Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Carboplatin

Antimetabolites

gemcitabine

carboplatin

Volker Heinemann, MD

The rational for this trial is given by the knowledge that gemcitabine acts as a potent inhibitor of DNA repair and therefore may prevent adequate repair of platin-induced DNA damage. Gemcitabine is an excellent choice for combination therapy by its unique mechanism of action and favourable toxicity profile. The combination of gemcitabine and cisplatin was shown to be effective in several trials, producing response rates of 30-52 % in patients with pretreated metastatic breast cancer. To improve on tolerability and handling of the regime carboplatin may be the more appropriate choice for treatment. The mechanism of action of carboplatin is very similar to that of cisplatin. The rational for combining gemcitabine and carboplatin is based on their single-agent activities in metastatic breast cancer, the activity of this combination in other malignancies and on the fact that carboplatin has demonstrated efficacy comparable with cisplatin in several tumor types.

Gemcitabine + Carboplatin in Breast Cancer

Gemcitabine Plus Carboplatin in Patients With Pretreated Metastatic Breast Cancer

Eli Lilly and Company

Ludwig-Maximilians - University of Munich

Capecitabine

Bendamustine Hydrochloride

Taxane

Antineoplastic Agents, Alkylating

Alkylating Agents

Capecitabine will be dosed at 1000mg/m2 twice daily for 14 days, followed by a 7-day rest period for a total cycle time of 21 days (until disease progression or unacceptable toxic effects).

Bendamustine 80mg/m2 will be administered on day 1 and 8 of a three week cycle (for a maximum of eight cycles).

Eligible patients will receive capecitabine in combination with bendamustine for a maximum of eight cycles and afterwards capecitabine mono will be continued until disease progression or unacceptable toxic effects. Safety assessments will be conducted in 3-weekly intervals; efficacy assessments will be conducted every 9 weeks.

Capecitabine will be dosed at 1000mg/m2 twice daily for 14 days, followed by a 7-day rest period for a total cycle time of 21 days (until disease progression or unacceptable toxic effects).

Bendamustine 80mg/m2 will be administered on day 1 and 8 of a three week cycle (for a maximum of eight cycles).

Bendamustine

Richard Greil, Prof.Dr.

Patients with pretreated, Her2-negative, advanced breast cancer will receive chemotherapy with capecitabine and bendamustine for a maximum of eight cycles and afterwards capecitabine alone until disease progression or unacceptable toxic effects. Safety assessments will be conducted in 3-weekly intervals, efficacy assessments (CT or MRI) will be conducted every 9 weeks.

Aim of this study is to determine whether treatment with capecitabine in combination with bendamustine is efficacious and safe.

40 eligible patients will be enrolled. A two-stage design efficacy and safety of bendamustine and capecitabine will be evaluated following recruitment of the first 20 patients. Upon favorable results a further 20 patients will be recruited to reach the target population of 40 evaluable patients.

Pretreatment for eligible patients must include anthracyclines and/or taxanes.

Capecitabine + Bendamustine in Women With Pretreated Locally Advanced or Metastatic Her2-negative Breast Cancer

Capecitabine in Combination With Bendamustine in Women With Pretreated Locally Advanced or Metastatic Her2-negative Breast Cancer, a Phase II Trial

Overall response rates (complete or partial response, determined by radiologic evaluation according to Response Evaluation Criteria in Solid Tumors - RECIST (Response Evaluation Criteria In Solid Tumors) Version 1.1) The study will be stopped after 20 patients if there are fewer than four subjects with an overall response of CR (complete response) or PR (partial response). If there are at least four responses an additional 20 subjects will be enrolled and treated till a maximum of 40 subjects. The regimen is concluded to be effective if 13 or more responses out of 40 are observed at the end of the trial.

The last patient is expected to enter the study in Q1 2015, following a 24 month recruitment period. Last Subject Last Visit will be at final staging after end of treatment of last patient. Follow-up after Last Subject Last Visit will be conducted according to local standard of care thereafter, and is not part of study procedures.

To determine the safety profile of a combination with capecitabine and bendamustine in terms of qualitative and quantitative toxicities from first study treatment dose until completion of study treatment due to progression or for any other reason. All safety analyses will be based on the safety population, defined as subjects who received at least one dose of the study medication and have at least one post-treatment safety assessment available. The safety population will be used for all safety and tolerability analyses including demographic data, vital signs, laboratory data and adverse events.

CR, PR or stable disease for at least 24 weeks

explorative, from treatment start until death from any cause

To evaluate Quality of Life (QoL) status within the study population using the EORTC (European Organisation for Research and Treatment of Cancer) QLQ (Quality-of-life-questionnaire)-C30 standard questionnaire and the BR23 module (module for breast cancer patients)

Predefined subgroup analysis of triple-negative patients and hormone receptor positive patients in terms of response

Arbeitsgemeinschaft medikamentoese Tumortherapie

Symptoms and General Pathology

Nervous System Diseases

Neoplasm Metastasis

Meningeal Carcinomatosis

Neoplasms, Second Primary

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Trastuzumab

Trastuzumab deruxtecan

Hormones

Estrogens

Mitogens

Progesterone

Antineoplastic Agents, Immunological

Immunoconjugates

Immunologic Factors

* Cohort 1: HER2-positive BC with non-progressing BM (after WBRT and/or SRS and or surgery.);
* Cohort 2: HER2-positive or HER2-low BC with asymptomatic untreated BM;
* Cohort 3: HER2-positive BC with progressing BMs after local treatment;
* Cohort 4: HER2-low expressing BC with progressing BMs after local treatment;
* Cohort 5: HER2-positive or HER2-low expressing BC with LMC.

After having confirmed eligibility and entered into the clinical trial, patients will be treated with trastuzumab deruxtecan (DS-8201a) at 5.4 mg/Kg administered as an intravenous (IV) infusion on Day of 21-day cycle (Q3W), initially for at least 90 minutes, then, if there is no infusion-related reaction, for a minimum of 30 minutes.

In patients with hormone receptor (HR)-positive status (estrogen receptor \[ER\] and/or progesterone receptor \[PgR\]) administration of endocrine therapy is not allowed.

In patients allocated in study cohort 5, administration of intrathecal therapy is not allowe

Marta Vaz Batista, MD

This is a multicenter, international, open-label, single-arm, multicohort, two-stage optimal Simon's design, phase II clinical trial

Pretreated, unresectable locally advanced or metastatic Human Epidermal Growth Factor Receptor 2 (HER2)-positive or HER2-low expressing breast cancer (BC) with untreated or treated brain metastases (BMs) or leptomeningeal carcinomatosis (LMC).

This is a multicenter, international, open-label, single-arm, multicohort, two-stage optimal Simon's design, phase II clinical trial.

After confirmed eligibility, patients will be assigned to one of the following five study cohorts:

* Cohort 1: HER2-positive BC with non-progressing BM (after WBRT and/or SRS and or surgery.);
* Cohort 2: HER2-positive or HER2-low BC with asymptomatic untreated BM;
* Cohort 3: HER2-positive BC with progressing BMs after local treatment;
* Cohort 4: HER2-low expressing BC with progressing BMs after local treatment;
* Cohort 5: HER2-positive or HER2-low expressing BC with LMC

DS-8201a for trEatment of aBc, BRain Mets, And Her2[+] Disease

Multicenter, Open-Label, Single-Arm, Multicohort Phase II Clinical Trial of Trastuzumab Deruxtecan(DS-8201a) in Human Epidermal Growth Factor Receptor 2 HER2+ Advanced Breast Cancer With Brain Metastases and/or Leptomeningeal Carcinomatosis

Overall change from baseline in patient-reported global health status/quality of life (GHS/QoL), functioning and symptoms; Time to deterioration in global QoL; Time to deterioration in pain; Time to next therapy.

Relationship between tissue- and/or blood- and/or CSF-based biomarkers and patient clinical characteristics (e.g., baseline features) and outcome (e.g., duration of PFS).

