Olaparib for Kidney Cancer (ORCHID Trial)
Palo Alto (17 mi)Overseen byMark C Markowski, MD, Ph.D
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
No Placebo Group
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?Single arm, single site, open-label Phase II study of the effects of oral olaparib in participants with metastatic renal cell carcinoma that harbor an inactivating mutation in BAP-1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L who have had prior treatment with at least one immune checkpoint inhibitor or anti-VEGF therapy. Must have measurable disease on CT imaging per RECIST 1.1 criteria.
What data supports the idea that Olaparib for Kidney Cancer is an effective drug?The available research does not provide specific data on Olaparib for Kidney Cancer. Instead, it focuses on other drugs like pazopanib and sunitinib, which are used to treat kidney cancer. These studies show that pazopanib and sunitinib have similar effectiveness in terms of how long patients live without the cancer getting worse. Pazopanib is preferred by patients and doctors because it offers a better quality of life and causes less fatigue compared to sunitinib. However, there is no direct information about Olaparib's effectiveness for kidney cancer in the provided research.257910
Is the drug Olaparib a promising treatment for kidney cancer?The provided research articles do not mention Olaparib or its effects on kidney cancer, so we cannot determine if it is a promising treatment based on this information.4671012
What safety data is available for Olaparib in kidney cancer treatment?The provided research does not contain specific safety data for Olaparib (Lynparza) in the treatment of kidney cancer. The studies focus on pazopanib and other anti-VEGF treatments for renal cell carcinoma, discussing their safety profiles and adverse events. For Olaparib, you may need to look for studies or clinical trials specifically evaluating its safety in kidney cancer.1381113
Do I need to stop my current medications to join the trial?The trial requires a washout period for certain medications. You must stop using strong or moderate CYP3A inhibitors 2 weeks before starting olaparib, and strong or moderate CYP3A inducers 3 to 5 weeks prior, depending on the specific drug. If you need to take these during the study, a dose reduction of olaparib might be allowed. Other medications are not specifically mentioned, so consult with the trial team for guidance.
Eligibility Criteria
Adults with metastatic renal cell carcinoma and specific gene mutations who've had prior anti-cancer treatments can join. They must have a certain level of blood counts, organ function, and life expectancy. Women should not be pregnant or breastfeeding, and men must use contraception.Inclusion Criteria
I have been treated with medication that stops tumors from making new blood vessels or boosts my immune system.
I have a mutation in one of the specified genes.
I am fully active and can carry on all my pre-disease activities without restriction.
I will use a condom during and for 3 months after treatment if my partner is pregnant or can become pregnant.
My kidneys work well enough, with a creatinine clearance of 40 mL/min or more.
I have been diagnosed with renal cell carcinoma.
My kidney cancer has spread to other parts of my body.
Exclusion Criteria
I cannot take pills by mouth or have stomach issues that affect medication absorption.
I have been diagnosed with MDS, AML, or have symptoms suggesting these conditions.
I am not currently using strong or moderate CYP3A inhibitors, or can stop them for 2 weeks before starting olaparib.
I do not have active hepatitis B or C.
I have never been treated with a PARP inhibitor like olaparib.
I haven't had chemotherapy or radiotherapy (except for comfort care) in the last 3 weeks.
I have not had major surgery in the last 2 weeks or have fully recovered from it.
I have had a bone marrow or double cord blood transplant.
I have lasting side effects from cancer treatment, but not hair loss.
I am not currently using certain strong or moderate drugs that affect drug metabolism.
I have a serious health condition that is not under control.
Treatment Details
The trial is testing the oral drug Olaparib in patients with kidney cancer that has spread and contains certain DNA repair gene mutations. It's an open-label Phase II study where all participants receive the medication to see how it affects their cancer.
1Treatment groups
Experimental Treatment
Group I: OlaparibExperimental Treatment1 Intervention
Participants with metastatic renal cell carcinoma that harbor an inactivating mutation in BAP-1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L that have had prior treatment with at least one immune checkpoint inhibitor or anti-VEGF therapy with measureable disease on CT imaging according to RECIST 1.1 criteria. Participants will be initially treated with olaparib 150mg by mouth twice daily for one month. After one month of therapy, the dose will be increased to 300mg by mouth twice daily provided there are no grade 3 or greater adverse events experienced. Reassessment will occur at least monthly for toxicity. Radiological scans will be performed every 3 months to assess disease response. Treatment will be continued until clinical and/or radiographic progression according to RECIST 1.1 criteria or unmanageable toxicity requiring cessation.
