Treatment Resistance Following Anti-cancer Therapies

Disease Progression Clinical Trial

Official title:

TREATMENT RESISTANCE FOLLOWING ANTI-CANCER THERAPIES (TRANSLATE)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04436120
• Other study ID #: A9001502
• Secondary ID: TRANSLATE2018-00
• Status: Terminated
• Phase: N/A
• Start date: February 13, 2019
• Est. completion date: December 14, 2020

Study information

• Verified date: May 2021
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: December 14, 2020
• Est. primary completion date: December 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Disease Progression

Intervention

Procedure:
• De novo tumor tissue biopsy
De novo tissue biopsy performed following disease progression
• Research blood draws
Blood biospecimens collected following disease progression

Locations

Country	Name	City	State
Argentina	Hospital Britanico de Buenos Aires	Caba
Argentina	Centro de Educacion Medica e Investigaciones Clinicas"Norberto Quirno" CEMIC	Ciudad Autónoma de Bs As
Argentina	Sanatorio de la Mujer	Rosario	Santa FÉ
Argentina	Clínica Viedma S.A.	Viedma	RIO Negro
Belgium	Grand Hôpital de Charleroi - Site Notre Dame	Charleroi
Belgium	AZ Maria Middelares	Gent
Belgium	UZ Gent	Gent
Belgium	Hôpital de Jolimont	Haine-Saint-Paul
Belgium	Clinique Saint-Pierre Ottignies	Ottignies
France	Centre Jean Perrin	Clermont Ferrand
France	Hôpitaux Civils de Colmar, Centre Hospitalier Louis Pasteur	Colmar
France	CHU Henri Mondor	Créteil
France	Hôpital La Croix du Sud	Quint Fonsegrives
France	Institut Jean Godinot	Reims Cedex
France	Hopital Bégin	Saint-Mande
United Kingdom	Royal Cornwall Hospital	Cornwall
United States	Alaska Urological Institute dba Alaska Clinical Research Center	Anchorage	Alaska
United States	Southern Cancer Center, P.C.	Daphne	Alabama
United States	The Oncology Institute of Hope Innovation	Glendale	California
United States	The Oncology Institute of Hope Innovation	Long Beach	California
United States	Southern Cancer Center, PC	Mobile	Alabama
United States	Southern Cancer Center, PC	Mobile	Alabama
United States	UCI Medical Center-Chao Family Comprehensive Cancer Center	Orange	California
United States	Woodlands Medical Specialists PA	Pensacola	Florida
United States	The Oncology Institute of Hope Innovation	Santa Ana	California
United States	Sansum Clinic	Santa Barbara	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Sansum Clinic	Solvang	California
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Arizona Oncology Associates, PC-HOPE	Tucson	Arizona
United States	ICRI-Administrative and Supplies Only	Whittier	California
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the frequency of gene alterations between pre treatment tumor samples and post progression tumor biopsies		Through study completion, approximately 3 months
Secondary	Proportion of patients with fully evaluable archival and post progression tumor biopsy (eg, sample sufficient for all intended analyses at all measured time points)		Through study completion, approximately 3 months
Secondary	Concordance of gene alterations between post progression biopsy tissue and blood NGS results		Through study completion, approximately 3 months
Secondary	Change in the frequency of alterations in genes encoding HLA, Beta-2 Microglobulin, STAT1, JAK1, JAK2, IFN-gamma and IFN- gamma R between pre treatment archival and post progression samples		Through study completion, approximately 3 months
Secondary	Frequency of alterations in genes encoding HLA, Beta 2 Microglobulin, STAT1, JAK1, JAK2, IFN-gamma and IFNGR in cfDNA		Through study completion, approximately 3 months
Secondary	Change in the frequency of RB1 gene alterations between pre treatment archival and post progression samples		Through study completion, approximately 3 months
Secondary	Frequency of RB1 gene alterations in cfDNA		Through study completion, approximately 3 months
Secondary	Change in the frequency of AR gene alterations between pre treatment archival and post progression samples		Through study completion, approximately 3 months
Secondary	Frequency of AR gene alterations in cfDNA		Through study completion, approximately 3 months
Secondary	Changes in the expression of nuclear hormone receptors or related RNA signatures reflecting nuclear receptor pathway activity between pre treatment archival and post progression samples		Through study completion, approximately 3 months
Secondary	Change in the frequency of somatic reversion alterations in gBRCA mutant allele between pre treatment archival and post progression samples		Through study completion, approximately 3 months

External Links

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