSCLC Patients

Intergroup Trial UNICANCER UC 0105-1305/ IFCT 1301: SAFIR02_Lung - Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Non-small Cell Lung Cancer

To evaluate whether treatment with targeted agents guided by high throughput molecular analysis (CGH array, next generation sequencing) improves progression-free survival as compared to standard maintenance therapy in patients with metastatic NSCLC

To evaluate whether treatment with MEDI4736 improves progression-free survival as compared to standard maintenance therapy in patients with metastatic NSCLC

To evaluate whether treatment with targeted agents guided by high throughput molecular analysis (CGH array, next generation sequencing) or MEDI4736 improves overall survival as compared to standard maintenance therapy in patients with metastatic NSCLC

Intergroupe Francophone de Cancerologie Thoracique

Digestive System Diseases

Rare Diseases

Stomach Neoplasms

Stomach Cancer

Herbal and Botanical

Trastuzumab

Sage

Placebo

IV once weekly for 3 weeks followed by a week off.

Serban Ghiorghiu, M. D.

The purpose of the study is to assess the efficacy and safety and PK of AZD8931 plus paclitaxel versus paclitaxel alone in patients with metastatic, gastric or gastro-oesophageal junction, cancer.

A Phase IIa Multi-centre Randomised Double-Blind Placebo-controlled Study to Assess the Efficacy, Safety and Pharmacokinetics of AZD8931 in Combination with Paclitaxel versus Paclitaxel alone in Patients with Metastatic, Gastric or Gastro-oesophageal Junction, Cancer who progress following First Line Therapy and are Ineligible for Treatment with trastuzumab by HER2 Status (SAGE)

Assess the Efficacy of AZD8931 in Combination With Paclitaxel Versus Paclitaxel Alone in Patients With Gastric Cancer

A Phase IIa Multi-centre Randomised Double-Blind Placebo-controlled Study to Assess the Efficacy, Safety and Pharmacokinetics of AZD8931 in Combination With Paclitaxel Versus Paclitaxel Alone in Patients With Metastatic, Gastric or Gastro-oesophageal Junction, Cancer Who Progress Following First Line Therapy and Are Ineligible for Treatment With Trastuzumab by HER2 Status (SAGE)

Time from the date of randomization until the date of objective disease progression (as per RECIST1.1) or the date of death (by any cause in absence of progression).

The number of subjects with at least one visit response of CR or PR. (Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD), A ≥ 20% increase in the sum of diameters of target lesions and an absolute increase of ≥ 5mm; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Not Evaluable (NE), All target lesion measurements are missing or \>1/3 target lesion measurements are missing and sum of diameters of non-missing target lesions does not qualify for PD; Not applicable (NA), No target lesions are recorded at baseline)

AZD8931 40 mg bd (Twice daily) administered orally in combination with paclitaxel 80 mg/m2 administered intravenously \[approximately 1 hour duration\] on D1, 8 and 15 of each 28 day treatment cycle

AZD8931 40mg + Paclitaxel

AZD8931 matching placebo bd administered orally in combination with paclitaxel 80 mg/m2 administered intravenously \[approximately 1 hour duration\] on D1, 8 and 15 of each 28 day treatment cycle

Placebo + Paclitaxel

Total

Age, Continuous

18 - < 50 years

50 - < 65 years

65 - < 75 years

>= 75 years

Age, Customized

Sex: Female, Male

Asian

Race/Ethnicity, Customized

Asian (Other Than Chinese or Japanese)

Chinese

Japanese

HER2 0 No staining/membrane staining <10% of cells

HER2 1+ Faint membrane staining ≥10% of cells

HER2 2+ Weak/moderate membrane staining ≥10% cells

HER2 Status (Local Labs): HER2/IHC (Local Assessment)

HER2 Status: HER2/IHC (Local Assessment)

Dr Serban Ghiorghiu

60 patients had been considered to detect a -20% difference in the estimated average percentage change in tumour size at 8 weeks for AZD8931 plus paclitaxel compared to paclitaxel alone at a one-sided significance level of 10% with 90% power. This is based on a standard deviation of 30% for tumour data (on an absolute scale)

AZD8931 + Paclitaxel

Change in Tumour Size at 8 Weeks Were Analyzed for Comparing Relative Efficacy of AZD8931 Plus Paclitaxel With Paclitaxel Alone

Progression-free Survival (PFS) Were Analysed for Comparing Relative Efficacy of AZD8931 Plus Paclitaxel With Paclitaxel Alone

Complete Response

Partial Response

The Objective Response Rate (ORR) Was Analysed for Investigating the Efficacy of AZD8931 Plus Paclitaxel With Paclitaxel Alone

Overall Study

Recurrence

IV once weekly for 3 weeks followed by a week off (repeated cycles)

Professor Jose Baselga

The main purpose of this study is to determine if AZD8931 can improve the efficacy of standard chemotherapy for the treatment of advanced breast cancer. This study will be conducted in 2 parts: the first part (phase I) will determine a dose of AZD8931 that can be safely administered with paclitaxel chemotherapy. The second part (phase II) will determine the efficacy and safety of AZD8931 in combination with paclitaxel chemotherapy in breast cancer.

