Pembrolizumab, Paclitaxel, and Carboplatin in Patients With Advanced Stage Epithelial Ovarian Cancer (EOC).

NCT02834975 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 20160477
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that tumor cell killing by cytotoxic chemotherapy exposes the immune system to high levels of tumor antigens.The combination of Paclitaxel/Carboplatin and Pembrolizumab may result in deeper and more durable responses compared with standard chemotherapy alone.

Conditions

Fallopian Tube Cancer; Peritoneum Cancer; Epithelial Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Objective Response Rate (pORR) in Participants Receiving Protocol Therapy

  The pORR will be calculated as the percentage of participants with pathologic complete response (pCR) and pathologic partial response (pPR) overall as best response. For this protocol, pathologic complete response (pCR) will be defined as no residual macroscopic or (viable) microscopic disease. Pathologic partial response (pPR) will be defined as the presence of residual (viable) microscopic tumor, and the size of the largest focus will be provided for possible outcome correlation.

  Up to 48 months

Secondary Outcomes (2)

• Progression-Free Survival (PFS)

  Up to 48 months

• Number of Participants Experiencing Treatment-related Toxicity

  Up to 48 Months

Study Arms (1)

Pembrolizumab, Paclitaxel + Carboplatin

EXPERIMENTAL

The following therapy will be administered during each 21-day cycle for a maximum of eight (8) cycles: * Pembrolizumab 200mg intravenously (IV); * Paclitaxel 175 mg/m2 IV in a neoadjuvant setting (NACT); * Paclitaxel same as NACT, OR 80 mg/m2 IV dose dense option in an adjuvant setting (ACT); * Carboplatin IV area under the curve (AUC) of 6.

Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Pembrolizumab DRUG

Pembrolizumab on Day 1 of each cycle.

Also known as: Keytruda, MK-3475

Pembrolizumab, Paclitaxel + Carboplatin

Paclitaxel DRUG

* NACT: Paclitaxel on Day 1 of each cycle; * ACT: Paclitaxel same as NACT OR; dose-dense option weekly per protocol.

Also known as: Taxol

Pembrolizumab, Paclitaxel + Carboplatin

Carboplatin DRUG

Carboplatin IV on Day 1 of each cycle.

Pembrolizumab, Paclitaxel + Carboplatin

Eligibility Criteria

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

You may qualify if:

• No prior treatment for primary advanced (Stage III or IV) high grade epithelial ovarian, primary peritoneal, or fallopian tube carcinoma such as irradiation, chemotherapy, hormonal therapy, immunotherapy, investigational therapy, and/or other concurrent agents or therapies.
• Patients must undergo diagnostic laparoscopy for disease assessment for tissue biopsies to confirm diagnosis with planned interval tumor reductive surgery after completion of 3-4 cycles of treatment. For those not medically fit to undergo laparoscopy, as determined by the Investigator. (interventional radiology) IR-guided core biopsies may be used.
• Patients must be appropriate candidates for planned neoadjuvant chemotherapy (NACT) with combination carboplatin and paclitaxel given intravenously (IV) every 3 weeks ( IV Q3W).
• Tissue from an archival sample or newly obtained core or excisional biopsy of a tumor lesion.
• Age ≥ 18 years.
• Life expectancy \> 3 months.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Patients must have normal organ and marrow function as defined below:
• Hematologic
• Absolute neutrophil count (ANC) ≥1,500 /microliter (mcL).
• Platelets ≥ 100,000 / mcL.
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or Erythropoietin (EPO) dependency
• Renal
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR
• Measured or calculated a creatinine clearance ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl). Creatinine clearance should be calculated per institutional standard.

You may not qualify if:

• Patients who are currently in or have participated in a study of an investigational agent or used an investigational device within 4 weeks of the first dose of treatment.
• Histology showing mucinous or low grade epithelial ovarian cancer.
• Patients who will not be likely to undergo IDS either secondary to performance status or sites of disease. If at the time of surgery, the patient is deemed to be surgically resectable to no gross residual, the patient will not be eligible for the study.
• Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study 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 28 days prior to study treatment.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has received prior therapy with an anti-PD1, anti-PDL1, anti-CD137, anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) or anti-PDL2 agent.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• 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 study treatment.
• Prior monoclonal antibody 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.
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to previously administered event. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for this study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has active autoimmune disease that has required systemic treatment in the past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment.
• Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.

Sponsors & Collaborators

• University of Miami: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

pembrolizumab; Paclitaxel; Carboplatin

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; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Abdulrahman Sinno, MD
• Organization: University of Miami

ak.sinno@med.miami.edu

+1 (305) 2432233

Study Officials

• Marilyn Huang, MD, MS

  University of Miami

  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: Associate Professor of Clinical

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: July 15, 2016
• Study Start: December 22, 2016
• Primary Completion: September 1, 2022
• Study Completion: December 1, 2022
• Last Updated: November 7, 2023
• Results First Posted: November 7, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)