Trial record 4 of 4 for:
parp prostate cancer | Open Studies
Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations
This study is currently recruiting participants.
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
First received: November 16, 2013
Last updated: April 11, 2014
Last verified: November 2013
- The poly (ADP-ribose) polymerase (PARP) family of enzymes is critical for maintaining genomic stability by regulating a variety of DNA damage repair mechanisms.
- BMN 673 is a PARP inhibitor with greater in vitro activity than any other PARP inhibitor currently in development. BMN 673 has been shown to cause single-agent synthetic lethality in BRCA1/2- and PTEN-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in DNA repair pathways.
- BMN 673 is showing promising single-agent activity in patients with advanced ovarian and breast cancer harboring deleterious BRCA mutations.
- This pilot study will evaluate the pharmacodynamic effects of BMN 673 on DNA damage and apoptosis markers in tumor biopsy tissue.
-Determine the pharmacodynamic effect of BMN 673 in tumor biopsies from patients with advanced ovarian, breast, or other solid tumor and deleterious BRCA mutations.
- Determine the response rate (CR + PR) of treatment with BMN 673 in patients with advanced ovarian or primary peritoneal carcinoma and deleterious BRCA mutations.
- Determine the response rate (CR + PR) of treatment with BMN 673 in patients with advanced breast carcinoma and deleterious BRCA mutations.
- Determine the response rate (CR + PR) of treatment with BMN 673 in patients with advanced solid tumor (other than breast or ovarian) and deleterious BRCA mutations.
- Adult patients with documented deleterious BRCA 1 or 2 mutations with histologically confirmed ovarian, primary peritoneal, breast, prostate, pancreas, gastric or other solid tumor whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options.
- No major surgery, radiation, or chemotherapy within 4 weeks prior to study enrollment, and recovered from toxicities of prior therapies to at least eligibility levels.
- Age greater than or equal to 18 years of age; ECOG performance status less than equal to 2
- Adequate organ function.
- Willingness to undergo tumor biopsies.
- BMN 673 is administered orally each day in 28-day cycles
- Tumor biopsies will be performed at baseline (pre-treatment) and 3-6 hrs post dose on cycle 1 day 8. An optional tumor biopsy may also be collected at time of disease progression. Tumor biopsies will be evaluated for PAR levels, DNA damage response markers such as >=H2AX, cleaved caspase 3, ERCC1, pNbs1, XPF, RAD51, and pT1989ATR, and, as indicators of ATR/ATM activation, chk1 and chk2
- Blood samples for CTC analyses will be collected at baseline (pre-treatment), on cycle 1 day 1(3-6 hours post dose), on cycle 1 day 8 (3-6 hours post dose), and on cycle 2 day 1 (3-6 hours post dose)
- Blood samples for PK analysis will be collected on cycle 1 day 1 pre-dose and 0.5, 1, 2, 3, 4, 6,8, and 24 hours post-dose, on cycle 1 day 8 (3-6 hours post dose), and on cycle 2 day 1 predose and 3-6 hours post dose.
Advanced Ovarian Cancer
Primary Peritoneal Cancer
Advanced Breast Cancer
Advanced Solid Tumors
Drug: BMN 673
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations
Primary Outcome Measures:
- Determine the pharmacodynamic effect of BMN 673 in tumor biopsies from patients with advanced ovarian, breast, or other solid tumor and deleterious BRCA mutations. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Determine the response rate (CR + PR) of treatment with BMN 673 in patients with eligible cancers and deleterious BRCA mutations. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||August 2016 (Final data collection date for primary outcome measure)
Drug: BMN 673
Oral, daily administration
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Adult patients with documented deleterious BRCA 1 or 2 mutations with histologically confirmed ovarian, primary peritoneal, breast, prostate, pancreas, gastric or other solid tumor whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options.
Patients should be either platinum-na(SqrRoot) ve or should have received platinum-based therapy at least 6 months or greater prior to the time of enrollment; patients who received platinum as part of adjuvant therapy should not have had recurrent disease within 6 months of completing adjuvant therapy.
Patients with metastatic disease must have received at least one line of standard of care (SOC) treatment for metastatic disease prior to enrollment
- Age greater than or equal to 18 years of age.
- ECOG performance status less than or equal to 2
- Life expectancy of greater than 3 months.
- Patients must have normal organ and marrow function as defined below:
- leukocytes greater than or equal to 3,000/mcL
- absolute neutrophil count greater than or equal to 1,500/mcL
- platelets greater than or equal to 100,000/mcL
- total bilirubin less than or equal to 1.5 times institutional upper limit of normal
- AST(SGOT)/ALT(SGPT) less than or equal to 3 times institutional upper limit of normal
- creatinine less than or equal to 1.5 times institutional upper limit of normal
-creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
The effects of BMN 673 on the developing human fetus are unknown. For this reason and because PARP inhibitors are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after completing study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 3 months after completion of BMN 673 administration.
- Patients must be able to swallow whole tablets or capsules. Nasogastric or G-tube administration is not allowed. Any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed.
- Ability to understand and the willingness to sign a written informed consent document.
- Patients with HER2-positive advanced breast cancer or ovarian cancer should have received at least two lines of systemic therapy in the advanced setting.
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients who have had prior treatment with any PARP inhibitors are ineligible.
- Patients who are receiving any other investigational agents.
- Patients with known active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients whose brain metastatic disease status has remained stable for greater than or equal to 4 weeks following treatment of brain metastases are eligible to participate at the discretion of the principal investigator.
- Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of BMN 673 will be determined following review by the principal investigator.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with BMN 673. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- Patients at increased risk of bleeding, including patients currently receiving warfarin or other anti-coagulants.
- Women who are currently lactating
Please refer to this study by its ClinicalTrials.gov identifier: NCT01989546
|National Institutes of Health Clinical Center, 9000 Rockville Pike
|Bethesda, Maryland, United States, 20892 |
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937 |
||Shivaani Kummar, M.D.
||National Cancer Institute (NCI)
||National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||November 16, 2013
||April 11, 2014
||United States: Federal Government
Keywords provided by National Institutes of Health Clinical Center (CC):
Advanced Solid Tumors
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on April 17, 2014
Neoplasms by Site
Endocrine Gland Neoplasms
Genital Neoplasms, Female
Digestive System Neoplasms
Genital Diseases, Female
Endocrine System Diseases
Digestive System Diseases