Ignite Creation Date:
2024-05-06 @ 3:10 AM
Last Modification Date:
2024-10-26 @ 11:29 AM
Study NCT ID:
NCT02229656
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-11-07
First Post:
2014-08-28
Brief Title:
Olaparib and Radiotherapy in Head and Neck Cancer
Sponsor:
The Netherlands Cancer Institute
Organization:
The Netherlands Cancer Institute
Study Overview
Official Title:
Olaparib Dose Escalation Trial in Patients Treated With Radiotherapy for Stage II-III Laryngeal and Stage II-III HPV-negative Oropharyngeal Squamous Cell Carcinoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Accelerated normofractionated radiotherapy is the treatment of choice in stage II-III laryngeal and oropharyngeal squamous cell carcinoma SCC However twenty to thirty percent of patients with stage II-III laryngeal and HPV negative oropharyngeal SCC develop disease progression mainly due to lack of locoregional control Radiosensitizers such as cisplatin and cetuximab are added to radiotherapy in more advanced stage of head and neck HN cancer These radiosensitizers improve loco-regional control and overall survival Unfortunately as these radiosensitizers notably cisplatin also dose intensify the radiation dose in normal tissues they also significantly increase toxicity Adding a more tumor-specific radiosensitizing agent could improve loco-regional control and overall survival without significantly increasing toxicity
Radiotherapy kills tumor cells by inducing DNA damage The efficacy of radiotherapy is limited by the ability of tumor cells to repair this DNA damage PolyADP-ribosepolymerase PARP is an essential enzyme in base excision repair and single strand break DNA repair DNA lesions arising from radiation treatment PARP inhibition and consequently the inhibition of PARP-facilitated DNA repair enhances the anti-tumor activity of radiotherapy as shown in preclinical studies including head and neck xenograft studies This radiosensitization is thought to be proliferation dependent and is more pronounced in homologous recombination HR deficient cells providing an opportunity for tumor specific targeting Genetic analyses suggest that HR deficiency is commonly found in HN SCC ATM loss has been reported in 60 of human HN SCC biopsies and FANC-F defects were reported in 15-21 of human HN SCC biopsies and cell lines
The efficacy of radiotherapy is also limited by tumor hypoxia as tumor hypoxia results in radioresistance Some PARP inhibiting compounds increase tumor perfusion in xenograft models thereby reducing hypoxia and specifically sensitizing tumor cells to radiotherapy Hypoxia is commonly found in HN SCC and a high pre-treatment hypoxic fraction in HN SCC tumors is associated with worse outcome The high prevalence of both hypoxia and HR deficiencies in HN SCC support the concept of tumor-specific radiosensitization by PARP inhibition in head and neck cancer patients
Olaparib is a potent PARP inhibitor developed as an anti-cancer drug for HR defected tumors and as a dose intensifier for chemo- and radiotherapy In humans olaparib has a low toxicity profile as a single agent with increasing bone marrow toxicity when combined with chemotherapy The combination of olaparib and radiotherapy for HN SCC is expected to improve locoregional control and thereby overall survival However this combination treatment has never been tested in humans before The purpose of this study is to determine the safety and tolerability of radiotherapy for stage II-III laryngeal and stage II-III HPV-negative oropharyngeal SCC with concurrent olaparib
Radiotherapy kills tumor cells by inducing DNA damage The efficacy of radiotherapy is limited by the ability of tumor cells to repair this DNA damage PolyADP-ribosepolymerase PARP is an essential enzyme in base excision repair and single strand break DNA repair DNA lesions arising from radiation treatment PARP inhibition and consequently the inhibition of PARP-facilitated DNA repair enhances the anti-tumor activity of radiotherapy as shown in preclinical studies including head and neck xenograft studies This radiosensitization is thought to be proliferation dependent and is more pronounced in homologous recombination HR deficient cells providing an opportunity for tumor specific targeting Genetic analyses suggest that HR deficiency is commonly found in HN SCC ATM loss has been reported in 60 of human HN SCC biopsies and FANC-F defects were reported in 15-21 of human HN SCC biopsies and cell lines
The efficacy of radiotherapy is also limited by tumor hypoxia as tumor hypoxia results in radioresistance Some PARP inhibiting compounds increase tumor perfusion in xenograft models thereby reducing hypoxia and specifically sensitizing tumor cells to radiotherapy Hypoxia is commonly found in HN SCC and a high pre-treatment hypoxic fraction in HN SCC tumors is associated with worse outcome The high prevalence of both hypoxia and HR deficiencies in HN SCC support the concept of tumor-specific radiosensitization by PARP inhibition in head and neck cancer patients
Olaparib is a potent PARP inhibitor developed as an anti-cancer drug for HR defected tumors and as a dose intensifier for chemo- and radiotherapy In humans olaparib has a low toxicity profile as a single agent with increasing bone marrow toxicity when combined with chemotherapy The combination of olaparib and radiotherapy for HN SCC is expected to improve locoregional control and thereby overall survival However this combination treatment has never been tested in humans before The purpose of this study is to determine the safety and tolerability of radiotherapy for stage II-III laryngeal and stage II-III HPV-negative oropharyngeal SCC with concurrent olaparib
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2011-002963-79 | EUDRACT_NUMBER | None | None |