To assess efficacy -defined as 16 weeks progression-free survival (PFS)- per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of trastuzumab deruxtecan (DS-8201a) in patients with pretreated unresectable locally advanced or metastatic HER2-positive BC with non-progressing BM (after WBRT and/or SRS and or surgery). 16 weeks-PFS, defined as the period of time from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first during at least first 6 months. Progression will be determined locally by the investigator through the use of Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria for intracranial (IC) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

To assess efficacy -defined as intracranial overall response rate (ORR-IC) per RANO-BM of trastuzumab deruxtecan (DS-8201a) in patients with pretreated unresectable locally advanced or metastatic BC:

1. HER2-positive or HER2-low expressing with untreated BMs (Cohort 2);
2. HER2-positive with progressing BMs after local treatment (Cohort 3);
3. HER2-low expressing with progressing BMs after local treatment (Cohort 4).

ORR-IC, defined as a complete response (CR) or partial response (PR), and determined locally by the investigator through the use of RANO-BM criteria.

To assess efficacy -defined as OS- of trastuzumab deruxtecan (DS-8201a) in patients with pretreated unresectable locally advanced or metastatic HER2-positive or HER2-low expressing BC with LMCOS defined as the time from treatment initiation to death from any cause. Patients without documented death at the time of the final analysis will be censored at the date of the last follow-up

ORR, defined as a complete response (CR) or partial response (PR), determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST criteria v. 1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

CBR, defined as an objective response (CR or PR), or stable disease (SD) for at least 24 weeks, determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

TTR, defined as the time from the treatment initiation to time of the first objective tumor response observed for patients who achieved a CR or PR, determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

OS, defined as the time from treatment initiation to death from any cause. Patients without documented death at the time of the final analysis will be censored at the date of the last follow-up.

PFS, defined as the period of time from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first. Progression will be determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

Best percentage of change from baseline in the size of CNS lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, and determined locally by the investigator through use of RANO-BM criteria.

Patient safety and adverse events (AEs) will be evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. All AEs and serious adverse events (SAEs) will be assessed to determine the safety and tolerability of the treatment.

PFS, defined as the period of time from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first. Progression will be determined locally per RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

ORR, defined as a CR or PR, determined locally by the investigator through the use of RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

CBR, defined as an objective response (CR or PR), or SD for at least 24 weeks, determined locally by the investigator through the use of RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

TTR, defined as the time from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR, determined locally by the investigator through the use of RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, determined locally by the investigator through the use of RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

OS, defined as the time from treatment initiation to death from any cause. Patients without documented death at the time of the final analysis will be censored at the date of the last follow-up

Best percentage of change from baseline in the size of tumor lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, and determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

Time to WBR and/or SRS (only for cohort 2), defined as the time from the treatment initiation to time of CNS disease progression that requires treatment with WBR and/or SRS, and determined locally by the investigator through the use of RANO-BM criteria and RECIST criteria.

Patient safety and AEs will be evaluated using the NCI-CTCAE v.5.0. All AEs and SAEs will be assessed to determine the safety and tolerability of the treatment.

CNS ORR, defined as a CR or PR, determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

CBR, defined as an objective response (CR or PR), or SD for at least 24 weeks, determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

TTR, defined as the time from the treatment initiation to time of the first objective tumor response observed for patients who achieved a CR or PR, determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions.

Best percentage of change from baseline in the size of tumor lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, and determined locally by the investigator through the use of RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for both extracranial lesions and overall (IC and extracranial) lesions

Daiichi Sankyo

MedSIR

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

Hematinics

Vitamins

Pemetrexed

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Arm A : Gemcitabine: 1000 mg/m2 by intravenous infusion over an exact period of 30' (preferably by a pump to guarantee a constant speed of infusion) on day 3 of each cycle repeated every 14 days.

Pemetrexed: 150 mg/m2 by intravenous continuous infusion over an exact period of 8h on day 1 of each cycle repeated every 14 days.

Gemcitabine: 1000 mg/m2 by intravenous infusion over an exact period of 30' (preferably by a pump to guarantee a constant speed of infusion) on day 3 of each cycle repeated every 14 days.

