Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Breast Neoplasms

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endometrial Neoplasms

Fallopian Tube Neoplasms

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Neoplasms

Uterine Diseases

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Dose esc: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of the trial will be AUC4. Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8. Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis

Randomized: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of the trial will be AUC4. Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8. Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis.

A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of the trial will be AUC4. Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8. Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis.

Jung-Min Lee, M.D.

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.

Background:

* Olaparib (AZD2281) is an oral PARP-1/2 inhibitor (PARPi) that affects tumors by impairing repair of single stranded DNA and causing double strand breaks. Carboplatin covalently crosslinks DNA causing stalled replication forks repaired through nucleotide excision repair and homologous recombination (HR).
* There is no published data on sequence-specificity of PARPi with platinums. Our preclinical data indicate sequence may be important in growth inhibition and DNA damage and repair.
* We have demonstrated activity and safety with concomitant administration of olaparib and carboplatin.
* We hypothesize that elucidation of sequence specificity may improve upon that clinical benefit by optimizing drug administration and potentially safety.

Objectives:

* To determine safe dose of olaparib tablet with carboplatin.
* To estimate the pharmacokinetic (PK) and pharmacodynamic (PD) effects of two schedules of olaparib and carboplatin using peripheral blood mononuclear cells (PBMCs).
* To determine the schedule-associated safety of olaparib and carboplatin in women s cancers.

Eligibility:

* Adult women with recurrent/refractory epithelial ovarian cancer, fallopian, primary peritoneal, uterine papillary serous cancer, or malignant mixed mullerian tumors, or recurrent/refractory breast cancer that is metastatic or unresectable and for which standard therapies do not exist or are no longer effective. BRCA1/2 mutation carriers will be eligible with any metastatic disease.
* Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks.
* ECOG performance status 0-2 and adequate organ and marrow function.

Design:

* A phase I 3 plus 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the trial will be AUC4.
* Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8.
* Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis.
* Research samples will be obtained for PD endpoints prior to and approximately 24 hours after carboplatin infusion and prior to the 1st and 3rd of olaparib.
* Blood samples for olaparib PK will be obtained in all patients after the first dose of olaparib in cycles 1 and 2.
* Patients will be evaluated for toxicity in clinic every 3 weeks and every two cycles for response using RECIST criteria. Imaging studies will be obtained every 3 cycles for patients who stay on the study longer than four years.

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

A Pharmacokinetic/Pharmacodynamic Study With a Phase I Run-In With a PARP Inhibitor (Olaparib) in Combination With Carboplatin for Refractory or Recurrent Women's Cancers

Pharmacodynamic study results and toxicity during Cycle 1 at 24 and 48 hours

National Cancer Institute (NCI)

Diseases and Abnormalities at or Before Birth

Syndrome

Hereditary Breast and Ovarian Cancer Syndrome

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Breast Diseases

Skin Diseases

Patients with ovarian and/or breast cancer

control population without history of breast and/or ovarian cancer

blood collection for research quantification of allelic expression in the gene BRCA1.

blood collection

Agnès HARDOUIN, MD

The purpose of this study is to determine proportion of patients presented a search allelic imbalance of expression of genes BRCA 1 and 2 in population with hereditary breast and/or ovarian cancer risk and negative for deletion mutation BRCA 1 and 2 genes

Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer

The main objective of this study is to estimate the proportion of patients with allelic imbalance at the level of expression of BRCA1 in a population meeting the criteria suggestive of a hereditary predisposition to breast and / or ovarian cancer , and negative for deleterious mutations of BRCA 1 and BRCA 2.

Study the variability of the measurement of the allelic expression depending on the position of SNPs (Single Nucleotide Polymorphism) in the gene, in order to extend this research to variants of unknown significance whatever their position in the gene.

Estimate the proportion of patients with allelic imbalance at the level of expression of the BRCA2 gene in the same population.

The frequency of allelic imbalance of expression will be compared depending on the age of the witnesses in the control population. The potential effect of age on the presence or absence of allelic imbalance of expression will be observed.

Centre Francois Baclesse

Dr Agnès HARDOUIN

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Olaparib in Combination With Carboplatin for Refractory or Recurrent Women s Cancers	NCT01237067	Ovarian Cancer Breast Cancer Primary Periton... Fallopian Tube ... Endometrial Can...	Carboplatin Olaparib	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Olaparib in Combination With Carboplatin for Refractory or Recurrent Women s Cancers	NCT01237067	Ovarian Cancer Breast Cancer Primary Periton... Fallopian Tube ... Endometrial Can...	Carboplatin Olaparib	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Olaparib in Combination With Carboplatin for Refractory or Recurrent Women s Cancers	NCT01237067	Ovarian Cancer Breast Cancer Primary Periton... Fallopian Tube ... Endometrial Can...	Carboplatin Olaparib	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer	NCT01333748	Hereditary Brea...	blood collectio... blood collectio...	18 Years -	Centre Francois Baclesse

Spots Global Cancer Trial Database for brca 1 and brca 2