Olaparib is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Lynparza for:
- Breast cancer
- Ovarian cancer
- Fallopian tube cancer
- Peritoneal cancer
- Pancreatic cancer
- Prostate cancer
- Endometrial cancer
🇺🇸 Approved in United States as Lynparza for:
- Ovarian, fallopian tube, and primary peritoneal cancer
- Breast cancer
- Prostate cancer
- Pancreatic cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
Johns Hopkins Sidney Kimmel Comprehensive Cancer CenterBaltimore, MD
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Who is running the clinical trial?
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsLead Sponsor
AstraZenecaIndustry Sponsor
References
Pazopanib: an antiangiogenic drug in perspective. [2021]Pazopanib, a tyrosine kinase inhibitor targeted to angiogenesis, has been tested in preclinical and clinical trials and has shown promising activity against a variety of solid tumors, such as renal cancer, all of which are related to the angiogenic pathway. It has a safety profile related to this mechanism of action. Diarrhea, hypertension, hair depigmentation and nausea are the most common side effects. Pazopanib is currently under evaluation as monotherapy and in combination with some potentially synergistic agents of proven activity.
New advancements and developments in treatment of renal cell carcinoma: focus on pazopanib. [2021]With the recent approval of pazopanib, an oral multitargeted tyrosine kinase inhibitor which potently targets vascular endothelial growth factor receptors 1-3, platelet-derived growth factor, and c-kit, six agents are now available for use in the management of metastatic renal cell carcinoma (RCC). Pazopanib has shown improved progression-free survival compared with placebo in treatment-naïve or cytokine-treated patients with metastatic RCC in large Phase II and Phase III clinical trials. Pazopanib has demonstrated a tolerable side effect profile and is currently being compared with sunitinib in a Phase III noninferiority trial. In this review, the outcomes of the clinical testing of pazopanib are discussed, as well as a perspective on the placement of pazopanib among other approved agents.
The European Medicines Agency review of pazopanib for the treatment of advanced renal cell carcinoma: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. [2021]On June 14, 2010, the European Commission issued a conditional marketing authorization valid throughout the European Union for pazopanib for the treatment of advanced renal cell carcinoma. Pazopanib is an antineoplastic agent that inhibits multiple receptor tyrosine kinases. The recommended oral dose is 800 mg once daily. The benefit of pazopanib is an increased progression-free survival. In the pivotal trial VEG105192, the median progression-free survival was 9.2 months (95% confidence interval, 7.4-12.9) in the pazopanib arm compared with 4.2 months (95% confidence interval, 2.8-4.2) in the placebo arm. The most common side effects include diarrhea, hair color change, hypertension, nausea, fatigue, anorexia, vomiting, dysgeusia, elevated alanine aminotransferase, elevated aspartate aminotransferase, and abdominal pain. The objective of this article is to summarize the scientific review of the application that led to approval in the European Union.
A comprehensive overview of targeted therapy in metastatic renal cell carcinoma. [2021]Chemotherapy and immunotherapy failed to deliver decisive results in the systemic treatment of metastatic renal cell carcinoma. Agents representing the current standards operate on members of the RAS signal transduction pathway. Sunitinib (targeting vascular endothelial growth factor), temsirolimus (an inhibitor of the mammalian target of rapamycin - mTOR) and pazopanib (a multi-targeted receptor tyrosine kinase inhibitor) are used in the first line of recurrent disease. A combination of bevacizumab (inhibition of angiogenesis) plus interferon α is also first-line therapy. Second line options include everolimus (another mTOR inhibitor) as well as tyrosine kinase inhibitors for patients who previously received cytokine. We review the results of clinical investigations focusing on survival benefit for these agents. Additionally, trials focusing on new agents, including the kinase inhibitors axitinib, tivozanib, dovitinib and cediranib and monoclonal antibodies including velociximab are also discussed. In addition to published outcomes we also include follow-up and interim results of ongoing clinical trials. In summary, we give a comprehensive overview of current advances in the systemic treatment of metastatic renal cell carcinoma.