Pemetrexed: 150 mg/m2 by intravenous continuous infusion over an exact period of 8h on day 1 of each cycle repeated every 14 days.

Arm A : Gemcitabine + Pemetrexed

Giovanni Luca Frassineti, MD

Study Design:

Multicenter, non randomized, open label phase II study designed to evaluate the efficacy and safety of Gemcitabine/Pemetrexed combination.

Enrollment period: 18 months. Treatment period: maximum for 24 weeks for each patient (12 cycles lasting 2 weeks).

Total duration of the study: 24 months.

Number of Subjects:

Approximately 38 subjects will be enrolled on study:

- First stage:12 patients enrolled

If 1 or 0 responses were observed, the trial had to be terminated:

- Second stage: an additional of 23 patients were to be enrolled. If 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.

A Phase II Study to evaluate activity and toxicity of Gemcitabine in Combination with Pemetrexed long term infusion in the Treatment of pretreated Metastatic Colorectal Cancer Patients

Study Design:

Multicenter, non randomized, open label phase II study designed to evaluate the efficacy and safety of Gemcitabine/Pemetrexed combination.

Study Duration

Enrollment period: 18 months. Treatment period: maximum for 24 weeks for each patient (12 cycles lasting 2 weeks).

Total duration of the study: 24 months.

Primary objective:

- objective response rate (ORR: CR+PR+SD)

Secondary objectives:

* safety profile of the drugs combination;
* time to progression (TTP) and overall survival (OS)

Number of Subjects:

Approximately 38 subjects will be enrolled on study:

- First stage:12 patients enrolled

If 1 or 0 responses were observed, the trial had to be terminated:

- Second stage: an additional of 23 patients were to be enrolled. If 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.

Statistical Methodology:

A minimax two-stage Simon design will be employed. A 10% response will preclude further study, whereas a 30% response rate will indicate that further study would be warranted. Using α and β errors of 0.10 and 0.10, respectively, 12 patients will be enrolled in the first stage, and if 1 or 0 responses were observed, the trial had to be terminated. Otherwise, an additional of 23 patients were to be enrolled, and if 5 or less responses were observed in 35 patients, the combination would not be considered worthy of further study, while if 6 or more responses were observed, the combination would be considered sufficiently active to warrant further testing. Taking into account an invalidity rate of 5%, 38 patients will be needed for this step.

The first 6 enrolled patients will be closely controlled for safety and further patients will be enrolled only in absence of severe toxicity resulting in discontinuation 1 month after the first cycle of the six patients.

The primary analysis will be performed on the ITT (Intention To Treat) population. PFS and OS will be estimated by the Kaplan-Meier method. The HR for PFS and OS will be estimated according to the Cox model, with its relative 95% confidence.

A secondary analysis will be performed on the PP (per-protocol) population. The Overall Response Rate to study treatment will be reported on the ITT and PP population with 95% confidence interval. Results will be tabulated and not evaluable patients will be included as additional category.

Gemcitabine in Combination With Pemetrexed Long Term Infusion in the Treatment of Pretreated Metastatic Colorectal Cancer Patients

A Phase II Study to Evaluate Activity and Toxicity of Gemcitabine in Combination With Pemetrexed Long Term Infusion in the Treatment of Pretreated Metastatic Colorectal Cancer Patients

Determination of the objective response rate (ORR: CR (complete response) +PR (partial response) +SD (stable disease)) of treated patients according to RECIST criteria

Assessment of safety profile of study drug combination in patients treated: report of Adverse Events according to the The NCI's Common Toxicity Criteria version 4.0

Determination of Time to Progression (TTP) of treated patients

Determination of Overall Survival (OS) of treated patients

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Alemtuzumab

Dose escalation phase:

Days -3, -2, -1: 3 - 10 - 30 mg Alemtuzumab s.c.

Treatment phase:

Bendamustine 70 mg/m2 i.v. on d1 + d2 repeat every 28 days for 4 cycles

Alemtuzumab 30 mg s.c. 3x per week (days 1, 3, 5) continuously in parallel with chemotherapy cycles for a maximum of 16 weeks

The primary objective of this study is to determine the percentage of patients achieving a response, defined as the percentage of patients achieving complete response, partial response and stable disease/ no change upon treatment with the combination therapy according to NCI response criteria (also established according to IWCLL guidelines) upon treatment with a combination of bendamustine and alemtuzumab.

This is a non-randomized, multicenter, open-label, single-arm Phase I/II study to evaluate the safety and efficacy of bendamustine combined with alemtuzumab in patients with pretreated CD20-positive CLL (according to the revised NCI/ IWCLL criteria).

Eligible patients will receive bendamustine as 4 courses of 70 mg/m2 on days 1 and 2 every 28 days and 30 mg alemtuzumab s.c. continuously on days 1, 3 and 5 of every week, for a maximum of 16 weeks. Safety assessments will be conducted weekly; efficacy assessments including imaging will be performed at months 2, 4, 6, 10 and 16. Bone marrow biopsies will be performed upon CR (according to the 2008 IWCLL response criteria) or fixed at 6 and 16 months.

Following recruitment of the first 3 and 7 patients safety evaluations will be performed by a data safety monitoring board. An interim analysis for response and safety as well as maximum tolerated dose levels will occur after the first 7 patients have completed treatment (Gehan timepoint). If the treatment is deemed clinically safe a further 13 patients will be enrolled.

Bendamustine Combined With Alemtuzumab in Pretreated Chronic Lymphocytic Leukemia (CLL)

Bendamustine Combined With Alemtuzumab in Pretreated Chronic Lymphocytic Leukemia (CLL) - A Phase I/II Trial With Concomitant Evaluation of Safety and Efficacy

Mundipharma Pte Ltd.

Antiemetics

Gastrointestinal Agents

Emetics

Dose escalation step Dose escalation will be conducted on the grid defined by the 4 doses of PLX038 (800 mg/m², 1000 mg/m², 1300 mg/m² and 1700 mg/m² IV every 21 days D1=D22) and 3 doses of Tuvusertib (90 mg, 130 mg and 180 mg QD for 10 days from D3, D3-12). Premedication with anti-emetic agents is not required prior to the initial infusion, but may be used for an individual patient, as needed.

Expansion cohorts Two expansion cohorts are planned, investigating the efficacy and safety in pre-specified populations of interest.

Patients will be treated at the RP2D; 25 evaluable patients are needed in each cohort, to account for possible non evaluable patients, up to 28 patients will be enrolled in each cohort.

Patients enrolled in the phase I part at the RP2D and fulfilling the eligibility criteria of one of the expansion cohorts will be counted in those 25 evaluable patients.

Dose escalation will be conducted on the grid defined by the 4 doses of PLX038 (800 mg/m², 1000 mg/m², 1300 mg/m² and 1700 mg/m² IV every 21 days D1=D22) and 3 doses of Tuvusertib (90 mg, 130 mg and 180 mg QD for 10 days from D3, D3-12). Premedication with anti-emetic agents is not required prior to the initial infusion, but may be used for an individual patient, as needed.

All included patients will receive PLX038 + Tuvusertib until progression of disease, unacceptable toxicity, patient withdrawal of consent, investigator decision, lost to follow-up, death, patient non-compliance, or study termination by Sponsor.

PLX038 + Tuvusertib

Fouzia Azzouz

François-Clément Bidard, Study Principal Investigator

François-Clément BIDARD

Phase I with a dose finding cohort, followed by expansion cohorts in pre-specified tumor types.

This is an open label, multi-centric phase I with, first, a dose escalation step using an adaptation of the Bayesian Optimal INterval (BOIN) drug-combination, followed by 2 dose expansion cohorts using the Simon 2-stage design.

Dose escalation step Dose escalation will be conducted on the grid defined by the 4 doses of PLX038 (800 mg/m², 1000 mg/m², 1300 mg/m² and 1700 mg/m² IV every 21 days D1=D22) and 3 doses of Tuvusertib (90 mg, 130 mg and 180 mg QD for 10 days from D3, D3-12). Premedication with anti-emetic agents is not required prior to the initial infusion, but may be used for an individual patient, as needed.

starting combination level is c1 (PLX038 800mg/m2 and Tuvusertib 90mg). Groups of 3 patients will be sequentially enrolled. One week between the enrollment of the 1st patient and the 2 following patients is mandatory at a new combination level. The decision to (de)-escalate one of the two agents depends on the outcome of all patients treated at the current combination.

Expansion cohorts Two expansion cohorts are planned, investigating the efficacy and safety in pre-specified populations of interest.

Patients will be treated at the RP2D; 25 evaluable patients are needed in each cohort, to account for possible non evaluable patients, up to 28 patients will be enrolled in each cohort.

Patients enrolled in the phase I part at the RP2D and fulfilling the eligibility criteria of one of the expansion cohorts will be counted in those 25 evaluable patients.

A Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) in Patients With Advanced Solid Tumors

A Phase I Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) With Dose Expansion Cohorts in Patients With Advanced Solid Tumors

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

Dose limiting toxicities (DLTs) experienced during 21 days from the first IV infusion of PLX038 + Tuvusertib

Best tumor response (defined as PR or CR in the first 6 months of treatment, assessed by investigators per RECIST v1.1 criteria)

Serious Adverse Events (SAEs) according to NCI CTCAE v5.0 by grade and their relationship to PLX038 + Tuvusertib.

Adverse Events (AEs) according to NCI CTCAE v5.0 by grade and their relationship to PLX038 + Tuvusertib.

Maximum Plasma Concentration effect of PLX038, SN38 and Tuvusertib

ORR defined as the percentage of patients with complete response (CR) or partial response (PR), as the best response measured at the disease assessmement after initiation of treament according to RECIST v1.1

TTR calculated from the initiation of treatment to best tumour response (CR/PR)

DoR defined as the time period from best tumour response to disease progression (according to RECIST v1.1)

PFS measured from the inclusion in the study to the first documented progression (according to RECIST v1.1) or death from any cause.

DoR defined as the time period from best tumour response to disease progression

PFS measured from the inclusion in the study to the first documented progression

OS is defined as the time from inclusion to the event death.

Association between PLX038 + Tuvusertib efficacy and homologous recombination (HR) defect (assessed by HR genes mutational status and BCRAness phenotype), replication stress-related biomarkers such as SFLN11 expression, RB1 loss; genomic alterations in DDR genes

Association between PLX038 + Tuvusertib efficacy and quantitative changes of blood biomarkers (e.g. ctDNA) during therapy.

ProLynx LLC

Merck Sharp & Dohme LLC

Institut Curie

Triple Negative Breast Neoplasms

Patients will be treated at a dose of 1730mg/m2 IV infusion on Day 1 of each cycle Q3W (every 21 days, 1 cycle = 1 injection) after at least a first cycle at 1300mg/m2. At the discretion of the treating physician, the PLX038 dose will be increased to 1730 mg/m2 for patients who tolerate at least 1 cycle without any of the following toxicities: febrile neutropenia, grade 4 neutropenia for \> 5 days or ANC \< 100 109/L for more than 1 day, or other non-hematological toxicities of Grade \> 2 \[NCI-CTCAE, Version 5\].

Study treatment will be at a dose of 1730mg/m2 IV infusion on Day 1 of each cycle Q3W (every 21 days, 1 cycle = 1 injection) after at least a first cycle at 1300mg/m2.

Patients with a clinical benefit could be treated as long as study is ongoing. Patients are followed from inclusion until documented disease progression, withdrawal of consent, or death.

PLX038

François-Clément Bidard

Single arm phase II study for with primary objective to evaluate the efficacy of PLX038 on response rate for patients with pretreated, metastatic or locally advanced triple negative breast cancer.

This is an open label, multi-centric phase II study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of PLX038 in locally-advanced or metastatic TNBC. Patient must have received prior therapy (administered in the neoadjuvant, adjuvant and/or metastatic setting) with an anthracycline, taxane and sacituzumab-govitecan (unless not medically appropriate or contraindicated for the patient) and Received a minimum of two prior cytotoxic chemotherapy regimens for locally advanced or metastatic breast cancer.

