Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Adavosertib With or Without Olaparib in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03579316
Recruitment Status : Recruiting
First Posted : July 6, 2018
Last Update Posted : October 18, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies how well adavosertib with or without olaparib work in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent). Adavosertib and olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Drug: Adavosertib Drug: Olaparib Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine the objective response rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) of adavosertib (AZD1775) alone or in combination with olaparib in women with recurrent ovarian cancer in whom progression has been documented following poly ADP-ribose polymerase (PARP) inhibitor therapy.

SECONDARY OBJECTIVES:

I. To evaluate the overall safety and tolerability of AZD1775 alone or in combination with olaparib in this population.

II. To evaluate the disease control rate (DCR) = overall response rate (ORR) plus stable disease rate for 16 weeks.

III. To evaluate the progression free survival (PFS) and overall survival (OS) of this population following AZD1775 alone or in combination with olaparib.

IV. To evaluate the duration of response by RECIST version (v)1.1.

EXPLORATORY OBJECTIVES:

I. To evaluate the efficacy of each arm by BRCA-mutation status (BRCA-mt) and homologous recombination deoxyribonucleic acid (DNA) repair deficiencies (HRD).

II. To describe endogenous and dynamic markers of DNA damage response in tumor tissue and circulating surrogates, such as circulating tumor cells (CTC), circulating tumor DNA (ctDNA), exosomes (cellular/nuclear), cell cycle kinetics (CDKs), and immunophenotype.

III. To examine genomic alterations associated with response and mechanisms of resistance to olaparib and/or AZD1775.

OUTLINE: Patients are randomized to 1 of 2 arms. If enrollment pauses for 1 arm, patients will be assigned to the enrolling arm.

ARM I: Patients receive adavosertib orally (PO) once daily (QD) on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive olaparib PO twice daily (BID) on days 1-21 and adavosertib PO QD on days 1-3 and 8-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized 2-Arm, Non-Comparative Phase 2 Study of AZD1775 Alone or AZD1775 and Olaparib in Ovarian Cancer Patients Who Have Progressed During PARP Inhibition
Actual Study Start Date : December 7, 2018
Estimated Primary Completion Date : October 30, 2022
Estimated Study Completion Date : October 30, 2023


Arm Intervention/treatment
Active Comparator: Arm I (adavosertib)
Patients receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Adavosertib
Given PO
Other Names:
  • AZD-1775
  • AZD1775
  • MK-1775
  • MK1775

Experimental: Arm II (olaparib, adavosertib)
Patients receive olaparib PO BID on days 1-21 and adavosertib PO QD on days 1-3 and 8-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Adavosertib
Given PO
Other Names:
  • AZD-1775
  • AZD1775
  • MK-1775
  • MK1775

Drug: Olaparib
Given PO
Other Names:
  • AZD 2281
  • AZD-2281
  • AZD2281
  • KU-0059436
  • Lynparza
  • PARP Inhibitor AZD2281




Primary Outcome Measures :
  1. Objective response rate defined as complete response (CR) or partial response (PR), assessed by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 6 months ]
    Will be computed and presented along with an exact 90% confidence interval using the method of Clopper and Pearson.


