Trial record 7 of 99 for:    small cell lung ca | Open Studies

Cediranib Maleate and Olaparib in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2015 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02498613
First received: July 14, 2015
Last updated: NA
Last verified: July 2015
History: No changes posted
  Purpose

This phase II trial studies cediranib maleate in combination with olaparib in treating patients with solid tumors that have spread to other parts of the body or cannot be removed by surgery, including breast cancer, non-small cell lung cancer, small cell lung cancer, and pancreatic cancer. Cediranib maleate and olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cediranib maleate may also block the flow of oxygen to the tumor, and may help make the tumor more sensitive to olaparib.


Condition Intervention Phase
Estrogen Receptor Negative
HER2/Neu Negative
Metastatic Pancreatic Adenocarcinoma
Pancreatic Adenocarcinoma
Progesterone Receptor Negative
Recurrent Breast Carcinoma
Recurrent Non-Small Cell Lung Carcinoma
Recurrent Pancreatic Carcinoma
Recurrent Small Cell Lung Carcinoma
Stage III Pancreatic Cancer
Stage IIIA Breast Cancer
Stage IIIA Non-Small Cell Lung Cancer
Stage IIIA Small Cell Lung Carcinoma
Stage IIIB Non-Small Cell Lung Cancer
Stage IIIB Small Cell Lung Carcinoma
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Stage IV Non-Small Cell Lung Cancer
Stage IV Small Cell Lung Carcinoma
Stage IVA Pancreatic Cancer
Stage IVB Pancreatic Cancer
Triple-Negative Breast Carcinoma
Other: 18F-Fluoromisonidazole
Drug: Cediranib Maleate
Other: Laboratory Biomarker Analysis
Drug: Olaparib
Procedure: Positron Emission Tomography
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • ORR, measured by RECIST v 1.1 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    The exact two-sided 95% confidence interval for the ORR will be reported.


Secondary Outcome Measures:
  • Incidence of toxicity, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]
    Adverse medical events will be tabulated. NCI toxicity grade 3 and grade 4 laboratory abnormalities will be listed.

  • PFS [ Time Frame: The duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method with the 95% confidence intervals (CIs). The Rothman CI, CI based on the Greenwoods variance, Thomas and Grunkemeier CI and the simultaneous confidence bands by Nair and Hall and Wellner will be reported. The possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.


Other Outcome Measures:
  • Biomarker data [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    The biomarker data analysis including miRNAs data will be completed using the Lasso based elastic net method. The penalty parameter that controls the shrinkage of fixed terms and the variable selection will be determined by k-fold cross validation. Due to the limited sample size, the biomarker data analysis is for the exploratory research only.

  • PET imaging data [ Time Frame: Up to day 4 ] [ Designated as safety issue: No ]
    The general non-linear and generalized non-liner model will be used to analyze PET imaging data.


Estimated Enrollment: 121
Study Start Date: January 2016
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cediranib maleate, olaparib)
Patients receive cediranib maleate PO QD for 3-4 days and then undergo biopsy. After biopsy, patients continue to receive cediranib maleate PO QD and begin olaparib PO BID on the day after the post-dose biopsy (day 4-7) or by day 8 of course 1 (biopsy cohorts-NSCLC and TNBC) or day 4 of course 1 (non-biopsy cohorts-PDAC and SCLC). Courses repeat every 28 days (35 days for course 1) in the absence of disease progression or unacceptable toxicity.
Other: 18F-Fluoromisonidazole
Correlative studies
Other Names:
  • 18F-fluoromisonidazole
  • 18F-MISO
  • 18F-Misonidazole
  • FMISO
Drug: Cediranib Maleate
Given PO
Other Names:
  • AZD2171
  • AZD2171 Maleate
  • CEDIRANIB MALEATE
  • Recentin
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Olaparib
Given PO
Other Names:
  • AZD2281
  • KU-0059436
  • Lynparza
  • OLAPARIB
  • PARP Inhibitor AZD2281
Procedure: Positron Emission Tomography
Correlative studies
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET SCAN
  • Positron Emission Tomography
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically confirmed, metastatic or unresectable malignancy of the following types: (a) non-squamous, non-small cell lung cancer (NSCLC), (b) triple-negative breast cancer (TNBC) without germline BRCA mutation, (c) pancreatic adenocarcinoma (PDAC), or (d) small cell lung cancer (SCLC)
  • For NSCLC patients only:

    • Must be willing to undergo paired FMISO PET scans
    • Must be willing to undergo paired biopsies
    • Must have had prior chemotherapy including platinum-based regimen and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor(s) (TKI[s]) or anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitors if sensitizing mutations are present
  • For TNBC patients only

    • Must be known germline BRCA wild-type; BRCA mutation carriers are excluded; if unknown, then BRCA testing must be performed in a clinical Clinical Laboratory Improvement Amendments (CLIA) certified lab
    • Must have tumor amenable for, and be willing to undergo, baseline and on-treatment biopsies
    • Must have received at least 1 prior chemotherapy regimen in the metastatic setting
  • For PDAC patients only

    • Must have received at least one standard chemotherapy either with or without radiation therapy
  • For SCLC patients only

