Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Uterine Cervical Neoplasms

Carcinoma

Colorectal Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

5 mg/kg to 15 mg/kg in combination with chemotherapy.

Bevacizumab Biosimilar MB02

Livan Delgado-Roche, Ph.D.

Sashka Dunkerley Mora, M.D., M.Sc.

David Suárez García, M.D.

Eliseo Neftalí de la Cruz Escobar, M.D.

Alberto Alfonso Pimentel Rentería, M.D.

David Francisco Cantú de León, M.D., Ph.D.

José Gustavo Núñez Cerrillo, M.D.

This is a post-marketing observational study aimed to evaluated the safety profile of Effivia®, a biosimilar of bevacizumab, in mexican patients with different types of cancer.

Safety of Effivia®, a Bevacizumab Biosimilar

Post-marketing Safety of Effivia®, a Bevacizumab Biosimilar: Phase IV, Observational, Multicenter Clinical Study in Mexican Population

Frequency and characteristics of adverse events (serious and non serious)

Servicios Especializados en Ensayos Clínicos, S.C.

Laboratorios Liomont

Rare Diseases

Adenocarcinoma

Adenocarcinoma of Lung

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Lung Adenocarcinoma

Pembrolizumab

Carboplatin

Pemetrexed

Mirdametinib 4 mg twice/day for 7 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab.

Pemetrexed/pembrolizumab until progression Number of participants : 3 to 6 patients

Mirdametinib 4 mg twice/day for 14 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab.

Pemetrexed/pembrolizumab until progression Number of participants : 3 to 6 patients

Mirdametinib 6 mg twice/day for 7 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab.

Pemetrexed/pembrolizumab until progression Number of participants : 3 to 6 patients

Mirdametinib 6 mg twice/day for 14 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab.

Pemetrexed/pembrolizumab until progression Number of participants : 3 to 6 patients

Carboplatin / Pemetrexed / Pembrolizumab for the first 4 cycles

Carboplatin / Pemetrexed / Pembrolizumab + mirdametinib for the first 4 cycles

Mirdametinib 4 mg twice/day for 7 days per cycle

Phase I - Mirdametinib - Level 1

For phase 2 : Randomisation with 2 arm : Standard arm and experimental arm

Phase II - Mirdametinib

Mirdametinib 4 mg twice/day for 14 days per cycle

Phase I - Mirdametinib - Level 2

Mirdametinib 6 mg twice/day for 7 days per cycle

Phase I - Mirdametinib - Level 3

Mirdametinib 6 mg twice/day for 14 days per cycle

Phase I - Mirdametinib - Level 4

François FG GHIRINGHELLI, Professor

Emilie ER REDERSTORFF, Project manager

Monocentric study composed by 2 steps :

1. First step is a phase I with the aim of establish the recommended dose of mirdametinib administration (2 or 4 mg twice a day for 7 or 14 days per cycle for the 4 first of carboplatin/pemetrexed/pembrolizumab treatment)
2. Second step is a non comparative randomized (2:1) phase II trial testing the recommended dose of mirdametinib administration. The aim is the efficacy and safety of short course of mirdametinib treatment for the 4 first cycles of the carboplatin/pemetrexed/pembrolizumab treatment.

1) Phase I (15-24 patients) Using a classical "3+3 design": The phase I will included a maximum 24 patients. 3 patients will be included in dose level 1, if not DLT occurs 3 patients will be included in level 2. If 1 DLT occurs 3 additional patients will be included; if 2 or more DLT occurs the trial will be stopped. At level 2 if no DLT occurs RP2D 3 patients will be included at level 3; If 1 DLT occurs 3 additional patients will be included; if 2 or more DLT occurs RP2D will be level 1. Similar rules will be applied for level 3 and 4. In absence of DLT CXCL10 and PD-L1, CD8 immune infiltrates and immunoscore IC (CD8-PDL1 dual markers) at baseline and 6 weeks, and clinical efficacy will be presented to IDMC for definition of RP2D. At the end of phase I inclusion toxicity, efficacy data and biological data (CXCL10 seric and IHC expression and PD-L1, CD8 immune infiltrates and immunoscore IC (CD8-PDL1 dual markers) at baseline and 6 weeks, PK and PK/PD data will be presented to IDMC to validate RP2D.

* 3 +/- 3 patients for level 1 (mirdametinib 4 mg twice/ 7 days)
* 3 +/- 3 patients for level 2 (mirdametinib 4 mg twice/ 14 days)
* 3 +/- 3 patients for level 3 (mirdametinib 6 mg twice/ 7 days)
* 3 +/- 3 patients for level 4 (mirdametinib 6 mg twice/ 14 days)

PHASE II (78 patients) Sample size calculation was performed using PASS v13. In keynote 189 response rate in PD-L1 \<50% was 40% (28). A 3-month overall response rate (ORR) of 40% is considered unacceptable (P0=40%). The study team expect an ORR of 55% in the experiment arm (P1=55%, acceptable ORR).

Using a single stage design (A Hern, exact test) with unilateral α=10%, power=80%, 50 patients are needed for the primary endpoint analysis in the experimental arm. With 5% of non-evaluable patients, 52 patients will be included in this arm. With a 2:1 randomization the control arm will include 26 patients. A total of 78 subjects are then needed in the phase 2 part.

Phase 1 (escalation dose)

* Level 1: mirdametinib 4 mg twice/day for 7 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab until progression (3-6 patients)
* Level 2: mirdametinib 4 mg twice/day for 14 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab until progression (3-6 patients)
* Level 3: mirdametinib 6 mg twice/day for 7 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab until progression (3-6 patients)
* Level 4: mirdametinib 6 mg twice/day for 14 days per cycle for the 4 first cycles + carboplatin/pemetrexed/pembrolizumab until progression (3-6 patients)

Phase 2 (randomized)

* Standard arm : Carboplatin/pemetrexed/pembrolizumab for the first 4 cycles until progression (26 patients)
* Experimental arm : Carboplatin/pemetrexed/pembrolizumab + mirdametinib for the first 4 cycles until progression (52 patients)

Clinical Trial Evaluating the Safety and Efficacy of Chemoimmunotherapy Plus Short Course of Mek Inhibitor in First Line of Treatment of Metastatic Non Squamous Non Small Cell Lung Adenocarcinoma With PDL1 < 50 %.

Phase Ib/II Clinical Trial Evaluating the Safety and Efficacy of Chemoimmunotherapy Plus Short Course of Mek Inhibitor in First Line of Treatment of Metastatic Non Squamous Non Small Cell Lung Adenocarcinoma With PDL1 < 50 %.

DLT is defined as any of the following toxicities occurring during the first 21 days after administration of the first dose. Adverse events (AEs) will be defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Centre Georges Francois Leclerc

Symptoms and General Pathology

Recurrence

Three loading doses of OGX-427 at 600mg intravenously (IV) will be administered over 9 days. Following the loading dose period, OGX-427 will be administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle during the Treatment Phase. The Treatment Phase will be followed by a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle.

Three loading doses of placebo will be administered intravenously (IV) over 9 days. Following the loading dose period, placebo will be administered IV weekly Days 1, 8 and 15 of each 21 day cycle during the Treatment Phase. The Treatment Phase will be followed by a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle.

Three loading doses of 600mg OGX-427 will be administered intravenously (IV) during a 9 day period. Then 600mg IV OGX-427 will be given weekly on Days 1, 8 and 15 of each 21 day cycle prior to the administration of pemetrexed (500mg/m\^2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle for a maximum of four treatment cycles. Patients who respond to treatment or have stable disease will continue to receive 600 mg IV OGX-427 plus 500mg/m2 IV pemetrexed weekly until toxicity or disease progression.

OGX-427

Three loading doses of placebo will be administered intravenously (IV) during a 9 day period. Then placebo (IV) will be given weekly on Days 1, 8 and 15 of each 21 day cycle prior to the administration of pemetrexed (500mg/m\^2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle for a maximum of four treatment cycles. Patients who respond to treatment or have stable disease will continue to receive placebo (IV) plus 500mg/m2 IV pemetrexed weekly until toxicity or disease progression.

Placebo

David R. Spigel, M.D.

This randomized phase II study will compare the efficacy and safety of the combination of carboplatin and pemetrexed with and without OGX-427 in patients with previously untreated advanced non-squamous NSCLC.

