Clinical trial NCT04436120: Treatment Resistance Following Anti-cancer Therapies
Official title: TREATMENT RESISTANCE FOLLOWING ANTI-CANCER THERAPIES (TRANSLATE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Disease Progression
Keywords: Non Small Cell Lung Cancer
Renal Cell Carcinoma
HR+ HER2- Breast Cancer
Castrate-Resistant Prostate Cancer
Germline mutated BRCA, HER2- Breast Cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-06-17
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The TRANSLATE study aims to better understand why tumors become resistant to standard anti-cancer therapies.

New tumor biopsy and blood samples are collected after disease progression on standard-of-care anti-cancer treatment and compared to the initial (archival) tumor biopsy sample taken from the same patient.

Annotated reports of results from clinical Next Generation Sequencing (NGS) gene panel tests of both tumor and blood are sent directly from the testing lab to the study physician for discussion with the patient during the study.

Patients may participate in interventional treatment clinical trials at the same time as participating in the TRANSLATE study.

Primary data will be publicly available after the study to support further research.

Detailed description: Background: Development of new cancer treatments requires better understanding of why tumors develop resistance to standard-of-care (SOC) therapies. However, post-progression tumor biopsies are not routinely collected, limiting the tissue available to characterize mechanisms of treatment resistance. The TRANSLATE clinical study is specifically designed to address these critical gaps.

Trial design: TRANSLATE is a global, multicenter, translational study designed to collect and compare archival pre-treatment tumor tissue with paired de novo tumor and blood samples obtained following disease progression on SOC therapies, targeting therapeutically important areas of cancer biology.

Eligible Tumor Type and Most Recent SOC Therapy:

* Non-small-cell lung and Anti-PD-1/-L1 monotherapy
* Non-small-cell lung and Anti-PD-1/-L1 + platinum
* Clear cell renal cell carcinoma and Anti-PD-1/-L1 monotherapy
* Clear cell renal cell carcinoma and Doublet anti-PD-1/-L1 + anti-CTLA-4
* Clear cell renal cell carcinoma and Pembrolizumab + axitinib
* Clear cell renal cell carcinoma and Avelumab + axitinib
* HR+ HER2- breast and Palbociclib + hormonal therapy
* germline mutated BRCA breast and Olaparib or talazoparib monotherapy
* Castration-resistant prostate and Enzalutamide
* Castration-resistant prostate and Abiraterone + prednisone

Eligibility criteria include adults with locally advanced or metastatic tumors; radiographic evidence of progressive disease during the most recent SOC regimen; sufficient archival tumor tissue; and a post-progression tumor lesion that is safely accessible for a new biopsy.

The results from clinical NGS panel testing may help inform subsequent treatment plan or identification of relevant interventional clinical trials.

Patients are enrolled after disease progression on SOC and before change in treatment and participate in 3 study visits within approximately 3 months.

Next-generation sequencing results from analysis of tumor tissue and blood will be returned to the study physician and patient for review at a subsequent study visit within this timeframe.

The primary endpoint is the change in frequency of gene alterations between pre-treatment and post-progression tumor biopsies. Secondary endpoints address prioritized scientific hypotheses specific to each target area of biology and indication.

Primary data will be publicly available after the study to support further research.

Sponsored by Pfizer Inc.; EudraCT: 2018-003612-45.

Eligibility criteria: Inclusion Criteria:

* Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors treated as follows:
* Non small cell lung carcinoma (NSCLC) monotherapy: Disease progression (PD) on 1st line monotherapy anti PD-1/ L1.
* NSCLC combination: PD on 1st line anti PD-1/ L1 plus standard doublet platinum containing regimen; or PD on 1st-line anti-PD-1/-L1 plus standard doublet platinum-containing regimen followed by continuation of single agent anti-PD-1/-L1).
* Renal cell carcinoma (RCC) with clear cell component: PD on 2nd line monotherapy anti PD-1/ L1; or PD on 1st line combination of doublet anti-PD-1/ L1 with anti-CTLA-4; or PD on 1st-line combination of avelumab with axitinib or pembrolizumab with axitinib.
* HR+ HER2 adenocarcinoma of the breast: PD on 1st line combination of doublet palbociclib with hormonal therapy.
* Castrate resistant adenocarcinoma of the prostate: PD on enzalutamide monotherapy.
* Castrate resistant adenocarcinoma of the prostate: PD on abiraterone in combination with prednisone.
* germline mutated BRCA (gBRCAm), HER2- breast cancer: PD on a PARP inhibitor monotherapy in patients previously treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.
* Radiographic evidence of PD, including the target lesion being subjected to biopsy for the study, on the most recent regimen that requires a change in anti-cancer treatment.

