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Survival Prolongation by Rationale Innovative Genomics | Clinical Trials | Clareo Health

TERMINATEDPHASE1/PHASE2

Survival Prolongation by Rationale Innovative Genomics

A Proof of Concept Study to Explore Safety and Efficacy of Tri-therapy Approach in Advanced/Metastatic NSCLC and Retrospectively Assess the Ability of Integrated Genomics and Transcriptomics to Match Patients to the Combination

NCT03386929•Worldwide Innovative Network Association

View on ClinicalTrials.gov

Summary

Patients with advanced/metastatic non-small cell lung cancer (NSCLC) with no documented targetable alterations (Epidermal Growth Factor Receptor (EGFR) mutation, Anaplastic Lymphoma Kinase (ALK) translocation, ROS1 mutation if available or MET exon 14 skipping mutation if available) will receive a tri-therapy associating avelumab, axitinib and palbociclib.

Detailed Description

During the Phase 1 (approximately 30 patients), the tri-therapy will be tested at different doses following a specific dose-escalation scheme (3 + 3 model) in order to establish the safety and identify the Maximum Tolerated Dose (MTD) and recommended dose for the Phase 2 (RP2D). The phase 2 will confirm the safety and will assess the clinical utility of the tri-therapy approach in the treatment of advanced/metastatic NSCLC (100 patients). The study will also explore the clinical utility of the Simplified Interventional Mapping System (SIMS), a new tool/algorithm enabling matching of NSCLC patients with combination therapy. For this purpose tumor/metastasis and matched normal tissue biopsies will be requested in order to obtain sequencing and expression profiles.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•ELIGIBILITY CRITERIA
•Age: Men and women aged \>18 years,
•Signed written informed consent,
•Any histologic type of locally advanced or metastatic NSCLC,
•Life expectancy of ≥ 12 weeks,
•Measurable or evaluable (cytologically or radiologically detectable disease such as ascites, peritoneal deposits, or lesions which do not fulfill RECIST 1.1 criteria for measurable disease) lesions according to RECIST 1.1 criteria for phase 1 portion. For phase 2, all patients must have RECIST 1.1 measurable disease,
•Physiologic function:
•* Hematologic: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused),
•* Hepatic: Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN,
•* Renal: Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
+23 more criteria

Exclusion Criteria

•Patients with documented oncogenic aberrations at enrollment: EGFR, ALK, ROS1 when available, MET exon 14 skipping when available. For squamous undifferentiated cell carcinoma, documentation of these aberrations is not mandatory. Note: For Phase 1 portion, all patients with adenocarcinoma histology must have documentation of results for druggable oncogenic aberrations (EGFR mutations, ALK rearrangements, and ROS1 when available) prior to enrollment on the study.
•For Phase 1 portion, \>2 lines of prior therapy in the metastatic setting.
•For the dose escalation phase of the study or until the MTD for the combination regimen has been determined, patients with moderate hepatic impairment defined as AST, ALT, alkaline phosphatase (ALP) \>5 times ULN, which would be grade 3 or higher. However, patients with liver metastases with AST/ALT ≤ 5 x ULN can be included in the study.
•For Phase 2 portion, any prior therapy in the metastatic setting.
•Clinical criteria for phase 1 and phase 2 studies:
•Patients with treated brain metastases are eligible as are patients with new, active untreated brain metastasis.
•Participants with a history of myocardial infarction within the last 2 years or with significant cardiac arrhythmias uncontrolled by medication or pacemaker,
•Participants with any history of interstitial lung disease,
•Prior clinically significant toxicities from anticancer agents or radiotherapy which have not regressed to Grade ≤ 1 severity (NCI-CTCAE version 4.03) apart from peripheral neuropathy and alopecia,
•* IMMUNOSUPRESSANTS: Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
+10 more criteria

Locations (5)

UCSD Moores Cancer Center

La Jolla, California, United States

Avera Cancer Center

Sioux Falls, South Dakota, United States

Chaim Sheba Medical Center

Ramat Gan, Israel

Centre Hospitalier Luxembourg

Luxembourg, Luxembourg

Vall Hebron Institute of Oncology

Barcelona, Spain

Key Dates

Start Date

November 29, 2017

Primary Completion Date

December 29, 2022

Completion Date

December 29, 2022

Last Updated

December 18, 2023

Enrollment

ACTUAL participants

Conditions

Non-small Cell Lung Cancer MetastaticNon-small Cell Lung Cancer Stage IIIB

Interventions

Avelumab

DRUG

Axitinib

DRUG

Palbociclib

DRUG

Risk-adapted, Proteomic-guided Systemic Therapy for Previously Untreated Advanced Non-small Cell Lung Cancer

NCT07250477

Non-small Cell Lung Cancer Stage IIICNon-small Cell Lung Cancer Stage IV+3 more

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RECRUITINGPHASE1/PHASE2

AK129 Combination Therapy for Advanced Solid Tumors

NCT06943820

Non-small Cell Lung Cancer Stage IIIB/IVHead and Neck Squamous Cell Carcinoma (HNSCC)+2 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: December 18, 2023Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Survival Prolongation by Rationale Innovative Genomics

Inclusion Criteria

Exclusion Criteria

Risk-adapted, Proteomic-guided Systemic Therapy for Previously Untreated Advanced Non-small Cell Lung Cancer

AK129 Combination Therapy for Advanced Solid Tumors

Alectinib Pharmacokinetic in Patients With NSCLC

Befotertinib and Icotinib for NSCLC With Uncommon EGFR Mutations

An Exploratory Study of Atezolizumab and Bevacizumab in Hepatocellular Carcinoma and Non-Small Cell Lung Cancer With Liver Metastases (INTEGRATE)

Staggered, Chemo-Immunotherapy With Durvalumab, MEDI4736 Pemetrexed & Carboplatin (PC) for Metastatic Non-Squamous NSCLC