Pembrolizumab Combined With PLD For Recurrent Platinum Resistant Ovarian, Fallopian Tube Or Peritoneal Cancer

NCT02865811 | Completed Phase 2 Results DMC

• 1 other identifier: 16-257
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is studying the combination of Pegylated Liposomal Doxorubicin (PLD) and Pembrolizumab as a possible treatment for Recurrent Ovarian, Fallopian Tube or Peritoneal Cancer that is resistant to platinum therapy. The following interventions will be used in this study:

• Pegylated liposomal doxorubicin (PLD)
• Pembrolizumab

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Keywords

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate [CBR]

  The primary objective was to determine the CBR (complete response \[CR\] + partial response \[PR\] + stable disease \[SD\] \>/= 24 weeks) of the combination of pembrolizumab and PLD.

  24 Weeks

Secondary Outcomes (5)

• Safety of the Combination of Pembrolizumab/PLD

  24 weeks

• Overall Response Rate [ORR]

  24 months

• Duration of Response [DOR]

  24 Months

• Progression-Free Survival [PFS]

  24 weeks

• Overall Survival

  24 Months

Study Arms (1)

Pembrolizumab in Combination With PLD

EXPERIMENTAL

A safety lead in with 6 patients will be studied prior the start of the treatment. * If 2 out of the first 6 patients develop a dose limiting toxicity (DLT), the dose of PLD will be reduced. * If no more than 1 patient of the first 6 patients has evidence of dose limiting toxicities, the dose level will be considered the maximum tolerated dose (MTD) * Pegylated Liposomal Doxorubicin (PLD) pre-determine dosage will be administered every 4 weeks via IV * Pembrolizumab will be administered as a 30 min IV infusion every 3 weeks at a pre-determine dosage

Drug: Pembrolizumab; Drug: Pegylated Liposomal Doxorubicin (PLD)

Interventions

Pembrolizumab DRUG

Please see "Arms" for description.

Also known as: Keytruda

Pembrolizumab in Combination With PLD

Pegylated Liposomal Doxorubicin (PLD) DRUG

Please see "Arms" for description.

Pembrolizumab in Combination With PLD

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1 criteria.
• Have a histologically confirmed diagnosis of epithelial ovarian cancer, fallopian tube or peritoneal cancer. All histologies of epithelial ovarian cancer are eligible except for carcinosarcomas.
• Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab) or extended therapy administered after surgical or non-surgical assessment.
• Patients must have platinum resistant cancer with a platinum free interval of \< 6 months. Progression after last platinum is based on investigator assessment.
• Patients are allowed to receive, but are not required to receive, up to two additional cytotoxic regimens for management of recurrent or persistent disease, with no more than 1 non-platinum, non-taxane regimen.
• Patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy as part of their primary treatment regimen. For the purposes of this study, Poly (ADP-ribose) polymerase (PARP) inhibitors will be considered "cytotoxic." Patients are allowed to receive, but are not required to receive, PARP inhibitors for management of primary or recurrent/persistent disease (either alone or in combination with cytotoxic chemotherapy). Single agent hormonal therapies will not be counted as a line of treatment.
• Have adequate tissue from an archived specimen of ovarian cancer (between 10 to 15 slides of unstained tumor).
• Have a performance status of 0 or 1 on the ECOG Performance Scale (Appendix A).
• Demonstrate adequate organ function as defined in Table 1, all screening labs must be performed within 10 days of treatment initiation.
• Table 1 Adequate Organ Function Laboratory Values
• System Laboratory Value
• Hematological
• Absolute neutrophil count (ANC) ≥1,500 /mcL

You may not qualify if:

• 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 4 weeks of the first dose of treatment.
• 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.
• Patients cannot have primary platinum refractory cancer, i.e. documented cancer progression while receiving platinum or within one month of receipt of a platinum based regimen.
• Has received a prior anthracycline chemotherapy either for ovarian cancer treatment or another previous malignancy.
• Left ventricular ejection fraction (LVEF) defined by multigated acquisition (MUGA) or echocardiogram which is below the institutional lower limit of normal prior to starting study treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients and/or liposomal doxorubicin.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Participants with \< Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If participant underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. In addition, patients cannot have been diagnosed with another malignancy within 3 years of starting 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. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment 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 clinically active and significant 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Northwell Hospital Monter Cancer Center

Lake Success, New York, 11042, United States

Location

Related Publications (1)

• Lee EK, Xiong N, Cheng SC, Barry WT, Penson RT, Konstantinopoulos PA, Hoffman MA, Horowitz N, Dizon DS, Stover EH, Wright AA, Campos SM, Krasner C, Morrissey S, Whalen C, Quinn R, Matulonis UA, Liu JF. Combined pembrolizumab and pegylated liposomal doxorubicin in platinum resistant ovarian cancer: A phase 2 clinical trial. Gynecol Oncol. 2020 Oct;159(1):72-78. doi: 10.1016/j.ygyno.2020.07.028. Epub 2020 Aug 6.

  PMID: 32771276 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

pembrolizumab; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; 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; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Results Point of Contact

• Title: Dr. Ursula Matulonis
• Organization: Dana-Farber Cancer Institute

ursula_matulonis@dfci.harvard.edu

617-632-2334

Study Officials

• Ursula Matulonis, MD

  Dana-Farber Cancer Institute

  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: MD

Study Record Dates

• First Submitted: August 10, 2016
• First Posted: August 12, 2016
• Study Start: September 15, 2016
• Primary Completion: August 1, 2020
• Study Completion: March 1, 2022
• Last Updated: September 13, 2022
• Results First Posted: August 3, 2021

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)