Exclusion Criteria:

* Tumor biopsy taken from a bone or an irradiated target lesion.
* Discontinuation of current or most recent anti cancer therapy due to toxicity and not progressive disease.
* Initiation of new anti-cancer therapy after disease progression prior to planned biopsy.

Primary outcomes:
measure: Change in the Frequency of Gene Alterations Between Pre-treatment Tumor Samples (Archival) and Post-progression (De Novo) Tumor Biopsies
timeFrame: Through study completion, approximately 3 months
Secondary outcomes:
measure: Number of Participants With Fully Evaluable Archival and Post-Progression Tumor Biopsy by Cohort
timeFrame: Through study completion, approximately 3 months
measure: Overall Agreement Rate of Gene Alterations Between Post-Progression Tumor Biopsy and Blood NGS Results
timeFrame: Through study completion, approximately 3 months
measure: Change in Frequency of RB1 Gene Alterations Between Pre-Treatment Archival and Post-Progression Samples
timeFrame: Through study completion, approximately 3 months
measure: Percentage of Participants Who Carried the RB1 Gene Alterations in Post-Progression Blood cfDNA
timeFrame: Through study completion, approximately 3 months
measure: Change in Frequency of AR Gene Alterations Between Pre-Treatment Archival and Post-Progression Samples
timeFrame: Through study completion, approximately 3 months
measure: Percentage of Participants Who Carried the AR Gene Alterations in Post-Progression Blood cfDNA
timeFrame: Through study completion, approximately 3 months
measure: Change in Expression of Nuclear Hormone Receptors Between Pre-Treatment Archival and Post-Progression Samples
timeFrame: Through study completion, approximately 3 months
Other outcomes:
Locations:
city: Daphne
country: United States
facility: Southern Cancer Center, P.C.
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC
state: Alabama
city: Anchorage
country: United States
facility: Alaska Urological Institute dba Alaska Clinical Research Center
state: Alaska
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC-HOPE
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Glendale
country: United States
facility: The Oncology Institute of Hope Innovation
state: California
city: Long Beach
country: United States
facility: The Oncology Institute of Hope Innovation
state: California
city: Orange
country: United States
facility: UCI Medical Center-Chao Family Comprehensive Cancer Center
state: California
city: Santa Ana
country: United States
facility: The Oncology Institute of Hope Innovation
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Solvang
country: United States
facility: Sansum Clinic
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Whittier
country: United States
facility: ICRI-Administrative and Supplies Only
state: California
city: Pensacola
country: United States
facility: Woodlands Medical Specialists PA
state: Florida
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Viedma
country: Argentina
facility: Clínica Viedma S.A.
state: RIO Negro
city: Rosario
country: Argentina
facility: Sanatorio de la Mujer
state: Santa FÉ
city: Caba
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Ciudad Autónoma de Bs As
country: Argentina
facility: Centro de Educacion Medica e Investigaciones Clinicas"Norberto Quirno" CEMIC
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi - Site Notre Dame
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Gent
country: Belgium
facility: UZ Gent
city: Haine-Saint-Paul
country: Belgium
facility: Hôpital de Jolimont
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre Ottignies
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin
city: Colmar
country: France
facility: Hôpitaux Civils de Colmar, Centre Hospitalier Louis Pasteur
city: Créteil
country: France
facility: CHU Henri Mondor
city: Quint Fonsegrives
country: France
facility: Hôpital La Croix du Sud
city: Reims Cedex
country: France
facility: Institut Jean Godinot
city: Saint-Mande
country: France
facility: Hopital Bégin
city: Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: