Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Rare Diseases

Recurrence

Carcinoma

Adenocarcinoma

Carcinoma, Transitional Cell

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cystadenocarcinoma, Serous

Adenocarcinoma, Clear Cell

Cystadenocarcinoma

Cystadenocarcinoma, Mucinous

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Carcinoma, Endometrioid

Neoplasms, Cystic, Mucinous, and Serous

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Endometrial Neoplasms

Uterine Neoplasms

Ovarian Cancer

Transitional Cell Carcinoma

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Adenocarcinoma of the Appendix

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Vaccines

Folic Acid

Vitamin B Complex

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

INDUCTION PHASE: Patients receive folate receptor alpha peptide-loaded dendritic cell vaccine ID on day 1. Treatment repeats every 3 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients receive folate receptor alpha peptide-loaded dendritic cell vaccine ID on day 1. Treatment repeats every 3 months for 7 courses in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Multi-epitope Folate Receptor Alpha-loaded Dendritic Cell Vaccine

Matthew S. Block, M.D., Ph.D.

This pilot clinical trial studies the safety and immunogenicity of vaccine therapy in treating patients with stage IIIC-IV ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer following surgery and chemotherapy. Vaccines made from a person's peptide treated white blood cells may help the body build an effective immune response to kill tumor cells.

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of folate receptor alpha dendritic cell (FRalphaDC) vaccination (folate receptor alpha-peptide loaded dendritic cell vaccine).

SECONDARY OBJECTIVES:

I. Measure time to disease recurrence of patients treated with FRalphaDCs. II. Measure overall survival of patients treated with FRalphaDCs.

TERTIARY OBJECTIVES:

I. Determine whether FRalphaDC vaccination induces an increase in the number of FRalpha-specific interleukin (IL)-17-secreting T helper (Th) cells, as determined by enzyme-linked immunosorbent spot (ELISpot).

II. Determine whether FRalphaDC vaccination induces an increase in the number of FRalpha-specific T cells that secrete interferon (IFN)gamma, tumor necrosis factor (TNF)alpha, IL-10, and granzyme B, as determined by ELISpot.

III. Determine whether FRalphaDC vaccination induces antibodies specific for FRalpha.

IV. Determine whether FRalphaDC vaccination induces a delayed type hypersensitivity (DTH) skin reaction specific for FRalpha.

V. Measure FRalpha expression in patients' primary tumors and in tumors that recur after FRalphaDC vaccine treatment (when available).

VI. Determine whether FRalphaDC vaccination is associated with changes in peripheral blood immune cell subsets.

OUTLINE: This is a dose-escalation study.

INDUCTION PHASE: Patients receive folate receptor alpha peptide-loaded dendritic cell vaccine intradermally (ID) on day 1. Treatment repeats every 3 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients receive folate receptor alpha peptide-loaded dendritic cell vaccine ID on day 1. Treatment repeats every 3 months for 7 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.

Vaccine Therapy for Patients With Stage IIIC-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

A Pilot Study of the Safety and Immunogenicity of Folate Receptor Alpha Peptide-Loaded Dendritic Cell Vaccination in Patients With Advanced Stage Epithelial Ovarian Cancer

Assessed using simple summary statistics (mean and 95% confidence interval.

The percent of each category will be calculated along with a 95% confidence interval.

If the accrual schema is completed and there are fewer than 5 patients with a DLT, the vaccination treatment will be considered safe in this patient population.

The Kaplan-Meier method will be used to estimate the distribution of OS.

The Kaplan-Meier method will be used to estimate the distribution of TDR.

Mayo Clinic

Patients undergo MIS within 6 weeks after last cycle of standard of care neoadjuvant chemotherapy. If during MIS the surgeon thinks complete gross resection can only be accomplished by performing an open procedure, patients may undergo laparotomy instead. Within 6 weeks after surgery, patients receive standard of care chemotherapy.

Patients undergo laparotomy within 6 weeks after last cycle of standard of care neoadjuvant chemotherapy. Within 6 weeks after surgery, patients receive standard of care chemotherapy.

Chemotherapy

Laparotomy

Minimally Invasive Surgery

Quality-of-Life Assessment

Questionnaire Administration

Jose A. Rauh-Hain

Abdulrahman Sinno, MD

Alexander Melamed, MD

Leah McNally, MD

Jose Rauh-Hain, MD

Lisa Barroilhet, MD

Jose A Rauh-Hain

This phase III trial compares minimally invasive surgery (MIS) to laparotomy in treating patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who are receiving chemotherapy before and after surgery (neoadjuvant chemotherapy). MIS is a surgical procedure that uses small incision(s) and is intended to produce minimal blood loss and pain for the patient. Laparotomy is a surgical procedure which allows the doctors to remove some or all of the tumor and check if the disease has spread to other organs in the body. MIS may work the same or better than standard laparotomy after chemotherapy in prolonging the return of the disease and/or improving quality of life after surgery.