Modern doublet chemotherapy improves survival in patients with advanced non-small cell lung cancer (NSCLC) compared with supportive care alone, with non-squamous NSCLC patients treated with platinum/pemetrexed living longer than patients treated with platinum/gemcitabine. Despite these advances, poor outcomes with advanced disease warrant exploration of novel drugs with unique mechanisms of action. Preclinical evidence in lung cancer models shows promising antitumor activity with OGX-427 in combination with platinum based therapy or pemetrexed. In this double-blind, placebo-controlled, Phase II study, pemetrexed and carboplatin plus OGX-427 followed by maintenance pemetrexed and OGX-427 will be compared with pemetrexed and carboplatin plus placebo followed by maintenance pemetrexed and placebo in patients with previously untreated advanced non-squamous NSCLC.

Phase II Trial of Carboplatin and Pemetrexed +/- OGX-427 in Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer

Double-Blind Randomized Phase II Trial of Carboplatin and Pemetrexed With or Without OGX-427 in Patients With Previously Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer (The Spruce Clinical Trial)

Defined as the time (in months) from date of randomization to the date of first observation of progression based on radiological assessment by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, or date of death from any cause, in the absence of progressive disease (PD) or censored at the date of last adequate tumor assessment. Progressive Disease is defined by RECIST v1.1 as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest (nadir) sum while on study (this includes the baseline sum if that is the smallest on study), or the appearance of one or more new lesions.

Defined as the number of patients with objective evidence of complete or partial response (CR or PR) using RECIST v 1.1. A CR is the complete disappearance of all target lesions. A PR is a decrease in baseline of 30% or more of the diameter(s) of all target lesions.

Defined as the time (in months) from date of randomization to date of death from any cause, or censored at the date last known alive.

A treatment-related adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events were evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

Achieve Life Sciences

SCRI Development Innovations, LLC

Any untoward medical occurrence in a participant regardless of the relationship with the study drug per the Investigator's assessment. Adverse events were evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. All-Cause Mortality was assessed in all randomized participants, while Serious and Other (Not Including Serious) Adverse Events was only assessed in participants who received at least one dose of study treatment.

OGX-427: Three loading doses of OGX-427 at 600mg IV will be administered Days -9 to -1.

Following the loading dose period, OGX-427 will be administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle during the Treatment Phase. OGX-427 will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered.

Patients with objective response or stable disease after four cycles of therapy will move on to a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression.

Placebo: Three loading doses of placebo will be administered IV Days -9 to -1.

Following the loading dose period, placebo will be administered IV weekly Days 1, 8 and 15 of each 21 day cycle during the Treatment Phase. Placebo will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered.

Patients with objective response or stable disease after four cycles of therapy will move on to a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression.

OGX-427: Three loading doses of OGX-427 at 600mg intravenously (IV) will be administered over 9 days.

Following the loading dose period, OGX-427 will be administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle. OGX-427 will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered.

Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression.

Placebo: Three loading doses of placebo will be administered intravenously (IV) over 9 days.

Following the loading dose period, placebo will be administered IV weekly Days 1, 8 and 15 of each 21 day cycle. Placebo will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered.

Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Patients that were randomized to either OGX-427 or placebo

Senior Director, Regulatory Science

Median Progression-Free Survival

Number of OGX-427 Versus Placebo Participants With an Objective Response

Median Overall Survival

Randomized patients who received at least one dose of study treatment.

Number of Patients With a Treatment-Related Adverse Event as a Measure of Safety.

Overall Study

Disease Progression

Subjects will take Pazopanib, 800 mg daily by mouth throughout the time in study

Pazopanib, 800 mg by mouth daily each 21 day cycle

Pazopanib

Thomas Stinchcombe, MD

This is an open label Phase II Trial that using the investigational anti-cancer agent, Pazopanib to see whether non-squamous non-small cell lung cancer will respond to its use by decreasing the size of the tumor or stopping its growth.

This multi-centered phase II trial will examine pazopanib stage IIIB/IV non-squamous NSCLC patients who have progressed on first-line therapy containing bevacizumab. Treatment should continue until disease progression, unacceptable toxicity, study withdrawal, or death. Patients who progress will be treated at the discretion of their physician. all patients who initiate treatment will be evaluated for disease control rate, which is the primary endpoint of this study.

The primary objective is to estimate the disease control rate of pazopanib alone in patients with stage IIIB/IV non-squamous NSCLC who progressed while on bevacizumab. Disease control rate id defined as complete (CR) + partial response (PR) + stable disease (SD) lasting greater than or equal to 12 weeks as defined by RECIST.