Phase I/II AZD8931/Paclitaxel in Treatment of Advanced Solid Tumours (Phase I) and Advanced Breast Cancer (Phase II)

A Phase I/II Multi-centre Study of AZD8931 in Combination With Weekly Paclitaxel to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy in Patients With Advanced Solid Tumours and in a Selected Population With Low HER2-expressing Locally Recurrent and/or Metastatic Breast Cancer

DLT is an AE or laboratory abnormality related to AZD8931, starting during the DLT evaluation period and meeting any of the following criteria (further detail in protocol): Symptomatic ocular surface lesion; CTCAE grade 4 haematological AE; CTCAE grade ≥3 of febrile neutropenia / neutropenia / thrombocytopenia / hyperkalaemia / hyperglycaemia / hypotension / urological toxicity / ILD / pneumonitis; QTcF interval \> 500 msec, two ECGs ≥ 30 minutes apart; Symptomatic congestive cardiac failure and a drop in LVEF; Decrease in LVEF of ≥20% to below the LLN; CS rash remaining CTCAE grade ≥3 for ≥5 days despite optimal treatment; CTCAE grade ≥3 nausea, vomiting or diarrhoea, despite optimal therapy; Other CTCAE grade ≥3 toxicity which, in the opinion of the investigator, is CS and related to AZD8931; Delay to the administration of paclitaxel on D1 of Cycle 2 by ≥7 days. Patients could have more than one DLT.

Time from the date of randomization until the date of objective disease progression (as per RECIST 1.1) or the date of death (by any cause in the absence of progression)

The number of subjects with at least one visit response of CR or PR (Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD), A ≥ 20% increase in the sum of diameters of target lesions and an absolute increase of ≥ 5mm; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Not Evaluable (NE), All target lesion measurements are missing or \>1/3 target lesion measurements are missing and sum of diameters of non-missing target lesions does not qualify for PD; Not applicable (NA), No target lesions are recorded at baseline))

The time from the date of randomization until the date of death due to any cause.

In part B, SAEs considered related to study procedures should continue to be collected while patients are followed up for disease progression.

AZD8931 40 mg bd

AZD8931 80 mg bd

Part A: AZD8931 120mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

AZD8931 120 mg bd

Part A: AZD8931 160mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of AZD8931 in Patients With Advanced Solid Malignancies	NCT00637039	Advanced Solid ...	AZD8931	18 Years -	AstraZeneca
Study Assessing Safety and Tolerability of AZD8931 Alone or in Combination With Paclitaxel in Japanese Patients.	NCT01003158	Neoplasms Metastatic Canc... Breast Cancer	AZD8931 Paclitaxel	20 Years -	AstraZeneca
SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer	NCT02299999	Metastatic Brea...	AZD2014 AZD4547 AZD5363 AZD8931 Selumetinib Vandetanib Bicalutamide Olaparib Anthracyclines Taxanes cyclophosphamid... DNA intercalato... Methotrexate vinca alkaloids Platinum based ... Bevacizumab Mitomycin C Eribulin MEDI4736	18 Years -	UNICANCER
SAFIR02_Lung - Efficacy of Targeted Drugs Guided by Genomic Profiles in Metastatic NSCLC Patients	NCT02117167	Non-small Cell ...	AZD2014 AZD4547 AZD5363 AZD8931 Selumetinib Vandetanib Standard mainte... Pemetrexed Durvalumab savolitinib Olaparib	18 Years -	UNICANCER
Assess the Efficacy of AZD8931 in Combination With Paclitaxel Versus Paclitaxel Alone in Patients With Gastric Cancer	NCT01579578	Metastatic, Gas...	AZD8931 Placebo Paclitaxel	18 Years -	AstraZeneca
Study Assessing Safety and Tolerability of AZD8931 Alone or in Combination With Paclitaxel in Japanese Patients.	NCT01003158	Neoplasms Metastatic Canc... Breast Cancer	AZD8931 Paclitaxel	20 Years -	AstraZeneca
Study of AZD8931 in Patients With Advanced Solid Malignancies	NCT00637039	Advanced Solid ...	AZD8931	18 Years -	AstraZeneca
SAFIR02_Lung - Efficacy of Targeted Drugs Guided by Genomic Profiles in Metastatic NSCLC Patients	NCT02117167	Non-small Cell ...	AZD2014 AZD4547 AZD5363 AZD8931 Selumetinib Vandetanib Standard mainte... Pemetrexed Durvalumab savolitinib Olaparib	18 Years -	UNICANCER
Phase I/II AZD8931/Paclitaxel in Treatment of Advanced Solid Tumours (Phase I) and Advanced Breast Cancer (Phase II)	NCT00900627	Neoplasms Breast Neoplasm... Breast Cancer	AZD8931 Paclitaxel Placebo	18 Years - 150 Years	AstraZeneca
Study of Anastrozole +/- AZD8931 in Postmenopausal Women With Endocrine Therapy Naive Breast Cancer	NCT01151215	Neoplasms Breast Neoplasm... Breast Cancer	AZD8931 anastrozole Placebo	18 Years -	AstraZeneca
Phase I/II Trial of Antagonism of HER in GI Cancer	NCT01862003	Metastatic Colo... Recurrent Color...	AZD8931 Irinotecan Folinic Acid Fluorouracil Fluorouracil	16 Years -	University College, London

Spots Global Cancer Trial Database for azd8931

Every month we try and update this database with for azd8931 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for azd8931

Every month we try and update this database with for azd8931 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for azd8931 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.