Ignite Creation Date:
2025-12-24 @ 9:34 PM
Ignite Modification Date:
2025-12-29 @ 5:20 AM
Study NCT ID:
NCT00678132
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
2008-05-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
AZD2281 and Cisplatin Plus Gemcitabine to Treat Solid Tumor Cancers
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase I Combination Study of AZD2281 and Cisplatin Plus Gemcitabine in Adults With Solid Tumors
Status:
COMPLETED
Status Verified Date:
2012-09-07
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:
Background:
* AZD2281 is an experimental drug in a class of agents called PARP inhibitors. PARP is a protein that is involved in repairing DNA damage; PARP inhibitors interfere with that process.
* Cisplatin and gemcitabine are approved by the United States Food and Drug Administration to treat certain cancers.
Objectives:
* To determine the optimum doses of AZD2281, cisplatin and gemcitabine in combination that can safely be given to patients with solid tumor cancers.
* To evaluate the response of the tumor to the drug combination and determine the side effects of the treatment.
Eligibility:
-Patients 18 years or older with an advanced solid tumor cancer for whom standard treatments are not effective.
Design:
* In this dose escalation study, the first small group of patients receives the smallest study doses of the study drugs. Subsequent groups receive incrementally higher doses as long as the preceding group does not experience unacceptable side effects. When the highest safe dose is determined, additional patients entering the study receive that dose.
* Patients receive treatment in 21-day cycles as follows:
* Days 1-4: AZD2281 by mouth twice a day
* Day 3: gemcitabine thorough a vein over 1 hour; then cisplatin through a vein over 1 hour.
* Day 10: gemcitabine through a vein over 1 hour.
* Evaluations during treatment include the following:
* Physical examination, vital signs check and blood tests every 3 weeks.
* CT scans every 6 weeks to evaluate the tumor.
* Treatment may continue until it is no longer beneficial.
* AZD2281 is an experimental drug in a class of agents called PARP inhibitors. PARP is a protein that is involved in repairing DNA damage; PARP inhibitors interfere with that process.
* Cisplatin and gemcitabine are approved by the United States Food and Drug Administration to treat certain cancers.
Objectives:
* To determine the optimum doses of AZD2281, cisplatin and gemcitabine in combination that can safely be given to patients with solid tumor cancers.
* To evaluate the response of the tumor to the drug combination and determine the side effects of the treatment.
Eligibility:
-Patients 18 years or older with an advanced solid tumor cancer for whom standard treatments are not effective.
Design:
* In this dose escalation study, the first small group of patients receives the smallest study doses of the study drugs. Subsequent groups receive incrementally higher doses as long as the preceding group does not experience unacceptable side effects. When the highest safe dose is determined, additional patients entering the study receive that dose.
* Patients receive treatment in 21-day cycles as follows:
* Days 1-4: AZD2281 by mouth twice a day
* Day 3: gemcitabine thorough a vein over 1 hour; then cisplatin through a vein over 1 hour.
* Day 10: gemcitabine through a vein over 1 hour.
* Evaluations during treatment include the following:
* Physical examination, vital signs check and blood tests every 3 weeks.
* CT scans every 6 weeks to evaluate the tumor.
* Treatment may continue until it is no longer beneficial.
Detailed Description:
Background:
* Poly (ADP-ribose) polymerase-enzyme (PARP-1) recognizes and rapidly binds to DNA single- and double-strand breaks and has been shown to participate in other DNA-related functions, including gene amplification, cell division, differentiation, apoptosis, and DNA base-excision repair.
* Increased PARP activity is one of the mechanisms by which tumor cells avoid apoptosis caused by DNA damaging agents, and drug resistance has been linked to higher expressions of PARP in cancer cells. This differential expression of PARP supports the observed selectivity of PARP inhibitors to affect proliferating tumor cells. AZD2281 is an orally administered potent inhibitor of PARP-1 and PARP-2, and its combination with cisplatin and gemcitabine may overcome some of the resistance associated with these agents.