Secondary Outcome Measures :
  1. Disease control rate defined as the percentage of patients with a confirmed best overall response of complete response or partial response, or a best overall response of stable disease [ Time Frame: Up to 6 months ]
    The point estimate per treatment arm and the 95% Pearson-Clopper confidence interval for the objective response rates will be provided. Logistic regression analyses will be performed to assess the influence of baseline covariates in an exploratory manner.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has read and understands the informed consent form and has given written informed consent prior to any study procedures.
  • Histologically confirmed recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer for which there is no known or established treatment available with curative intent.
  • Have demonstrated progressive disease while taking a PARP inhibitor as a previous therapy or within 6 months of completing PARP inhibitor therapy. Response to prior PARP inhibitor(i) is not required.
  • Prior PARP therapy could have been administered as either treatment for recurrent disease or as maintenance following prior treatment.
  • Measurable disease according to RECIST v1.1.
  • Adequate archived primary or metastatic tumor tissue collected before the prior PARP therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1.
  • Absolute neutrophil count (ANC) >=1500/L (within 14 days of study drug[s] initiation).
  • Hemoglobin (Hgb) >= 10 g/dL with no blood transfusion in the past 14 days (within 14 days of study drug[s] initiation).
  • Platelets >= 100,000/L (within 14 days of study drug[s] initiation).
  • Alanine transaminase (ALT) and aspartate transaminase (AST) =< 2.5 x upper limit of normal (ULN) or =< 5 x ULN if known hepatic metastases (within 14 days of study drug[s] initiation).
  • Serum bilirubin within normal limits (WNL) or =< 1.5 x ULN in patients with liver metastases; or total bilirubin =< 3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's syndrome (within 14 days of study drug[s] initiation).
  • Patients should have calculated or measured creatinine clearance of >= 50 mL/min.
  • Women who are not of child-bearing potential and fertile females of childbearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum pregnancy test within 3 days prior to the start of study treatment.
  • Predicted life expectancy >= 16 weeks.
  • Willingness and ability to comply with study and follow-up procedures.

Exclusion Criteria:

  • Prior Treatment:

    • PARP inhibitor: Most oral PARP inhibitors (the immediate prior therapy) have a half-life for which 5 half-lives is =< 21 days. Thus, a minimum of 10 days between termination of the prior treatment and administration of olaparib and/or AZD1775 treatment is required. In the event a PARP inhibitor has a longer half-life where 5 half-lives is >= 21 days, treatment of olaparib and/or AZD1775 should not begin for 5 half-lives or at least 21 days, whichever is shorter.
    • Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration (study enrollment). Continuation of hormone replacement therapy is permitted.
    • Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to first dose of study drug (6 weeks for nitrosoureas or mitomycin C).
  • Major surgical procedures =< 28 days of beginning study treatment, or minor surgical procedures =< 7 days. No waiting period required following port-a-cath placement.
  • Grade > 1 toxicity from prior therapy (except alopecia or anorexia).
  • Patient has an inability to swallow oral medications and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN).
  • Known central nervous system (CNS) disease other than neurologically stable, treated brain metastases - defined as metastasis having no evidence of progression or hemorrhage for at least 3 weeks after treatment (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrollment.
  • Patient has had a prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to day -3 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug. Co-administration of aprepitant or fosaprepitant during this study is prohibited.
  • Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to: St. John's wort, kava, ephedra (mahung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng. Patients should stop using these herbal medications 7 days prior to first dose of study treatment.
  • Any known hypersensitivity or contraindication to the components of the study drug AZD1775 or olaparib.
  • Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) >= class 2. a. Unstable angina pectoris; b. Congestive heart failure; c. Acute myocardial infarction; d. Conduction abnormality not controlled with pacemaker or medication; e. Significant ventricular or supraventricular arrhythmias (patients with chronic rate- controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
  • AZD1775 should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. AZD1775 has not been studied in patients with ventricular arrhythmias or recent myocardial infarction.
  • Patients with resting corrected QT interval (specifically QTc calculated using the Fridericia formula [QTcF]) > 470 msec from a single electrocardiogram (ECG) performed at study entry or congenital long QT syndrome.
  • Pregnant or breast-feeding.
  • Serious active infection at the time of study entry, or another serious underlying medical condition that would impair the ability of the patient to receive study treatment.
  • Presence of other active invasive cancers.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with protocol.
  • Patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03579316


Contacts
Layout table for location contacts
Contact: Robert Coleman 713-745-3357 rcoleman@mdanderson.org

Locations
Layout table for location information
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Joyce F. Liu       joyce_liu@dfci.harvard.edu   
Principal Investigator: Joyce F. Liu         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Robert L. Coleman    713-745-3357      
Principal Investigator: Robert L. Coleman         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Robert L Coleman M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03579316     History of Changes
Other Study ID Numbers: 2016-0677
NCI-2018-01105 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0677 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: July 6, 2018    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Olaparib
MK-1775
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents