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Clinical Trial 20175

Cancer Type: Gynecological Tumor
Study Type: Treatment
NCT#: NCT03894215

Phase: Phase II
Prinicipal Investigator:

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Overview

Study Title

A Two-arm, Randomized, Non-comparative, Phase 2 Trial of AGEN2034 (anti-PD-1) as a Monotherapy or Combination Therapy with AGEN1884 (anti-CTLA4) or with Placebo in Women with Recurrent Cervical Cancer (Second Line) - RaPiDS

Summary

This is a randomized, blinded, non-comparative, two-arm Phase 2 clinical trial to assess the efficacy and safety of AGEN2034 administered with placebo (Treatment Arm 1 - monotherapy) or with AGEN1884 (Treatment Arm 2 - combination therapy) for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first-line platinum-based chemotherapy. The study is not intended to compare the efficacy of the 2 experimental arms. Rather, the efficacy of each arm will be evaluated against its relevant historical controls as appropriate.

Objective

Primary Objective: To assess the Objective Response Rate(ORR) to the treatment of AGEN2034(anti PD-1) administered with placebo(Treatment Arm 1 -monotherapy), or with AGEN1884 (anti-CTLA4) (Treatment Arm 2 - combination therapy), defined as the binomial proportion of intent to treat(ITT) patients with best overall response(BOR) of complete response (CR) or partial response (PR), in women with recurrent/persistent/metastatic cervical cancer who have progressed following first-line therapy. BOR will be determined by the Independent Radiology Review Committee (IRRC), according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

Treatments

Therapies

Medications

AGEN1884 (); AGEN2034 (); Placebo ()

Inclusion Criteria

Inclusion Criteria

  • 18 years of age or older, and voluntarily agree to participate by giving written informed consent. (Participation in pharmacogenomics testing is optional)
  • Have (1) a histologically or cytologically confirmed diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and (2) metastatic, locally advanced, and/or unresectable disease at the time of enrollment. Histologic confirmation of the original primary tumor is required via pathology report. Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma, and mesonephric carcinoma. Has cervical cancer and has relapsed after a platinum-based treatment (first line) regimen for advanced (recurrent, unresectable, or metastatic) disease. Note: Patient receiving chemotherapy concurrently with primary radiation (e.g., weekly cisplatin) or patient receiving adjuvant chemotherapy following completion of radiation therapy (e.g., paclitaxel and carboplatin for ≤ 4 cycles) and progressed within 6 months after treatment completion will be eligible as this systemic therapy will be considered as first-line treatment.
  • Measurable Disease on imaging based on RECIST version 1.1 by investigator assessment.
  • Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Have adequate organ function as indicated by laboratory values per protocol.
  • Have no history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous-cell carcinoma of the skin, and has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
  • Patients must provide a sufficient and adequate formalin-fixed paraffin embedded (FFPE) tumor tissue sample preferably from the most recent biopsy of a tumor lesion, collected either at the time of or after the diagnosis of advanced or metastatic disease has been made AND from a site not previously irradiated. If no tumor tissue is available, a fresh biopsy will be required. Note: Tissue from needle or excisional biopsy or from resection is required.
  • Patients must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication) if of childbearing potential or be of non-child bearing potential. Non-childbearing potential is defined per protocol.
  • If of childbearing potential, female patients must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 120 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
  • Is willing and able to comply with the requirements of the protocol.

  • Exclusion Criteria

    Exclusion Criteria

  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
  • Has an inadequate washout period prior to first dose of study drug defined as: (a) Received systemic cytotoxic chemotherapy or biological therapy within 3 weeks before first dose, (b) Received radiation therapy within 3 weeks before first dose, or (c) Had major surgery within 4 weeks before first dose.
  • Has received prior therapy with: (a) Any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies (b) More than 1 systemic treatment regimen for the advanced (recurrent, unresectable, or metastatic) cervical cancer for which the patient is considered for the study.
  • Has persisting toxicity related to prior therapy of National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE) Grade >1 severity. Note: Sensory neuropathy or alopecia of Grade ≤2 is acceptable.
  • Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
  • Has known severe hypersensitivity reactions to fully human monoclonal antibodies (NCI-CTCAE Grade ≥3), any history of anaphylaxis, or uncontrolled asthma.(i.e., ≥3 features of partly controlled asthma).
  • Has received systemic corticosteroid therapy ≤ 7 days prior to the first dose of trial treatment or receiving any other form of systemic immunosuppressive medication (corticosteroid use on study for management of immune-related adverse events (AE), and/or a premedication for IV contrast allergies/reactions is allowed). Patients who are receiving daily corticosteroid replacement therapy are an exception to this rule. Daily prednisone at doses of up to 5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy.
  • Has a central nervous system (CNS) tumor, metastasis(es), and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period OR identified prior to consent. Note: Patients with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at screening (based on 2 sets of brain images, performed ≥ 4 weeks apart, and obtained after the brain metastases treatment). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be minimal and be expected as sequelae from treated lesions. For individuals who received steroids as part of brain metastases treatment, steroids must be discontinued ≥ 7 days prior to first dose of study drug.
  • Has active or history of autoimmune disease that has required immunosuppressive systemic treatment within 2 years of the start of trial treatment (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 immunosuppressive systemic treatment. Note: Patients with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
  • Has had an allogeneic tissue/solid organ transplant.
  • Has or had interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or IV corticosteroids.
  • Has an active infection requiring intravenous (IV) systemic therapy.
  • Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Other exclusions apply

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