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

NCT03579316 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2016-0677NCI-2018-01105
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 2

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.

Conditions

Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Will be defined as complete response (CR) or partial response (PR), assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Will be computed and presented along with an exact 90% confidence interval using the method of Clopper and Pearson.

  Up to 6 months

Secondary Outcomes (1)

• Disease control rate

  Up to 6 months

Study Arms (3)

Arm I (adavosertib)

ACTIVE COMPARATOR

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

Arm II (olaparib, adavosertib)

EXPERIMENTAL

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; Drug: Olaparib

Arm III (ceralasertib, olaparib)

EXPERIMENTAL

Patient receive ceralasertib tablets by PO BID each day on Days 1-14. You will also take olaparib tablets by PO BID each day on Days 1-28.

Drug: Olaparib; Drug: Ceralasertib

Interventions

Adavosertib DRUG

Given PO

Also known as: AZD-1775, AZD1775, MK-1775, MK1775

Arm I (adavosertib); Arm II (olaparib, adavosertib)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Arm II (olaparib, adavosertib); Arm III (ceralasertib, olaparib)

Ceralasertib DRUG

Given PO

Also known as: AZD6738

Arm III (ceralasertib, olaparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has read and understands the informed consent form (ICF) 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 licensed PARP inhibitor as a previous therapy or within 6 months of completing PARP inhibitor therapy. Response to prior PARPi is not required. However, there must be documented evidence of progression prior to study entry.
• Prior PARP therapy could have been administered as either treatment for recurrent disease or as maintenance following prior treatment.
• At least one measurable lesion 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 within 28 days of study entry.
• Patients must have adequate organ and bone marrow function measured within 14 days of study drug(s) initiation:
• Absolute neutrophil count (ANC) ≥1500/μL
• Hemoglobin (Hgb) ≥10 g/dL with no blood transfusion in the past 28 days
• Platelets ≥100,000/μL with no platelet transfusion in the past 28 days
• Alanine Transaminase (ALT) and Aspartate Transaminase (AST) ≤2.5 x upper limit of normal (ULN) or ≤5 x ULN if known hepatic metastases.
• 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.
• Patients must have creatinine clearance (CrCl) of ≥51 mL/min estimated or measured using standard methodology at the investigating centre (i.e. Cockcroft- Gault, or 24 hr urine):
• Estimated CrCl = (140-age \[years\]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72 a where F=0.85 for females and F=1 for males

You may not qualify if:

• 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 are ≥ 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 any systemic immunologic agents, must be discontinued at least three weeks prior to first dose of study drug (6 weeks for nitrosoureas or mitomycin C).
• Cytotoxic chemotherapy, hormonal or non-hormonal targeted therapy within 21 days of Cycle 1 Day 1 is not permitted (a duration of 30 days or 5 half-lives (whichever is shorter) is required for patients treated with non-cytotoxic drugs). The minimum washout period for immunotherapy is 42 days. Palliative radiotherapy must have been completed 21or more days before Cycle 1 Day 1 (with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study treatment). The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 5 days prior to the study treatment. Receiving, or having received during the 14 days prior to first dose, corticosteroids (at a dose \> 10 mg prednisone/day or equivalent) for any reason.
• 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). Patient has refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection, with clinically significant sequelae that would preclude adequate absorption of the study medication.
• Patients with symptomatic uncontrolled brain metastases. Patients with a history of treated central nervous system (CNS) metastases are eligible provided they meet all of the following criteria: disease outside the CNS is present, no clinical evidence of progression since completion of CNS-directed therapy, minimum 3 weeks between completion of radiotherapy and Cycle 1 Day 1 and recovery from significant (Grade ≥ 3) acute toxicity with no ongoing requirement for \>10 mg of prednisolone per day or an equivalent dose of other corticosteroid. If on corticosteroids, the patient should be receiving a stable dose of corticosteroids, started at least 4 weeks prior to treatment.
• 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 (see Appendix G).
• The use of herbal supplements or 'folk remedies' (and medications and foods that significantly modulate CYP3A activity) should be discouraged. 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 herbal medications 7 days prior to first dose of study treatment. If deemed necessary, such products may be administered with caution and the reason for use documented in the CRF.
• Any known hypersensitivity or contraindication to the components of the study drugs AZD1775, ceralasertib 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 (see Appendix F).
• Unstable angina pectoris
• Congestive heart failure

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

adavosertib; olaparib; ceralasertib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Shannon Westin

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2018
• First Posted: July 6, 2018
• Study Start: December 7, 2018
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

US (2)