Survival Prolongation by Rationale Innovative Genomics

Phase 1

Terminated

• Conditions: Non-small Cell Lung Cancer Metastatic; Non-small Cell Lung Cancer Stage IIIB
• Interventions: Drug: Avelumab; Drug: Axitinib; Drug: Palbociclib

• Registration Number: NCT03386929
• Lead Sponsor: Worldwide Innovative Network Association

Brief 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.

Study Timeline

• Study Start: 2017-11-29
• Study First Submitted: 2017-12-14
• Study First Submitted QC: 2017-12-20
• Study First Posted: 2017-12-29
• Primary Completion: 2022-12-29
• Study Completion: 2022-12-29
• Results First Submitted: 2023-10-20
• Status Verified: 2023-11
• Results First Submitted QC: 2023-11-29
• Last Update Submitted: 2023-11-29
• Results First Posted: 2023-12-18
• Last Update Posted: 2023-12-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Avelumab, Axitinib, Palbociclib	Avelumab	For the Phase 1: Avelumab is administered intravenously (IV) on Day 1 and Day 15 of a 28 day cycle in combination with axitinib po bid (every day of a 28 day cycle) and palbociclib po (on days 8-28 of a 28 day cycle). For the Phase 2: Avelumab, axitinib and palbociclib are administered at the recommended phase 2 dose (RP2D) as determined during the phase 1 part of the study.
Avelumab, Axitinib, Palbociclib	Palbociclib	For the Phase 1: Avelumab is administered intravenously (IV) on Day 1 and Day 15 of a 28 day cycle in combination with axitinib po bid (every day of a 28 day cycle) and palbociclib po (on days 8-28 of a 28 day cycle). For the Phase 2: Avelumab, axitinib and palbociclib are administered at the recommended phase 2 dose (RP2D) as determined during the phase 1 part of the study.
Avelumab, Axitinib, Palbociclib	Axitinib	For the Phase 1: Avelumab is administered intravenously (IV) on Day 1 and Day 15 of a 28 day cycle in combination with axitinib po bid (every day of a 28 day cycle) and palbociclib po (on days 8-28 of a 28 day cycle). For the Phase 2: Avelumab, axitinib and palbociclib are administered at the recommended phase 2 dose (RP2D) as determined during the phase 1 part of the study.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	Baseline up to approximately 24 months	Progression Free Survival (PFS) is defined as the time from the first dose of study treatment to the date of disease progression by RECIST 1.1 or death due to any cause, whichever occurs first.
Duration of the Response	Baseline up to approximately 24 months	Duration of Response (DR) is defined for patients with confirmed objective response (Complete Response \[CR\] or Partial Response \[PR\]) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
Overall Survival (OS)	Baseline up to approximately 24 months	OS is defined as the time from the first dose of study treatment to the date of death due to any cause.
Incidence of the Tested 3-Drug Combination Therapy-Emergent Adverse Events and Serious Adverse Events	From informed consent signature through 90 days after administration of the treatment (last dose)	The occurrence of adverse events and serious adverse events reported from the signing of an informed consent through 90 days after the last administration of the treatment will be summarized for all subjects who received at least one dose of the study treatment (safety population) and will be evaluated based on NCI CTCAE v4.03: June 14, 2010.
Response Rate (RR)	Baseline up to approximately 24 months	Response rate is defined as the proportion of participants with reduction in tumor burden of a predefined amount based on RECIST 1.1 evaluation
SIMS Algorithm to Predict Clinical Outcome	4 years	The proportion of participants whose SIMS analysis matches the treatment combination, will be correlated retrospectively to clinical outcome.

Secondary Outcome Measures

Name	Time	Method
Genomic and Transcriptomic Profile	4 years	Genomic (DNA) and transcriptomic (RNA) aberrations (mutations, translocations, rearrangements and changes in expression level) identified in the study population (Non-Small Cell Lung) will be described.
Incidence of Treatment-related and or Biopsy-related Serious Adverse Events	4 years	The occurrence of treatment-related and or biopsy-related serious adverse events as assessed by NCI CTCAE v4.03 will be summarized for all study subjects.

Trial Locations

Locations (5)

Avera Cancer Center; 🇺🇸 Sioux Falls, South Dakota, United States

Centre Hospitalier Luxembourg; 🇱🇺 Luxembourg, Luxembourg

Chaim Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

UCSD Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Vall Hebron Institute of Oncology; 🇪🇸 Barcelona, Spain