Targeted therapy of kidney cancer: keeping the art around the algorithms. [2017]Therapy for metastatic kidney cancer is actively evolving, particularly in the results of registration drug trials that have led to the approval of vascular endothelial growth factor pathway drugs such as sorafenib, sunitinib, pazopanib, bevacizumab, and axitinib, with focus on patients with good- or intermediate-risk criteria and clear cell histology. Mammalian target of rapamycin (mTOR) drugs such as everolimus and temsirolimus pivotal trials emphasize experiences in the setting of prior treatment or high-risk features. Interferon and interleukin 2 also are part of the treatment algorithms.
Pazopanib and anti-VEGF therapy. [2021]Pazopanib (Votrient™, GlaxoSmithKline), a multi-kinase inhibitor with activity against VEGFR and other receptors, was recently approved by the FDA for the treatment of advanced renal cell carcinoma (RCC). Here, we review the history of its development, together with an overview of VEGF and its receptors and co-receptors. Results from selected clinical trial data in RCC and other malignant diseases are presented. Based on available evidence, pazopanib is an effective VEGFR inhibitor with demonstrable clinical activity in metastatic RCC and promising activity in other diseases. Like most kinase inhibitors, its activity is not restricted to VEGF receptors, which is reflected in its side-effect profile.
Persistence and compliance with pazopanib in patients with advanced renal cell carcinoma within a U.S. administrative claims database. [2023]Pazopanib is an oral tyrosine kinase inhibitor with demonstrated efficacy and tolerability in patients with advanced renal cell carcinoma (RCC).
Experience with pazopanib in the treatment of metastatic renal cell carcinoma: a monocentric experience. [2021]The aim of the study was to assess the activity and the safety of pazopanib as first-line therapy in patients with metastatic renal cell carcinoma.
Cost-effectiveness of pazopanib versus sunitinib for renal cancer in the United States. [2023]Current first-line treatments for metastatic renal cell carcinoma (mRCC) include the multityrosine kinase inhibitors pazopanib and sunitinib. Both agents had similar progression-free survival (PFS) and overall survival (OS) in the COMPARZ trial (Comparing the Efficacy, Safety and Tolerability of Pazopanib versus Sunitinib); however, the adverse event profiles of the 2 agents are different. In the PISCES trial (Patient Preference Study of Pazopanib versus Sunitinib in Advanced or Metastatic Kidney Cancer), patients and physicians preferred pazopanib primarily because it offered better health-related quality of life (HRQoL) and caused less fatigue.
Quality-adjusted time without symptoms or toxicity analysis of pazopanib versus sunitinib in patients with renal cell carcinoma. [2021]In a phase 3, randomized, open-label trial (Pazopanib versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma, COMPARZ; NCT00720941), pazopanib was found to be noninferior to sunitinib in terms of progression-free survival in patients with metastatic renal cell carcinoma with no prior therapy. Overall treatment differences were evaluated in a post hoc analysis with a quality-adjusted time without symptoms or toxicity (Q-TWiST) methodology.
Occurrence of hepatotoxicity with pazopanib and other anti-VEGF treatments for renal cell carcinoma: an observational study utilizing a distributed database network. [2022]To quantify the hepatic safety of pazopanib and comparator anti-vascular endothelial growth factor (VEGF) therapies in clinical practice among renal cell carcinoma (RCC) patients.
COMPARZ Post Hoc Analysis: Characterizing Pazopanib Responders With Advanced Renal Cell Carcinoma. [2021]The phase III COMPARZ study showed noninferior efficacy of pazopanib versus sunitinib in advanced renal cell carcinoma. In this COMPARZ post hoc analysis we characterized pazopanib responders, patient subgroups with better outcomes, and the effect of dose modification on efficacy and safety.
Analysis of Anti-Angiogenesis-Related Adverse Events Associated with Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitors (VEGFR-TKIs) in Patients with Metastatic Renal Cell Carcinoma. [2023]Limited studies have evaluated anti-angiogenesis-related adverse events involving oral vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) in metastatic renal cell carcinoma using real-world data.