A Randomized, Phase II/III Study of Pegylated Liposomal Doxorubicin and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin, CTEP-Supplied Bevacizumab and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin and CTEP-Supplied Bevacizumab in Platinum Resistant Ovarian Cancer

Plain English Summary

Pegylated Liposomal Doxorubicin Hydrochloride With Atezolizumab and/or Bevacizumab in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Fallopian Tube High Grade Serous Adenocarcinoma, Ovarian High Grade Serous Adenocarcinoma, Ovarian Seromucinous Carcinoma, Primary Peritoneal High Grade Serous Adenocarcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Fallopian Tube Clear Cell Adenocarcinoma, Recurrent Fallopian Tube Endometrioid Adenocarcinoma, Recurrent Fallopian Tube Undifferentiated Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Ovarian Clear Cell Adenocarcinoma. Tests pegylated liposomal doxorubicin with atezolizumab or bevacizumab for recurrent platinum-resistant ovarian cancer. For patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer who have not responded to previous treatments. Participation involves IV infusions of study drugs and regular check-ups. Alternatives include other chemotherapy and immunotherapy treatments. The trial aims to enroll 444 participants.

Official Summary

This phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent). Chemotherapy drugs, such as pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. It is not yet known which combination will work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if over 18, in good health, and has recurrent platinum-resistant ovarian cancer. Not eligible if had prior allogeneic bone marrow or solid organ transplantation. Must be able to provide informed consent and agree to use contraception if of child-bearing potential. Age: 18+; Health: Good overall health, no prior allogeneic bone marrow or solid organ transplants. This trial is studying Fallopian Tube High Grade Serous Adenocarcinoma, Ovarian High Grade Serous Adenocarcinoma, Ovarian Seromucinous Carcinoma, Primary Peritoneal High Grade Serous Adenocarcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Fallopian Tube Clear Cell Adenocarcinoma, Recurrent Fallopian Tube Endometrioid Adenocarcinoma, Recurrent Fallopian Tube Undifferentiated Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Ovarian Clear Cell Adenocarcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

Primary outcomes measure safety and effectiveness, providing crucial data for patient survival and quality of life. The specific primary outcome measures are: Incidence of Dose Limiting Toxicities (DLT) of Experimental Regimens (Up to 28 days); Progression Free Survival (PFS) (Phase II) (From study enrollment to the investigator determined date of progression or death due to any cause, whichever occurs first, assessed up to 5 years); PFS (Phase III) (From study enrollment to the investigator determined date of progression or death due to any cause, whichever occurs first, assessed up to 5 years.); Overall Survival (OS) (Phase III) (From study enrollment to the date of death regardless of the cause, assessed up to 5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical treatment gap for recurrent platinum-resistant ovarian cancer, offering potentially more effective options. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Fallopian Tube High Grade Serous Adenocarcinoma, Ovarian High Grade Serous Adenocarcinoma, Ovarian Seromucinous Carcinoma, Primary Peritoneal High Grade Serous Adenocarcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Fallopian Tube Clear Cell Adenocarcinoma, Recurrent Fallopian Tube Endometrioid Adenocarcinoma, Recurrent Fallopian Tube Undifferentiated Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Ovarian Clear Cell Adenocarcinoma, where improved treatment options are needed.

Investor Insight

Market size is significant, with a competitive landscape dominated by established players; approval probability is high given the unmet need. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor about your eligibility and the potential benefits and risks. Participation involves IV infusions of study drugs and regular check-ups. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 444 participants

Interventions

• DRUG: Atezolizumab — Given IV
• BIOLOGICAL: Bevacizumab — Given IV
• PROCEDURE: Computed Tomography — Undergo CT
• DRUG: Pegylated Liposomal Doxorubicin Hydrochloride — Given IV
• OTHER: Quality-of-Life Assessment — Ancillary studies

Primary Outcomes

• Incidence of Dose Limiting Toxicities (DLT) of Experimental Regimens (Up to 28 days)
• Progression Free Survival (PFS) (Phase II) (From study enrollment to the investigator determined date of progression or death due to any cause, whichever occurs first, assessed up to 5 years)
• PFS (Phase III) (From study enrollment to the investigator determined date of progression or death due to any cause, whichever occurs first, assessed up to 5 years.)
• Overall Survival (OS) (Phase III) (From study enrollment to the date of death regardless of the cause, assessed up to 5 years)

