NCT00678132

AZD2281 and Cisplatin Plus Gemcitabine to Treat Solid Tumor Cancers

Completed Phase 1 Last updated 5 July 2018

What this trial tests

Phase 1 trial testing AZD 2281 in Neoplasms in 23 participants. Completed in 23 November 2010.

Timeline

24 April 2008

Primary endpoint
23 November 2010

23 November 2010

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	23
Start date	24 April 2008
Primary completion	23 November 2010
Estimated completion	23 November 2010
Sites	1 location across United States

Drugs / interventions tested

• AZD 2281 — full drug profile →
• Cisplatin (cisplatin) — full drug profile →
• Gemcitabine (gemcitabine) — full drug profile →

Conditions studied

• Neoplasms — all drugs for Neoplasms →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. A phase I combination study of olaparib with cisplatin and gemcitabine in adults with solid tumors.
   Rajan A, Carter CA, Kelly RJ, Gutierrez M, et al · · 2012 · cited 122× · PMID 22371451 · DOI 10.1158/1078-0432.ccr-11-2425
2. Dancing with the DNA damage response: next-generation anti-cancer therapeutic strategies.
   Minchom A, Aversa C, Lopez J. · · 2018 · cited 97× · PMID 30023007 · DOI 10.1177/1758835918786658
3. Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions.
   Basourakos SP, Li L, Aparicio AM, Corn PG, et al · · 2017 · cited 91× · PMID 27978798 · DOI 10.2174/0929867323666161214114948
4. Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment.
   Kiss RC, Xia F, Acklin S. · · 2021 · cited 90× · PMID 34360968 · DOI 10.3390/ijms22158199
5. Advances and perspectives of PARP inhibitors.
   Yi M, Dong B, Qin S, Chu Q, et al · · 2019 · cited 83× · PMID 31737426 · DOI 10.1186/s40164-019-0154-9
6. Poly(ADP-ribose) polymerase inhibitors in triple-negative breast cancer.
   Comen EA, Robson M. · · 2010 · cited 37× · PMID 20164690 · DOI 10.1097/ppo.0b013e3181cf01eb