Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Carcinoma

Small Cell Lung Carcinoma

Pancreatic Neoplasms

Adenocarcinoma

Carcinoma, Small Cell

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Small Cell Lung Cancer

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Maleic acid

Misonidazole

Cediranib

Enzyme Inhibitors

Protein Kinase Inhibitors

Antiprotozoal Agents

Antiparasitic Agents

Patients receive cediranib maleate PO QD on day 1. Patients undergoing FMISO scan also receive olaparib PO BID beginning the day after the second FMISO scan and the rest of the patients receive olaparib PO BID beginning day 4 of cycle 1. Cycles repeat every 28 days (35 days for cycle 1) in the absence of disease progression or unacceptable toxicity.

18F-Fluoromisonidazole

Cediranib Maleate

Laboratory Biomarker Analysis

Positron Emission Tomography

Joseph W Kim

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 (advanced/metastatic) or cannot be removed by surgery (unresectable), 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.

PRIMARY OBJECTIVE:

I. To determine the objective response rate (ORR) of cediranib (cediranib maleate) plus olaparib in combination in patients with advanced or metastatic solid tumors of the following tumor types: non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), pancreatic ductal adenocarcinoma (PDAC), and small cell lung cancer (SCLC).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of oral administration of cediranib in combination with olaparib in patients with select advanced solid tumors.

II. To estimate progression free survival (PFS) in each tumor cohort.

EXPLORATORY OBJECTIVES:

I. To estimate the prevalence of the mutations of deoxyribonucleic acid (DNA) repair genes in tumors using the BROCA panel and to correlate tumor regression with mutations status. (Integrated) II. To evaluate changes in tumor hypoxia on cediranib treatment compared to baseline by \[F-18\] fluoromisonidazole (FMISO) positron emission tomography/computed tomography (PET/CT) in patients with NSCLC.

III. To evaluate levels of angiogenesis/inflammatory markers including VEGF at baseline and on treatment.

IV. To evaluate levels of circulating tumor deoxyribonucleic acid (ctDNA) at baseline and on treatment.

OUTLINE:

Patients receive cediranib maleate orally (PO) once daily (QD) on day 1. Patients undergoing FMISO scan also receive olaparib PO twice daily (BID) beginning the day after the second FMISO scan and the rest of the patients receive olaparib PO BID beginning day 4 of cycle 1. Cycles repeat every 28 days (35 days for cycle 1) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks. Patients who discontinue the study treatment for reasons other than disease progression or withdrawal of consent will continue to be followed every 4 weeks until disease progression, start of new therapy, or death, whichever occurs first.

A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors

In the first 20 endpoint-evaluable patients with non-small cell lung cancer and 20 endpoint-evaluable patients with triple negative breast cancer, the exploratory analyses will be done using Fisher's exact tests, Mann-Whitney U tests or McNemar's test depending on the type of data observed.

Measured by 18F-fluoromisonidazole positron emission tomography/computed tomography scans (non-small cell lung cancer). For the pre- and post-cediranib therapy outcome analysis, paired t- test or Wilcoxon signed-rank test will be applied for the continuous variables.

Will be assessed using paired t- test or Wilcoxon signed-rank.

Measured by Response Evaluation Criteria in Solid Tumors version 1.1. The exact two-sided 95% confidence interval for the objective response rate will be reported.

Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics, including means, standard deviations, and ranges for continuous parameters, as well as percentages and frequencies for categorical parameters, will be presented. Adverse medical events will be tabulated. National Cancer Institute toxicity grade 3 and grade 4 laboratory abnormalities will be listed.

Estimated using the Kaplan-Meier method with the 95% confidence intervals. Thomas and Grunkemeier confidence interval 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.

AstraZeneca

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors	NCT02498613	Advanced Malign... Metastatic Lung... Metastatic Lung... Metastatic Panc... Metastatic Trip... Pancreatic Duct... Stage III Breas... Stage III Lung ... Stage III Lung ... Stage III Pancr... Stage IIIA Brea... Stage IIIA Lung... Stage IIIA Lung... Stage IIIB Brea... Stage IIIB Lung... Stage IIIB Lung... Stage IIIC Brea... Stage IV Breast... Stage IV Lung N... Stage IV Lung S... Stage IV Pancre... Triple-Negative... Unresectable Lu... Unresectable Pa... Unresectable Pa... Unresectable Tr...	18F-Fluoromison... Cediranib Malea... Laboratory Biom... Olaparib Positron Emissi...	18 Years -	National Cancer Institute (NCI)
A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors	NCT02498613	Advanced Malign... Metastatic Lung... Metastatic Lung... Metastatic Panc... Metastatic Trip... Pancreatic Duct... Stage III Breas... Stage III Lung ... Stage III Lung ... Stage III Pancr... Stage IIIA Brea... Stage IIIA Lung... Stage IIIA Lung... Stage IIIB Brea... Stage IIIB Lung... Stage IIIB Lung... Stage IIIC Brea... Stage IV Breast... Stage IV Lung N... Stage IV Lung S... Stage IV Pancre... Triple-Negative... Unresectable Lu... Unresectable Pa... Unresectable Pa... Unresectable Tr...	18F-Fluoromison... Cediranib Malea... Laboratory Biom... Olaparib Positron Emissi...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iii lung small cell carcinoma ajcc v7