Primary Objectives:
* Establish the safety, tolerability, and maximum tolerated dose (MTD) of AZD2281 in combination with cisplatin and gemcitabine in patients with solid tumors.
* Evaluate the effect of cisplatin-gemcitabine, with or without AZD2281, on PAR and gamma- H2AX levels in tumor biopsies and peripheral blood mononuclear cells (PBMCs) pre- and post-treatment.
Secondary Objectives:
\- Evaluate the pharmacokinetics (PK) of AZD2281 with and without cisplatin and gemcitabine.
Eligibility:
* Patients (greater than or equal to 18 years) must have histologically confirmed solid tumor malignancy that is metastatic or unresectable for which standard curative measures do not exist, or are associated with minimal patient survival benefit.
* Patients who have previously received cisplatin or gemcitabine, or both, are eligible.
Design:
* Cycle 1 and subsequent cycles: AZD2281 will be administered orally every 12 hours (Q 12 hours) on day 1, while gemcitabine will be administered intravenously (IV) over 1 hour (600 mg/m(2)/hour) on day 1 and 8 of each cycle and cisplatin over 1 hour on day 1 after gemcitabine.
* Dose escalation will proceed in cohorts of 3 6 patients to a minimum of 27 and a maximum of 42 patients.
* Patients will have a maximum of six cycles of treatment.
* Tumor biopsies will be collected in cycle 1 only, while blood for PBMC samples will be collected in cycle 1 and before drug administration, 24 and 48 hours post administration, in cycle 2, day 1. If Dose Level 3 is achieved additional time points will be collected in cycle 1, day 8 - before drug administration, 6, 24 and 48 hours
post.
* Poly (ADP-ribose) polymerase-enzyme (PARP-1) recognizes and rapidly binds to DNA single- and double-strand breaks and has been shown to participate in other DNA-related functions, including gene amplification, cell division, differentiation, apoptosis, and DNA base-excision repair.
* Increased PARP activity is one of the mechanisms by which tumor cells avoid apoptosis caused by DNA damaging agents, and drug resistance has been linked to higher expressions of PARP in cancer cells. This differential expression of PARP supports the observed selectivity of PARP inhibitors to affect proliferating tumor cells. AZD2281 is an orally administered potent inhibitor of PARP-1 and PARP-2, and its combination with cisplatin and gemcitabine may overcome some of the resistance associated with these agents.
Primary Objectives:
* Establish the safety, tolerability, and maximum tolerated dose (MTD) of AZD2281 in combination with cisplatin and gemcitabine in patients with solid tumors.
* Evaluate the effect of cisplatin-gemcitabine, with or without AZD2281, on PAR and gamma- H2AX levels in tumor biopsies and peripheral blood mononuclear cells (PBMCs) pre- and post-treatment.
Secondary Objectives:
\- Evaluate the pharmacokinetics (PK) of AZD2281 with and without cisplatin and gemcitabine.
Eligibility:
* Patients (greater than or equal to 18 years) must have histologically confirmed solid tumor malignancy that is metastatic or unresectable for which standard curative measures do not exist, or are associated with minimal patient survival benefit.
* Patients who have previously received cisplatin or gemcitabine, or both, are eligible.
Design:
* Cycle 1 and subsequent cycles: AZD2281 will be administered orally every 12 hours (Q 12 hours) on day 1, while gemcitabine will be administered intravenously (IV) over 1 hour (600 mg/m(2)/hour) on day 1 and 8 of each cycle and cisplatin over 1 hour on day 1 after gemcitabine.
* Dose escalation will proceed in cohorts of 3 6 patients to a minimum of 27 and a maximum of 42 patients.
* Patients will have a maximum of six cycles of treatment.
* Tumor biopsies will be collected in cycle 1 only, while blood for PBMC samples will be collected in cycle 1 and before drug administration, 24 and 48 hours post administration, in cycle 2, day 1. If Dose Level 3 is achieved additional time points will be collected in cycle 1, day 8 - before drug administration, 6, 24 and 48 hours
post.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 08-C-0128 | None | None | View |