PRIMARY OBJECTIVE:

I. To examine whether MIS is non-inferior to laparotomy in terms of disease free survival (DFS) in women with advanced stage epithelial ovarian cancer (EOC) that received 3 to 4 cycles of neoadjuvant chemotherapy (NACT).

SECONDARY OBJECTIVES:

I. To determine if there are differences in health-related quality of life (HR-QoL) in patients undergoing MIS versus (vs) laparotomy as assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30), QLQ-Ovarian Cancer Module (OV28), and Functional Assessment of Cancer Therapy-General (FACT-G7).

II. To determine if there are differences between patients undergoing MIS vs laparotomy in the rate of optimal cytoreduction (defined as residual tumor nodules each measuring 1 cm or less in maximum diameter) and complete cytoreduction (defined as no evidence of macroscopic disease).

III. To examine whether MIS is non-inferior to laparotomy in terms of overall survival (OS) in women with advanced stage EOC that received 3 to 4 cycles of NACT.

IV. To determine if there are differences between patients undergoing MIS vs laparotomy in surgical morbidity and mortality, intraoperative injuries, and post-operative complications.

V. To determine the rates of MIS converted to laparotomy and the reasons.

VI. To determine if there are any difference in costs and cost-effectiveness between patients undergoing MIS vs laparotomy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo MIS within 6 weeks after last cycle of standard of care neoadjuvant chemotherapy. If during MIS the surgeon thinks complete gross resection can only be accomplished by performing an open procedure, patients may undergo laparotomy instead. Within 6 weeks after surgery, patients receive standard of care chemotherapy.

ARM B: Patients undergo laparotomy within 6 weeks after last cycle of standard of care neoadjuvant chemotherapy. Within 6 weeks after surgery, patients receive standard of care chemotherapy.

After completion of study, patients are followed up within 6 weeks of completing post-surgery chemotherapy, then every 3 months for the first 2 years, and then every 6 months for 3 years.

Minimally Invasive Surgery After Neoadjuvant Chemotherapy for the Treatment of Stage IIIC-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer, LANCE Trial

Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy

Kaplan Meier curves will be used to describe DFS over time. Log-rank test will be used to compare DFS between the control and experimental arms. The treatment effects will be summarized by means of a hazard ratio with its associated 95% confidence interval. Two years DFS rate will be computed with a targeted 95% confidence interval (CI).

HR-QoL of patients will be assessed with European Organization for Research and Treatment of Cancer (EORTC Scale 1-Not at all, 2-A little bit, 3-Quite a bit, 4-Very Much)

HR-QoL of patients will be assessed Quality of Life Questionnaire-Core 30 (QLQC30 scale 1-Not at all, 2-A little bit, 3-Quite a bit, 4-Very Much)

HR-QoL of patients will be assessed with QLQ-Ovarian Cancer Module (OV28 Scale 1- Not at all, 2- A little bit, 3-Quite a bit, 4-Very Much).) (ovarian supplement)

HR-QoL of patients will be assessed with Functional Assessment of Cancer Therapy-General short-form (FACT-G7 Scale 1- Not at all, 2- A little bit, 3-Quite a bit, 4-Very Much).

Defined as residual tumor nodules each measuring 1 cm or less in maximum diameter.

Defined as no evidence of macroscopic disease.

Overall survival will be estimated using the Kaplan-Meier method, and will be described using the median with its 95% CI. Univariate Cox proportional hazards model (i.e., logrank test) will be used to estimate hazard ratios (HR: control arm versus investigational arm) with a 95% CI. When appropriate, multivariate Cox analyses will be performed, in which a univariate selection procedure will serve to identify eligible explanatory variables with univariate Cox (using Wald test) p-value lower than 0.10 as potential prognostic value. Follow-up will be estimated using the reverse Kaplan-Meier method, and will be described using the median with its 95% CI.

Rates of surgical complications according to Surgical morbidity (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0 \& Clavien Dindo classification and mortality (30-day post-operative for adverse events and up to 6 months post-operative for adverse events of interest).

Mortality rates (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0 \& Clavien Dindo classification and mortality (30-day post-operative for adverse events and up to 6 months post-operative for adverse events of interest).

Coded as yes or no and categorized as involving the bowel, veins, arteries, ureter, bladder, or other site.

Prospectively completed forms documented reasons for conversion of MIS to laparotomy.

