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Treatment Resistance Following Anti-cancer Therapies

Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT04436120
Collaborator
(none)
38
Enrollment
33
Locations
1
Arm
22
Actual Duration (Months)
1.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Procedure: De novo tumor tissue biopsy
  • Procedure: Research blood draws
 N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
38 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
TREATMENT RESISTANCE FOLLOWING ANTI-CANCER THERAPIES (TRANSLATE)
Actual Study Start Date :
Feb 13, 2019
Actual Primary Completion Date :
Dec 14, 2020
Actual Study Completion Date :
Dec 14, 2020

Arms and Interventions

Arm Intervention/Treatment
Other: Tumor biopsy and blood draw

Tumor biopsy and blood draw

Procedure: De novo tumor tissue biopsy
De novo tissue biopsy performed following disease progression

Procedure: Research blood draws
Blood biospecimens collected following disease progression

Outcome Measures

Primary Outcome Measures

  1. Change in the frequency of gene alterations between pre treatment tumor samples and post progression tumor biopsies [Through study completion, approximately 3 months]

Secondary Outcome Measures

  1. 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]

  2. Concordance of gene alterations between post progression biopsy tissue and blood NGS results [Through study completion, approximately 3 months]

  3. 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]

  4. 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]

  5. Change in the frequency of RB1 gene alterations between pre treatment archival and post progression samples [Through study completion, approximately 3 months]

  6. Frequency of RB1 gene alterations in cfDNA [Through study completion, approximately 3 months]

  7. Change in the frequency of AR gene alterations between pre treatment archival and post progression samples [Through study completion, approximately 3 months]

  8. Frequency of AR gene alterations in cfDNA [Through study completion, approximately 3 months]

  9. 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]

  10. 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Southern Cancer Center, P.C. Daphne Alabama United States 36526
2 Southern Cancer Center, PC Mobile Alabama United States 36607
3 Southern Cancer Center, PC Mobile Alabama United States 36608
4 Alaska Urological Institute dba Alaska Clinical Research Center Anchorage Alaska United States 99503
5 Arizona Oncology Associates, PC-HOPE Tucson Arizona United States 85704
6 Arizona Oncology Associates, PC - HOPE Tucson Arizona United States 85711
7 The Oncology Institute of Hope Innovation Glendale California United States 91204
8 The Oncology Institute of Hope Innovation Long Beach California United States 90805
9 UCI Medical Center-Chao Family Comprehensive Cancer Center Orange California United States 92868-3201
10 The Oncology Institute of Hope Innovation Santa Ana California United States 92705
11 Sansum Clinic Santa Barbara California United States 93105
12 Sansum Clinic Solvang California United States 93463
13 The Oncology Institute of Hope and Innovation Whittier California United States 90602
14 ICRI-Administrative and Supplies Only Whittier California United States 90603
15 Woodlands Medical Specialists PA Pensacola Florida United States 32503
16 Seattle Cancer Care Alliance Seattle Washington United States 98109
17 University of Washington Medical Center Seattle Washington United States 98195
18 Clínica Viedma S.A. Viedma RIO Negro Argentina 8500
19 Sanatorio de la Mujer Rosario Santa FÉ Argentina S2000ORE
20 Hospital Britanico de Buenos Aires Caba Argentina C1280AEB
21 Centro de Educacion Medica e Investigaciones Clinicas"Norberto Quirno" CEMIC Ciudad Autónoma de Bs As Argentina C1431FWO
22 Grand Hôpital de Charleroi - Site Notre Dame Charleroi Belgium 6000
23 AZ Maria Middelares Gent Belgium 9000
24 UZ Gent Gent Belgium 9000
25 Hôpital de Jolimont Haine-Saint-Paul Belgium 7100
26 Clinique Saint-Pierre Ottignies Ottignies Belgium 1340
27 Centre Jean Perrin Clermont Ferrand France 63011
28 Hôpitaux Civils de Colmar, Centre Hospitalier Louis Pasteur Colmar France 68024
29 CHU Henri Mondor Créteil France 94010
30 Hôpital La Croix du Sud Quint Fonsegrives France 31130
31 Institut Jean Godinot Reims Cedex France 51056
32 Hopital Bégin Saint-Mande France 94160
33 Royal Cornwall Hospital Cornwall United Kingdom TR1 3IJ

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT04436120
Other Study ID Numbers:
  • A9001502
  • TRANSLATE
  • 2018-003612-45
First Posted:
Jun 17, 2020
Last Update Posted:
May 14, 2021
Last Verified:
May 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Pfizer
Non Small Cell Lung Cancer
Renal Cell Carcinoma
HR+ HER2- Breast Cancer
Castrate-Resistant Prostate Cancer
Germline mutated BRCA, HER2- Breast Cancer
Additional relevant MeSH terms:
Disease Progression

Study Results

No Results Posted as of May 14, 2021