Secondary Objectives To estimate the combined response rate (CR + PR) of pazopanib according to RECIST To estimate the progression free survival (defined as time of enrollment until disease progression or death) and overall survival (defined as time of enrollment until death) of patients treated with pazopanib.

To evaluate the safety and tolerability of pazopanib using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0 To explore potential correlations between blood biomarkers and clinical response.

Pazopanib is dosed continuously throughout the study. Cycle lengths are identified as 21 days for purposes of the calendar.

The treatment dosage and administration for participating subjects will be, Pazopanib, 800 mg by mouth daily during a 21 day cycle until disease progression.

Pazopanib In Stage IIIB/IV NSCLC Lung Cancer After Progression on First Line Therapy Containing Bevacizumab

A Multi-Center Open Label Phase II Study of Pazopanib in Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer After Progression on First Line Therapy Containing Bevacizumab

Response (CR + PR + SD) as defined by RECIST v1.1 lasting equal to or greater than 12 weeks in patients treated with pazopanib alone for stage IIIB/IV non-squamous NSCLC after progression on first line therapy containing bevacizumab Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Complete Response (CR) is defined as Disappearance of all target lesions; Partial Response (PR), as a \>=30% decrease in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions; Progression, as a 20% increase in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. Target lesions are representative of all involved organs and measurable by radiographic imaging.

Estimate of combined response rate (Complete Response (CR) + Partial Response (PR) per RECIST v1.1 Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Complete Response (CR) is defined as the disappearance of all target lesions and Partial Response (PR) as a \>=30% decrease in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions.Target lesions are representative of all involved organs and measurable by radiographic imaging.

Progression free survival is defined as time of enrollment until disease progression or death Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Progression is defined as a 20% increase in the sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) of all target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Target lesions are representative of all involved organs and measurable by radiographic imaging.

Overall survival is defined as the time of enrollment until death

GlaxoSmithKline

UNC Lineberger Comprehensive Cancer Center

Subjects will take Pazopanib, 800 mg daily by mouth throughout the time in study

Pazopanib: Pazopanib, 800 mg by mouth daily each 21 day cycle

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety of Effivia®, a Bevacizumab Biosimilar	NCT06313268	Metastatic Colo... Metastatic Cerv... Non Squamous No...	Bevacizumab Bio...	18 Years -	Laboratorios Liomont
Clinical Trial Evaluating the Safety and Efficacy of Chemoimmunotherapy Plus Short Course of Mek Inhibitor in First Line of Treatment of Metastatic Non Squamous Non Small Cell Lung Adenocarcinoma With PDL1 < 50 %.	NCT05937906	Non-Small Cell ...	Phase I - Mirda... Phase II - Mird... Phase I - Mirda... Phase I - Mirda... Phase I - Mirda...	18 Years -	Centre Georges Francois Leclerc
Phase II Trial of Carboplatin and Pemetrexed +/- OGX-427 in Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer	NCT01829113	Non Squamous No...	OGX-427 Placebo	18 Years -	SCRI Development Innovations, LLC
Clinical Trial Evaluating the Safety and Efficacy of Chemoimmunotherapy Plus Short Course of Mek Inhibitor in First Line of Treatment of Metastatic Non Squamous Non Small Cell Lung Adenocarcinoma With PDL1 < 50 %.	NCT05937906	Non-Small Cell ...	Phase I - Mirda... Phase II - Mird... Phase I - Mirda... Phase I - Mirda... Phase I - Mirda...	18 Years -	Centre Georges Francois Leclerc
Safety of Effivia®, a Bevacizumab Biosimilar	NCT06313268	Metastatic Colo... Metastatic Cerv... Non Squamous No...	Bevacizumab Bio...	18 Years -	Laboratorios Liomont
Safety of Effivia®, a Bevacizumab Biosimilar	NCT06313268	Metastatic Colo... Metastatic Cerv... Non Squamous No...	Bevacizumab Bio...	18 Years -	Laboratorios Liomont
Phase II Trial of Carboplatin and Pemetrexed +/- OGX-427 in Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer	NCT01829113	Non Squamous No...	OGX-427 Placebo	18 Years -	SCRI Development Innovations, LLC
Pazopanib In Stage IIIB/IV NSCLC Lung Cancer After Progression on First Line Therapy Containing Bevacizumab	NCT01262820	Lung Cancer	Pazopanib	18 Years -	UNC Lineberger Comprehensive Cancer Center

Spots Global Cancer Trial Database for non squamous non small cell lung cancer