A cost analysis may be performed in some countries.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Immune System Diseases

Hypersensitivity

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Olaparib

Immunoglobulins

Tremelimumab

Poly(ADP-ribose) Polymerase Inhibitors

Ipilimumab

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive olaparib PO BID in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection throughout the trial.

Patients receive olaparib as in Arm I. Patients also receive tremelimumab IV over 60 minutes on day 1. Cycles of tremelimumab repeat every 4 weeks for 4 doses and then every 12 weeks for up to 2 years total in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection throughout the trial.

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Sarah F Adams

This phase II trial studies how well olaparib with or without tremelimumab works in treating patients with ovarian, fallopian tube, or peritoneal cancer that has come back (recurrent). PARPs are proteins that help repair deoxyribonucleic acid (DNA) mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Immunotherapy with monoclonal antibodies, such as tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving olaparib and tremelimumab together may work better than olaparib alone in treating patients with ovarian, fallopian tube, or peritoneal cancer.

PRIMARY OBJECTIVES:

I. To determine whether olaparib plus tremelimumab has adequate safety in the study population. (Safety Lead-in Trial Components) II. To compare the progression-free survival (PFS) duration of olaparib monotherapy versus olaparib plus tremelimumab in women with recurrent, platinum sensitive ovarian, primary peritoneal, or fallopian tube cancer. (Phase II Trial Component)

SECONDARY OBJECTIVES:

I. To compare the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in women with recurrent, platinum sensitive ovarian, primary peritoneal or fallopian tube cancer treated with either olaparib monotherapy or olaparib plus tremelimumab.

II. To compare the overall survival (OS) of women with recurrent, platinum sensitive ovarian, primary peritoneal or fallopian tube cancer treated with either olaparib monotherapy or olaparib plus tremelimumab.

EXPLORATORY OBJECTIVES:

I. To explore whether conditions in the tumor microenvironment (as measured by gene expression signature in archived tumor samples) identify patients that benefit from combined olaparib and tremelimumab immunotherapy.

II. To explore whether mutations in BRCA1/2 genes or other evidence of homologous repair deficiency (HRD+) is prognostic and/or predictive of response to combined olaparib and tremelimumab immunotherapy.

III. To explore associations between PD1 expression in the tumor microenvironment and outcome and changes in circulating leukocyte populations.

IV. To explore the correlation between tumor mutational burden and response to olaparib and tremelimumab immunotherapy.

V. To explore the impact of olaparib and tremelimumab versus olaparib monotherapy on circulating leukocyte subsets via exploration of the immunomodulatory effects of PARP inhibition and the added impact of CTLA4 blockade in this patient population.

VI. To explore cytokine/chemokine levels using a multiplex immunoassay (Olink) and correlate these levels with clinical endpoints.

VII. To use cell-free deoxyribonucleic acid (DNA) to assess BRCA mutation status as a mechanism of acquired resistance to prior PARP inhibition and to compare with treatment efficacy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive olaparib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) as well as blood sample collection throughout the trial.

ARM II: Patients receive olaparib as in Arm I. Patients also receive tremelimumab intravenously (IV) over 60 minutes on day 1. Cycles of tremelimumab repeat every 4 weeks for 4 doses and then every 12 weeks for up to 2 years total in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI as well as blood sample collection throughout the trial.

After completion of study treatment, patients are followed up monthly for 3 months, then every 3 months for 2 years, followed by every 6 months for 3 years.

Testing the Addition of an Immunotherapy Drug, Tremelimumab, to the PARP Inhibition Drug, Olaparib, for Recurrent Ovarian, Fallopian Tube or Peritoneal Cancer

A Phase II Randomized Trial of Olaparib Versus Olaparib Plus Tremelimumab in Platinum-Sensitive Recurrent Ovarian Cancer

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

The count of participants who have progressed or died (death due to any cause). Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Summary of RECIST 1.1 criteria for progression for this trial: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

The outcome measure presents the count of participants who experienced a DLT. If more than six of the first 25 patients treated with Tremelimumab and Olaparib are unable to complete at least 3 cycles of treatment due to DLTs then the study will be stopped. If not, then enrollment will continue until 45 patients are enrolled. If more than 11 of the first 45 patients treated with the combination regimen are unable to complete the first 3 cycles of treatment, then enrollment will be stopped, otherwise, the trial till proceed to the third component (i.e. a phase 2 comparison of study treatments).

The objective response (RECIST 1.1) is the count of subjects with a best overall complete response (CR) or partial response (PR) among those with target lesions at the time of enrollment. : Summary of RECIST 1.1 criteria for progression for this trial: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Overall survival (OS) will be presented as survival events (deaths).

