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Durvalumab and Tremelimumab in Treating Participants With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

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ClinicalTrials.gov Identifier: NCT03026062
Recruitment Status : Recruiting
First Posted : January 20, 2017
Last Update Posted : January 15, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies how well durvalumab and tremelimumab work in treating participants with ovarian, primary peritoneal, or fallopian tube cancer that has come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether give durvalumab and tremelimumab in combination or sequential administration works better in treating participants with ovarian, primary peritoneal, or fallopian tube cancer.

Condition or disease Intervention/treatment Phase
Platinum-Resistant Fallopian Tube Carcinoma Platinum-Resistant Ovarian Carcinoma Platinum-Resistant Primary Peritoneal Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Refractory Fallopian Tube Carcinoma Refractory Ovarian Carcinoma Refractory Primary Peritoneal Carcinoma Biological: Durvalumab Biological: Tremelimumab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the median immune-related progression-free survival (irPFS) in the experimental arms.

SECONDARY OBJECTIVES:

I. To determine the rate of grade III or higher treatment related toxicity in each experimental arm.

II. To describe the immunological and gene expression changes induced by tremelimumab and the combination of tremelimumab and durvalumab in epithelial ovarian cancer (EOC) tumor tissues and blood.

III. To determine the median overall survival (OS), objective response rate (ORR), and irPFS rate at 10 months.

IV. To determine the proportion of patients that discontinue treatment due to side effects.

EXPLORATORY OBJECTIVES:

I. To determine second progression-free survival (PFS) (PFS2) following initial progression in each arm.

II. To determine the response rate to durvalumab (MEDI4736) following treatment with tremelimumab (in the sequential arm).

III. To evaluate the patient reported symptom burden in each experimental arm.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I (SEQUENTIAL): Participants receive tremelimumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Participants then receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

ARM II (COMBINATION): Participants receive tremelimumab IV and durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Participants then receive durvalumab IV on day 1. Treatment repeats every 4 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

After study treatment, participants are followed up at 30 days and then every 2 months thereafter.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab Administered in Combination Versus Sequentially in Recurrent Platinum-Resistant Epithelial Ovarian Cancer
Actual Study Start Date : May 18, 2017
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2022


Arm Intervention/treatment
Experimental: Arm I (sequential tremelimumab, durvalumab)
Participants receive tremelimumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Participants then receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
Biological: Durvalumab
Given IV
Other Names:
  • Imfinzi
  • Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
  • MEDI-4736
  • MEDI4736

Biological: Tremelimumab
Given IV
Other Names:
  • Anti-CTLA4 Human Monoclonal Antibody CP-675,206
  • CP-675
  • CP-675,206
  • CP-675206
  • Ticilimumab

Experimental: Arm II (combination tremelimumab, durvalumab)
Participants receive tremelimumab IV and durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Participants then receive durvalumab IV on day 1. Treatment repeats every 4 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
Biological: Durvalumab
Given IV
Other Names:
  • Imfinzi
  • Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
  • MEDI-4736
  • MEDI4736

Biological: Tremelimumab
Given IV
Other Names:
  • Anti-CTLA4 Human Monoclonal Antibody CP-675,206
  • CP-675
  • CP-675,206
  • CP-675206
  • Ticilimumab




Primary Outcome Measures :
  1. Immune-related progression-free survival (irPFS) [ Time Frame: Up to 4 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
  2. Age >/= 18 years at time of study entry.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  4. Adequate normal organ and marrow function as defined by: Hemoglobin >/= 9.0 g/dL (transfusion is allowed to correct anemia); Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L (> 1500 per mm^3); Platelet count >/= 100 x 10^9/L (>100,000 per mm^3); Serum bilirubin </= 1.5 x institutional upper limit of normal (ULN) unless diagnosed with Gilbert's syndrome; AST and ALT </= 2.5 x ULN unless liver metastases are present, in which case it must be </= 5x ULN; Serum creatinine CL >40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance: Creatinine CL (mL/min) = [Weight (kg) x (140 - Age) x 0.85]/[72 x serum creatinine (mg/dL)].
  5. Subjects must either be of non-reproductive potential (i.e., post-menopausal by history: >/= 60 years old and no menses for >/= 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
  6. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including biopsies and follow up.
  7. Histology (reviewed at MDACC) showing recurrent high grade epithelial ovarian, peritoneal, or fallopian tube cancer.
  8. Platinum resistant or refractory disease as defined by progression of disease on a platinum-containing regimen or recurrence of disease within 180 days of previous platinum treatment.
  9. Have measurable disease based on modified RECIST 1.1. For the purposes of this study measurable disease is defined at least one "target" lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each target lesion must be >20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or >10 mm when measured by spiral CT. The target lesion must be distinct from other tumor areas selected for pre-treatment biopsies. Pre-treatment imaging must be performed within 4 weeks of starting therapy.

Exclusion Criteria:

  1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  2. Previous enrollment or randomization in the present study.
  3. Participation in another clinical study with an investigational product administered during the last 28 days.
  4. Any previous treatment with adoptive T cells therapy, a PD1 or PDL1 inhibitor, including Durvalumab or any anti-CTLA4 therapy, including Tremelimumab.
  5. History of another primary malignancy except for: malignancy treated with curative intent and with no known active disease >/= 5 years before the first dose of study drug and of low potential risk for recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; or adequately treated carcinoma in situ without evidence of disease, e.g., cervical cancer in situ.
  6. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) </= 28 days prior to the first dose of study drug (</= 21 days prior to the first dose of study drug for subjects who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and </= 6 weeks for nitrosourea, mitomycin C, or bevacizumab). (If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required.)
  7. Mean QT interval corrected for heart rate (QTc) >/= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
  8. Current or prior use of immunosuppressive medication within 28 days before the first dose of Durvalumab OR Tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroid premedication for the prevention of radiologic contrast hypersensitivity is allowed.
  9. Any unresolved toxicity (> CTCAE grade 1) from previous anti-cancer therapy, excluding alopecia. Subjects with irreversible toxicity greater than grade 1 that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
  10. Any prior Grade >/= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > Grade 1.
  11. Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
  12. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
  13. History of primary immunodeficiency.
  14. History of allogeneic organ transplant.
  15. History of hypersensitivity to Durvalumab, Tremelimumab, or any excipient.
  16. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
  17. Known history of previous clinical diagnosis of tuberculosis.
  18. History of leptomeningeal carcinomatosis or brain metastasis.
  19. Unresolved partial or complete small or large bowel obstruction.
  20. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving Durvalumab OR Tremelimumab.
  21. Subjects who are pregnant, breast-feeding or of reproductive potential who are not employing an effective method of birth control or are not willing to employ effective birth control from screening to 180 days after the last dose of Durvalumab + Tremelimumab combination therapy or 90 days after the last dose of Durvalumab monotherapy, whichever is the longer time period.
  22. Any medical, social, or psychological condition that would interfere with evaluation of study treatment or interpretation of patient safety or study results.
  23. Subjects with uncontrolled seizures.
  24. Non-English speakers will be excluded from participating in the patient-reported outcomes component of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03026062


Contacts
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Contact: Ljiljana A. Miljevic (713) 792-8578 lmilojev@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Amir A. Jazaeri    713-745-1613      
Principal Investigator: Amir A. Jazaeri         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Amir A Jazaeri M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03026062    
Other Study ID Numbers: 2016-0093
NCI-2018-01240 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0093 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: January 20, 2017    Key Record Dates
Last Update Posted: January 15, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Durvalumab
Ipilimumab
Tremelimumab
Antibodies, Monoclonal
Immunoglobulins
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents