Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT02101775 | Active Not Recruiting Phase 2 Results

• 10 other identifiers: NCI-2014-00620PHL-093NCI 95689568N01CM00032N01CM00038N01CM00071U10CA180821UM1CA186644UM1CA186705
• Study Type: interventional
• Target: 124
• Locations: 3 countries
• Sites: 16

Brief Summary

This randomized phase II clinical trial studies how well gemcitabine hydrochloride and WEE1 inhibitor MK-1775 work compared to gemcitabine hydrochloride alone in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of time. Gemcitabine hydrochloride may prevent tumor cells from multiplying by damaging their deoxyribonucleic acid (DNA, molecules that contain instructions for the proper development and functioning of cells), which in turn stops the tumor from growing. The protein WEE1 may help to repair the damaged tumor cells, so the tumor continues to grow. WEE1 inhibitor MK-1775 may block the WEE1 protein activity and may increase the effectiveness of gemcitabine hydrochloride by preventing the WEE1 protein from repairing damaged tumor cells without causing harm to normal cells. It is not yet known whether gemcitabine hydrochloride with or without WEE1 inhibitor MK-1775 may be an effective treatment for recurrent ovarian, primary peritoneal, or fallopian tube cancer.

Conditions

Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Malignant Mixed Mesodermal (Mullerian) Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Ovarian Undifferentiated Carcinoma; Ovarian Brenner Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  To evaluate the progression free survival (PFS) of subjects with recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer receiving gemcitabine in combination with AZD1775 compared to subjects receiving gemcitabine in combination with placebo. Progression is defined, using the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guideline, as at least a 20% increase in the sum of the diameters of target lesions or the appearance of one or more new lesions.

  From start of treatment until date of progression or death, whichever occurs first, up to 1 year follow-up

Secondary Outcomes (6)

• Objective Response

  From start of treatment, every 6-8 weeks, until time of progression or death, whichever occurs first, up to 1 year follow-up

• Response According to CA125 Criteria

  From start of treatment, every 4 weeks, until time of progression or death, whichever occurs first, up to 1 year follow-up

• Overall Survival

  From start of study treatment, every 12 weeks, until death, up to 22 months follow-up

• Number of Participants With Grade 3 or 4 Adverse Events Related to Study Treatment

  From start of treatment until AE resolution, stabilization, or improvement to less than grade 2, up to 1 year follow-up

• TP53 Mutations

  Baseline

Other Outcomes (7)

• Patient Reported Outcomes

  First 3 months

• TP53 Mutations in Circulating Tumor Deoxyribonucleic Acid

  Baseline

• Change in Levels of Circulating Deoxyribonucleic Acid TP53 Mutations by TAm-Seq

  Baseline to up to 1 year

Study Arms (2)

Arm I (WEE1 inhibitor MK-1775, gemcitabine hydrochloride)

EXPERIMENTAL

Patients receive WEE1 inhibitor MK-1775 PO on days 1, 2, 8, 9, 15, and 16 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Adavosertib; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Questionnaire Administration

Arm II (placebo, gemcitabine hydrochloride)

ACTIVE COMPARATOR

Patients receive placebo PO on days 1, 2, 8, 9, 15, and 16 and gemcitabine hydrochloride as patients in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo Administration; Other: Questionnaire Administration

Interventions

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar, LY 188011, LY-188011, LY188011

Arm I (WEE1 inhibitor MK-1775, gemcitabine hydrochloride); Arm II (placebo, gemcitabine hydrochloride)

Adavosertib DRUG

Given PO

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

Arm I (WEE1 inhibitor MK-1775, gemcitabine hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (WEE1 inhibitor MK-1775, gemcitabine hydrochloride); Arm II (placebo, gemcitabine hydrochloride)

Pharmacological Study OTHER

Correlative studies

Arm I (WEE1 inhibitor MK-1775, gemcitabine hydrochloride); Arm II (placebo, gemcitabine hydrochloride)

Placebo Administration OTHER

Given PO

Arm II (placebo, gemcitabine hydrochloride)

Questionnaire Administration OTHER

Ancillary studies

Arm I (WEE1 inhibitor MK-1775, gemcitabine hydrochloride); Arm II (placebo, gemcitabine hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed epithelial ovarian, primary peritoneal and fallopian tube carcinoma; all histologic subtypes of epithelial ovarian cancer are eligible, but only patients with high grade serous ovarian cancer will be considered for the statistical analysis; non-high grade serous cancers will be allowed in an exploratory cohort
• Patients must be platinum-resistant (platinum-free interval \< 6 months) or have platinum-refractory disease as per Gynecologic Cancer Intergroup Committee (GCIC) criteria; disease progression has to be radiologic or clinical; biomarker progression with CA125 after a platinum based regimen would not be sufficient evidence of disease progression; the patients must have had radiological progression to that regimen
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \> 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• There is no limitation in the number of prior lines of therapy
• Patients must have completed any prior chemotherapy, radiotherapy or major surgery at least 4 weeks before receiving study treatment; ongoing toxicities related to treatment must be =\< grade 1 and patients with grade 2 alopecia or peripheral neuropathy can also be included; palliative radiation to \< 10% of bone marrow is permissible if completed within one week of commencing study treatment as long as the toxicities secondary to palliative radiotherapy are limited to grade 1; the lesions that have received radiation treatment immediately before will be excluded as target lesions; previously irradiated lesions can be considered as targeted lesions, as long as there is prove of radiological progression
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 3 months
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 90 g/L
• Blood transfusions are allowed at any time during the screening, treatment or follow-up period, according to the center recommendations
• Prothrombin time (PT), partial thromboplastin time (PTT) and international normalized ratio (INR) =\< 1.5 upper limit of normal (ULN)
• Total bilirubin =\< 1.5 x institutional upper limit of normal; unless due to Gilbert's syndrome
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal (5 x if liver metastases)

You may not qualify if:

• Patients who previously received gemcitabine for the treatment of recurrent disease
• Patients who are receiving any other investigational agents
• Patients with clinically or radiologically unstable brain metastases are excluded from this clinical trial
• Note: patients with stable brain metastases after treatment, for at least 3 months prior to enrolling on this trial, could participate in the study; patients should be off, or on a stable dose of steroids
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD 1775 (MK-1775) or gemcitabine
• Patients taking the following prescription or non-prescription drugs or other products (i.e. grapefruit juice) are ineligible: sensitive cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) substrates, CYP3A4 substrates with a narrow therapeutic index, moderate to potent inhibitors/inducers of CYP3A4; patients would be eligible if the medications can be discontinued two weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication
• Pregnant and breastfeeding women are excluded from this study
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Uncontrolled intercurrent illness including, but not limited to, myocardial infarction within 6 months, congestive heart failure, symptomatic congestive heart failure, unstable angina pectoris, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, active liver disease or cerebrovascular disease with previous stroke, or psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (16)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

BCCA-Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Ottawa Hospital and Cancer Center-General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network Princess Margaret Cancer Center P2C

Toronto, Ontario, M5G 2M9, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM - Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

Location

National University Hospital Singapore

Singapore, 119074, Singapore

Location

Related Publications (1)

• Lheureux S, Cristea MC, Bruce JP, Garg S, Cabanero M, Mantia-Smaldone G, Olawaiye AB, Ellard SL, Weberpals JI, Wahner Hendrickson AE, Fleming GF, Welch S, Dhani NC, Stockley T, Rath P, Karakasis K, Jones GN, Jenkins S, Rodriguez-Canales J, Tracy M, Tan Q, Bowering V, Udagani S, Wang L, Kunos CA, Chen E, Pugh TJ, Oza AM. Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021 Jan 23;397(10271):281-292. doi: 10.1016/S0140-6736(20)32554-X.

  PMID: 33485453 DERIVED

MeSH Terms

Conditions

Brenner Tumor; Neoplasms; Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

adavosertib; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Fibroepithelial; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Neoplasms by Site; Fallopian Tube Diseases; Endocrine Gland Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

* Randomization in a 2:1 ratio is associated with reduced statistical power - increased the sample size by 12% compared to a 1:1 randomization design * No stratification factors because of the small sample size, potentially resulting in imbalances in BRCA mutation status * Absence of quality-of-life assessment

Results Point of Contact

• Title: Dr. Amit Oza
• Organization: University Health Network - Princess Margaret Cancer Centre

Amit.Oza@uhn.ca

416-946-4501

Study Officials

• Amit M Oza

  University Health Network-Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 2, 2014
• Study Start: July 21, 2014
• Primary Completion: February 3, 2022
• Study Completion (Estimated): March 6, 2027
• Last Updated: April 13, 2026
• Results First Posted: September 8, 2023

Record last verified: 2026-03

Locations

US (8); SG (1); CA (7)