Safety data will be summarized for all treated subjects. All adverse events, including severe adverse events (SAEs) and treatment-related adverse events, will be categorized and graded for severity according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. This will be presented as the count of participants who experienced an adverse event (AE) of grade 3 or higher.

NRG Oncology

All adverse events, including severe adverse events (SAEs) and treatment-related adverse events, will be categorized and graded for severity according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. There is one less patient in the AE/SAE section than in the All Cause Mortality section. This is due to one patient never being treated. Therefore this patient is excluded from adverse events, however this patient was still followed for survival status.

Patients receive olaparib PO BID in the absence of disease progression or unacceptable toxicity.

Olaparib: Given PO

Arm I (Olaparib)

Patients receive olaparib as in Arm I. Patients also receive tremelimumab IV over 60 minutes on day 1. Cycles of tremelimumab repeat every 4 weeks for 4 doses and then every 12 weeks for up to 2 years total in the absence of disease progression or unacceptable toxicity.

Olaparib: Given PO

Tremelimumab: Given IV

Arm II (Olaparib, Tremelimumab)

Total

20 - 29 years

30 - 39 years

40 - 49 years

50 - 59 years

60 - 69 years

70 - 79 years

>= 80 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Christopher Purdy on behalf of Danielle Enserro, PhD

All randomized patients (intent to treat)

Progression Free Survival (PFS)

All patients who initiated treatment on Arm II and either 1) experienced a DLT or 2) completed three cycles. Patients randomized to Arm I are excluded from DLT assessment.

Dose-limiting Toxicity (DLT) (Safety Lead-In)

Odds ratio for experimental arm (O + T) response compared to control arm (O) response.

All randomized patients (intent to treat).

Objective Response (RECIST 1.1)

All randomized patients (intent-to-treat).

Number of Participants Died

All randomized patients who initiated treatment

Number of Participants With Adverse Event of Grade 3 or Higher

Patients receive olaparib (300 mg) PO BID in the absence of disease progression or unacceptable toxicity.

Olaparib: Given PO

Patients receive olaparib (300 mg) twice daily until disease progression or adverse events prohibit further treatment. Patients also receive tremelimumab (750 mg)\* IV over 60 minutes on day 1. Cycles of tremelimumab repeat every 4 weeks for 4 doses and then every 12 weeks for up to 2 years total in the absence of disease progression or unacceptable toxicity. \*If a patient's weight falls to less than or equal to 30 kg, the patient should receive weight-based dosing equivalent to 10 mg/kg of tremelimumab every 4 weeks.

Olaparib: Given PO Tremelimumab: Given IV

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vaccine Therapy for Patients With Stage IIIC-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer	NCT02111941	Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Ovarian Clear C... Ovarian Endomet... Ovarian Mucinou... Ovarian Seromuc... Ovarian Serous ... Ovarian Transit... Primary Periton... Recurrent Fallo... Recurrent Ovari... Recurrent Prima... Stage IIIC Fall... Stage IIIC Ovar... Stage IIIC Prim... Stage IV Fallop... Stage IV Ovaria... Stage IV Primar... Undifferentiate... Undifferentiate...	Laboratory Biom... Multi-epitope F...	18 Years -	Mayo Clinic
Minimally Invasive Surgery After Neoadjuvant Chemotherapy for the Treatment of Stage IIIC-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer, LANCE Trial	NCT04575935	Advanced Ovaria... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Ovarian Clear C... Ovarian Endomet... Ovarian Serous ... Ovarian Transit... Primary Periton... Primary Periton... Primary Periton... Primary Periton... Stage IIIC Fall... Stage IIIC Ovar... Stage IIIC Prim... Stage IV Fallop... Stage IV Ovaria... Stage IV Primar... Stage IVA Fallo... Stage IVA Ovari... Stage IVA Prima... Stage IVB Fallo... Stage IVB Ovari... Stage IVB Prima...	Chemotherapy Laparotomy Minimally Invas... Quality-of-Life... Questionnaire A...	18 Years -	M.D. Anderson Cancer Center
Testing the Addition of an Immunotherapy Drug, Tremelimumab, to the PARP Inhibition Drug, Olaparib, for Recurrent Ovarian, Fallopian Tube or Peritoneal Cancer	NCT04034927	Fallopian Tube ... Fallopian Tube ... Malignant Ovari... Ovarian High Gr... Platinum-Sensit... Platinum-Sensit... Platinum-Sensit... Primary Periton... Recurrent Fallo... Recurrent Fallo... Recurrent Ovari... Recurrent Ovari... Recurrent Prima... Recurrent Prima...	Biospecimen Col... Computed Tomogr... Magnetic Resona... Olaparib Tremelimumab	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for fallopian tube endometrioid tumor