NCT01237067

Olaparib in Combination With Carboplatin for Refractory or Recurrent Women s Cancers

Completed Phase 1 Last updated 17 December 2019

What this trial tests

Phase 1 trial testing Carboplatin in Ovarian Cancer in 77 participants. Completed in 12 December 2019.

Timeline

7 February 2011

Primary endpoint
16 November 2014

12 December 2019

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	77
Start date	7 February 2011
Primary completion	16 November 2014
Estimated completion	12 December 2019
Sites	1 location across United States

Drugs / interventions tested

• Carboplatin (Carboplatin) — full drug profile →
• Olaparib (olaparib) — full drug profile →

Conditions studied

• Ovarian Cancer — all drugs for Ovarian Cancer →
• Breast Cancer — all drugs for Breast Cancer →
• Primary Peritoneal Cancer — all drugs for Primary Peritoneal Cancer →
• Fallopian Tube Cancer — all drugs for Fallopian Tube Cancer →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 99, any sex, with Ovarian Cancer or Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Background:

\- Olaparib is an experimental anti-cancer drug that is part of a class of drugs called PARP inhibitors. PARP is a protein that is involved in repairing DNA damage, but it may also encourage precancerous cells to develop into cancer cells. Olaparib has been given safely in combination with carboplatin, a drug used to treat breast, ovarian, uterine, and cervical cancer, but more research is needed to determine whether the drugs are more effective when given together or which drug should be given first.

Objectives:

\- To determine the safety and effectiveness of combined carboplatin and olaparib as a treatment for gynecologic (female organ) or breast cancer.

Eligibility:

* Women at least 18 years of age who have breast, ovarian, uterine, or cervical cancer that has not responded to standard treatments.
* Men at least 18 years of age who have metastatic breast cancer and have a BRCA-1/2 mutation.

Design:

* Participants will be screened with a physical examination and medical history, as well as blood and tumor samples and imaging studies as required by the researchers. Study participants will then be divided into two groups.
* Group 1: Participants will receive olaparib tablets twice a day for 7 days (14 doses) and will receive carboplatin by vein on day 1 or 2, for a 21-day treatment cycle. Group 1 study is designed to determine the safety of new tablet formulation of olaparib.
* Group 2: Participants will be divided into two smaller groups, with reversed treatment schedules. Group 2 study is designed to evaluate which drug should be given first through endpoint studies in blood samples.
* Group 2A: Participants will receive olaparib tablets twice a day for 7 days (14 doses) and then carboplatin on day 8 of the first cycle. Cycle 2 will start with carboplatin on day 1 and olaparib starting on day 2 for 7 days (14 doses).
* Group 2B: Participants will receive carboplatin on the first day of the first cycle, and then olaparib on day 2, twice a day for 7 days (14 doses) of the first cycle. Cycle 2 will start with 7 days of olaparib (14 doses) and carboplatin will be given on day 8.
* From cycle 3 until completion of therapy, all Group 2 participants will follow the schedule used for Group 1 (carboplatin on day 1 or 2 of the week of olaparib therapy, also in 21-day cycles).
* Additional blood and tissue samples and imaging studies will be conducted throughout the treatment period.
* All participants may receive no more than 8 cycles of olaparib and carboplatin therapy, but may continue to take olaparib if their cancer responds to the treatment.

Publications & conference data

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

1. Targeting DNA damage response in cancer therapy.
   Hosoya N, Miyagawa K. · · 2014 · cited 232× · PMID 24484288 · DOI 10.1111/cas.12366
2. New strategies for triple-negative breast cancer--deciphering the heterogeneity.
   Mayer IA, Abramson VG, Lehmann BD, Pietenpol JA. · · 2014 · cited 227× · PMID 24536073 · DOI 10.1158/1078-0432.ccr-13-0583
3. PARP Inhibitors as a Therapeutic Agent for Homologous Recombination Deficiency in Breast Cancers.
   Keung MYT, Wu Y, Vadgama JV. · · 2019 · cited 104× · PMID 30934991 · DOI 10.3390/jcm8040435
4. PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation.
   Min A, Im SA. · · 2020 · cited 97× · PMID 32046300 · DOI 10.3390/cancers12020394
5. 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
6. Use of poly ADP-ribose polymerase [PARP] inhibitors in cancer cells bearing DDR defects: the rationale for their inclusion in the clinic.
   Cerrato A, Morra F, Celetti A. · · 2016 · cited 89× · PMID 27884198 · DOI 10.1186/s13046-016-0456-2
7. The genomics and genetics of endometrial cancer.
   O'Hara AJ, Bell DW. · · 2012 · cited 86× · PMID 22888282 · DOI 10.2147/agg.s28953
8. An update on PARP inhibitors for the treatment of cancer.
   Benafif S, Hall M. · · 2015 · cited 78× · PMID 25750544 · DOI 10.2147/ott.s30793