Patients will be treated at a dose of 1730mg/m2 IV infusion on Day 1 of each cycle Q3W (every 21 days, 1 cycle = 1 injection) after at least a first cycle at 1300mg/m2. At the discretion of the treating physician, the PLX038 dose will be increased to 1730 mg/m2 for patients who tolerate at least 1 cycle without any of the following toxicities: febrile neutropenia, grade 4 neutropenia for \> 5 days or ANC \< 100 109/L for more than 1 day, or other non-hematological toxicities of Grade \> 2 \[NCI-CTCAE, Version 5\].

All included patients will receive PLX038 as single agent as long as study is ongoing or until progression of disease, unacceptable toxicity, patient withdrawal of consent, Investigator decision, lost to follow-up, death, patient non-compliance, or study termination by Sponsor.

Tumor assessments must be performed according to the RECIST V1.1 criteria at inclusion and every 8 weeks (± 7 days) from inclusion until documented disease progression, withdrawal of consent, or death. Radiographic measurements must be performed to the RECIST specifications.

A Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer

A Phase II Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer

Best tumor response (defined as PR or CR in the first 6 months of treatment, assessed by investigators per RECIST v1.1 criteria).

Time to response is defined as the time from inclusion to the first objective tumor response and will be estimated using Kaplan-Meier method

Serious adverse events (SAEs)according to NCI CTCAE v5.0, by grade and their relationship to PLX038

Incidence of efficacy of PLX038 in pre-defined biomarker subgroups (BRCAness)

Maximum Plasma Concentration effect of PLX038

DoR is defined as the time from the first documented PR or CR until the date of disease progression or the date of death. DoR will be computed using Kaplan-Meier

PFS is defined as the time from inclusion to progression (per RECIST 1.1) or death, among included patients

PFS is defined as the time from inclusion to the first event among progression and death. OS is defined in the same way but only death is taken into account.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gemcitabine + Carboplatin in Breast Cancer	NCT00450762	Breast Cancer	gemcitabine carboplatin	18 Years - 75 Years	Ludwig-Maximilians - University of Munich
Capecitabine + Bendamustine in Women With Pretreated Locally Advanced or Metastatic Her2-negative Breast Cancer	NCT01891227	Breast Cancer	Capecitabine Bendamustine	18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie
DS-8201a for trEatment of aBc, BRain Mets, And Her2[+] Disease	NCT04420598	Advanced Breast... HER2-positive B... Brain Metastase... Leptomeningeal ...	Trastuzumab der...	18 Years -	MedSIR
Gemcitabine in Combination With Pemetrexed Long Term Infusion in the Treatment of Pretreated Metastatic Colorectal Cancer Patients	NCT01909830	Colorectal Canc...	Arm A : Gemcita...	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Bendamustine Combined With Alemtuzumab in Pretreated Chronic Lymphocytic Leukemia (CLL)	NCT00951457	Leukemia, Lymph...	Bendamustine Alemtuzumab	18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie
A Study on Tuvusertib (Oral ATR Inhibitor) in Combination With PLX038 (Topo1 Inhibitor) in Patients With Advanced Solid Tumors	NCT06337630	Solid Tumor	PLX038 + Tuvuse...	18 Years -	Institut Curie
Gemcitabine + Carboplatin in Breast Cancer	NCT00450762	Breast Cancer	gemcitabine carboplatin	18 Years - 75 Years	Ludwig-Maximilians - University of Munich
A Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer	NCT06162351	Breast Cancer	PLX038	18 Years -	Institut Curie
Bendamustine Combined With Alemtuzumab in Pretreated Chronic Lymphocytic Leukemia (CLL)	NCT00951457	Leukemia, Lymph...	Bendamustine Alemtuzumab	18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie
Gemcitabine in Combination With Pemetrexed Long Term Infusion in the Treatment of Pretreated Metastatic Colorectal Cancer Patients	NCT01909830	Colorectal Canc...	Arm A : Gemcita...	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Spots Global Cancer Trial Database for pretreated

Every month we try and update this database with for pretreated 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 pretreated

Every month we try and update this database with for pretreated 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 pretreated 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.