    • Must have had a standard platinum-based regimen for limited or extensive stage disease
  • FOR ALL PATIENTS
  • Patients must have measurable disease by RECIST v1.1
  • Toxicities of prior therapy (except alopecia) should be resolved to =< grade 1 as per National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0; patients with long-standing stable grade 2 neuropathy may be considered after discussion with the study Principal Investigator (PI)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >= 70%)
  • Life expectancy of >= 4 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin > 9 g/dL
  • Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Proteinuria less than or equal to 1+ proteinuria on two consecutive dipsticks taken no less than week apart, or < 1 g protein on 24-hour urine collection or a urine protein:creatinine ratio of < 1
  • Troponin T or I within normal institutional limits
  • International normalized ration (INR) within 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed
  • Activated partial thromboplastin time (aPTT) within 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed
  • Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
  • Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid stimulating hormone (TSH) within normal limits
  • Adequately controlled blood pressure (BP) < 140 mmHg (systolic) and < 90 mmHg (diastolic) taken in the clinic setting by a medical professional within 2 weeks prior to starting study; patients with hypertension may be managed with up to a maximum of 3 antihypertensive medications; patients who are on 3 antihypertensive medications are highly recommended to be followed by a cardiologist or blood pressure specialist for management of BP while on protocol
  • Patients who have the following risk factors are considered to be at increased risk for cardiac toxicities, and must have documented left ventricular ejection fraction (LVEF) by echocardiogram greater than institution's lower limit of normal (or 55% if threshold for normal not otherwise specified by institutional guidelines) obtained within 6 months

    • Prior treatment with anthracyclines
    • Prior treatment with trastuzumab
    • A New York Heart Association (NYHA) classification of II controlled with treatment
    • Prior central thoracic radiation therapy (RT), including RT to the heart
    • History of myocardial infarction within 12 months (patients with history of myocardial infarction within 6 months are excluded from the study)
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; 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 4 months after completion of cediranib and olaparib administration
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients with known deleterious BRCA germline mutation by standard clinical testing are excluded; for TNBC patients, BRCA germline testing is required, if not performed previously; for the other cohorts, BRCA germline testing is not required
  • Patients who have had chemotherapy or RT within 3 weeks prior to start of the study agents, or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
  • Patients should not have received any other investigational agents within the past 4 weeks
  • Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should be excluded from this clinical trial; screening imaging to rule out brain metastases is not required, but should be performed prior to study enrollment if clinically indicated; patients with treated brain metastases and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least 1 month following radiotherapy prior to starting study drug
  • Patients who have received prior inhibitor of VEGF signaling and a poly (ADP-ribose) polymerases (PARP) inhibitor administered in combination; unless administered in combination, patients who received a prior PARP inhibitor or a prior VEGF-signaling inhibitor agent are allowed after discussing with the PI
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib or olaparib
  • Participants receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; dihydropyridine calcium-channel blockers are permitted for management of hypertension
  • Current use of natural herbal products or other "folk remedies;" if using previously, patients must stop using natural herbal products while participating in this study
  • Patients with concomitant or prior invasive malignancies within the past 3 years; subjects with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible
  • 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
  • Patients with corrected QT interval (QTc) (with Bazett's correction) prolongation > 470 msec or other significant electrocardiogram (ECG) abnormality noted within 14 days of treatment
  • History of myocardial infarction within 6 months
  • History of stroke or transient ischemic attack within 6 months
  • NYHA classification of III or IV
  • Current condition requiring concurrent use of drugs or biologics with anti-arrhythmic or pro-arrhythmic potential
  • History of hypertensive crisis or hypertensive encephalopathy within 3 years
  • Clinically significant peripheral vascular disease or vascular disease (abdominal aortic aneurysm (> 5 cm) or aortic dissection)
  • A major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib (percutaneous/endobronchial biopsies are allowed)
  • Patients may not have current signs and/or symptoms of bowel obstruction within 1 month prior to starting study drugs, except if it was a temporary incident (improved within < 24 hrs with medical management)
  • History of hemoptysis within the last 1 month
  • Presence of cavitation of central pulmonary lesion
  • History of abdominal fistula, intra-abdominal abscess, or gastrointestinal perforation with the 3 months
  • Patients may not have current dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)
  • Patients may not have evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted
  • Patients may not have features suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with cediranib and olaparib
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02498613

Locations
United States, Connecticut
Yale University Cancer Center LAO Not yet recruiting
New Haven, Connecticut, United States, 06520
Contact: Joseph W. Kim    203-737-6467    joseph.w.kim@yale.edu   
Principal Investigator: Joseph W. Kim         
Sponsors and Collaborators
Investigators
Principal Investigator: Joseph Kim Yale University Cancer Center LAO
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02498613     History of Changes
Other Study ID Numbers: NCI-2015-01097, NCI-2015-01097, 9881, 9881, P30CA016359, UM1CA186689
Study First Received: July 14, 2015
Last Updated: July 14, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Small Cell Lung Carcinoma
Lung Diseases
Adenocarcinoma
Breast Neoplasms
Carcinoma
Pancreatic Neoplasms
Breast Diseases
Bronchial Neoplasms
Carcinoma, Bronchogenic
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Pancreatic Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Skin Diseases
Thoracic Neoplasms
Cediranib
Fluoromisonidazole
Maleic acid
Misonidazole
Anti-Infective Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 27, 2015