Secondary Outcomes

• Objective Response Rate (ORR) (Partial or Complete Response) (Phase II) (Up to 5 years)
• ORR (Partial or Complete Response) (Phase III) (Up to 5 years)
• Number of Patients With a Grade 3 (or Higher) Adverse Event (Phase II) (Up to 5 years)
• Number of Patients With a Grade 3 (or Higher) Adverse Event (Phase III) (Up to 5 years)
• Patient Reported Outcomes (Up to 2 years)

Full Eligibility Criteria

Inclusion Criteria:

* Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up
* Administration of study drugs (pegylated liposomal doxorubicin, bevacizumab, atezolizumab) may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. (06/29/2017)
* Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial
* High grade ovarian cancer, including high grade serous; clear cell; endometrioid, grade 3; and others (adenocarcinoma, not otherwise specified \[NOS\]; mixed epithelial carcinoma; undifferentiated carcinoma); NOTE: low grade serous, mucinous and carcinosarcoma histologies are excluded due to their different underlying genomic features and/or clinical behavior; ovarian cancer = ovarian, fallopian tube or primary peritoneal cancer; required data element: submission of pathology report
* Recurrent, platinum resistant ovarian cancer (defined as progression within \< 6 months from completion of platinum based therapy; the date should be calculated from the last administered dose of platinum therapy)
* 1-2 prior regimens (including primary therapy); hormonal therapies (e.g., tamoxifen, aromatase inhibitors) will not count toward the prior regimen limit; PARP inhibitors given in the maintenance setting post response to platinum-based therapy will not count as a separate regimen from the preceding platinum-based therapy. (30-OCT-2020)
* Measurable disease (defined by RECIST v1.1) or evaluable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease related in the setting of cancer antigen \[CA\] 125 \>= 2 x upper limit of normal \[ULN\])
* Age \>= 18
* Performance status 0, 1 or 2
* Absolute neutrophil count (ANC) \>= 1,500/mcl (within 14 days prior to registration)
* Platelets \>= 100,000/mcl (within 14 days prior to registration)
* Hemoglobin (Hgb) \>= 8 g/dl (within 14 days prior to registration)
* Creatinine =\< 1.5 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
* Urine protein creatinine (UPC) ratio must be \< 1.0 (within 14 days prior to registration); if UPC ratio \>= 1, collection of 24-hour urine measurement of urine protein is recommended (24-hour urine protein level must be \< 1000 mg for patient enrollment); If UPC ratio cannot be calculated because the urine protein is below the lower limit of detection of the assay this will not exclude the patient (10/22/2018) (30-OCT-2020); UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
* Total bilirubin =\< 1.5 x ULN (patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled) (within 14 days prior to registration)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x ULN (AST and/or ALT =\< 5 x ULN for patients with liver involvement) (within 14 days prior to registration)
* International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (or on stable dose of therapeutic anticoagulation, such as low-molecular-weight heparin, warfarin or rivaroxaban) (10/16/2017)
* Thyroid-stimulating hormone (TSH) within normal limits (Euthyroid patients on thyroid replacement therapy allowed provided TSH \< ULN) (02/20/2019)
* The patient or legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

* Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
* Patients who have had systemic anticancer therapy (e.g., chemotherapy, targeted therapy including PARP inhibitors or bevacizumab) within 3 weeks prior to entering the study (30-OCT-2020)
* Patients who have had hormonal therapy (e.g., tamoxifen, aromatase inhibitor) within 1 week prior to entering the study
* Patients with prior treatment with anti-programmed cell death (PD)-1, anti- programmed cell death ligand (PD-L)1 or anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 therapeutic antibody or other similar 

Trial Locations

• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• Fairbanks Memorial Hospital, Fairbanks, Alaska, United States
• CTCA at Western Regional Medical Center, Goodyear, Arizona, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Fallopian Tube High Grade Serous Adenocarcinoma
• Ovarian High Grade Serous Adenocarcinoma
• Ovarian Seromucinous Carcinoma
• Primary Peritoneal High Grade Serous Adenocarcinoma
• Recurrent Fallopian Tube Carcinoma
• Recurrent Fallopian Tube Clear Cell Adenocarcinoma
• Recurrent Fallopian Tube Endometrioid Adenocarcinoma
• Recurrent Fallopian Tube Undifferentiated Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Ovarian Clear Cell Adenocarcinoma

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