Guadecitabine and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT02901899 | Completed Phase 2 Results DMC

• 4 other identifiers: NU 16G03STU00203494P30CA060553NCI-2016-01296
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to look at how patients respond to treatment with guadecitabine and pembrolizumab. The researchers will also be looking at the amount of time it takes for cancer to get worse when participants take the study drugs. All participants will be treated with guadecitabine and pembrolizumab. Guadecitabine interferes with the cancer cells' DNA and can increase the production of certain proteins, making cancer cells more recognizable by the immune system. Pembrolizumab helps your immune system to kill cancer cells. Thus the combination of guadecitabine and pembrolizumab may increase the ability of the immune system to eliminate cancer cells. Researchers want to find out whether the combination of guadecitabine and pembrolizumab is effective in treating ovarian cancer that has not responded to traditional chemotherapy. Participants will keep receiving treatment until their cancer gets worse, they have side effects, or they decide they don't want to receive the treatment anymore. After stopping treatment, the study doctor will watch participants for side effects and follow their condition every 6-12 weeks. The study aims to keep track of participants' medical conditions for the rest of their lives. This helps us look at the long-term effects of the study drugs.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Using RECIST 1.1

  Objective response rate (ORR) is defined as the number of patients who's best response is complete response plus those with partial response. Imaging scans will be assessed using RECIST 1.1 to measure ORR to guadecitabine and pembrolizumab in patients with recurrent platinum resistant Ovarian Cancer. In general the following definitions apply Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Assessed from start of treatment and during treatment for up to 38 cycles where 1 cycle equals 21 days (maximum number of cycles that any patient attempted)

Secondary Outcomes (4)

• Objective Response Rate (ORR) Using Immune Related Response Criteria (irRC)

  Up to 3 years

• Progression Free Survival (PFS)

  Up to 3 years

• Clinical Benefit Rate (CBR)

  Assessed from start of treatment and during treatment for up to 38 cycles where 1 cycle equals 21 days (maximum number of cycles that any patient attempted)

• Incidence of Adverse Events

  Assessed from start of treatment and during treatment for up to 38 cycles and up to 90 days post last dose where 1 cycle equals 21 days (maximum number of cycles that any patient attempted)

Study Arms (1)

Treatment (guadecitabine, pembrolizumab)

EXPERIMENTAL

Patients receive guadecitabine SC on days 1-4 and pembrolizumab IV over 30 minutes on day 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Guadecitabine; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Guadecitabine DRUG

Given SC

Also known as: DNMT inhibitor SGI-110, S110, SGI-110

Treatment (guadecitabine, pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (guadecitabine, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (guadecitabine, pembrolizumab)

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 a histological or cytological evidence/confirmation of recurrent epithelial ovarian cancer, primary peritoneal carcinomatosis, or fallopian tube cancer
• Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within 28 days prior to registration
• Prior therapy allowed:
• At least one and no more than 3 platinum based chemotherapy regimens
• Up to 2 non-platinum, cytotoxic regimen
• There is no limit on use of prior biological therapies (hormonal or targeted therapy)
• NOTE: Prior immunotherapy is not allowed
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG), performance status of 0-1 within 14 days prior to registration
• Demonstrate adequate organ function as defined below; all screening labs to be obtained within 14 days prior to treatment initiation:
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (without transfusion or growth factor support/erythropoietin \[EPO\] dependency)
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases

You may not qualify if:

• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to registration or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• NOTE: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• NOTE: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has had a prior anti-cancer monoclonal antibody (mAb) within 28 days prior to registration or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days registration
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days prior to registration and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent; please contact the principal investigator for further clarification if needed
• Hypersensitivity to pembrolizumab or any of its excipients
• Has a known history of active TB (Bacillus tuberculosis)
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) infection
• Has a known history of hepatitis B and/or hepatitis C infection
• Has known history of, or any evidence of active, non-infectious pneumonitis

Sponsors & Collaborators

• Northwestern University: lead
• Merck Sharp & Dohme LLC: collaborator
• Astex Pharmaceuticals, Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

Location

The University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Northwestern Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

Related Publications (1)

• Chen S, Xie P, Cowan M, Huang H, Cardenas H, Keathley R, Tanner EJ, Fleming GF, Moroney JW, Pant A, Akasha AM, Davuluri RV, Kocherginsky M, Zhang B, Matei D. Epigenetic priming enhances antitumor immunity in platinum-resistant ovarian cancer. J Clin Invest. 2022 Jul 15;132(14):e158800. doi: 10.1172/JCI158800.

  PMID: 35671108 DERIVED

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

guadecitabine; pembrolizumab

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

Results Point of Contact

• Title: Daniela Matei, MD
• Organization: Northwestern University

daniela.matei@northwestern.edu

312.472.4684

Study Officials

• Daniela Matei, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 12, 2016
• First Posted: September 15, 2016
• Study Start: November 11, 2016
• Primary Completion: April 1, 2020
• Study Completion: March 31, 2023
• Last Updated: February 20, 2024
• Results First Posted: May 12, 2021

Record last verified: 2024-02

Locations

US (3)