Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

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

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Farletuzumab

Tubulin Modulators

Antimitotic Agents

Farletuzumab (FAR) at 2.5 mg/kg was administered by intravenous (IV) infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles.

MORAb-003 (farletuzumab)

Placebo (0.9% normal saline) was administered by IV infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles.

0.9% Saline

The study is being conducted to find out if paclitaxel works better when given together with an experimental drug called MORAb-003 (farletuzumab) or alone in patients with platinum-resistant or refractory relapsed ovarian cancer

Safety was assessed by the monitoring and recording of all adverse events (AEs), including drug hypersensitivity adverse events (DHAE), and serious adverse events (SAEs); clinical laboratory test (serum chemistry, hematology, urinalysis); tolerability (discontinuations, treatment delays, dose reductions); physical examinations (including vital signs assessment); 12-lead electrocardiograms (ECG) obtained in triplicate and reviewed by independent blinded cardiologist, and Karnofsky's performance status.

An Efficacy and Safety Study of MORAb-003 in Platinum-Resistant or Refractory Relapsed Ovarian Cancer

A Randomized, Double Blind, Placebo-Controlled Study of the Efficacy and Safety oF MORAb-003(Farletuzumab) in Combination With Paclitaxel Therapy in Subjects With Platinum-Resistant or Refractory Relapsed Ovarian Cancer

Due to termination of the study, data were not collected and the outcome measure for PFS based on GCIG was not analyzed.

Due to termination of the study, data were not collected and the outcome measure for Serologic Response Rate was not analyzed.

PFS was defined as the time (in months) from the date of randomization to the date of the first observation of progression as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST), or death regardless of cause. If progression or death was not observed, the PFS time was censored at the date of the last tumor assessment without evidence of progression before the date of initiation of further antitumor treatment, or the cutoff date (whichever was earlier).

OS was defined as the time (in months) from the date of randomization to the date of death, whatever the cause. If death was not observed for a participant, the survival time was censored on the last date the participant was known to be alive or the cutoff date, whichever was earlier.

BOR was defined as the percentage of participants having either a confirmed complete response (CR) or confirmed partial response (PR) using modified RECIST criteria by independent radiologist review. RECIST criteria was adjusted based on current medical practices and on possible differences between ovarian cancer and other solid tumors. Tumor assessments performed up to the initiation of further antitumor treatment were considered. Target lesions selected for response assessment were measured using computed tomography (CT) or magnetic resonance imaging (MRI) scans then graded according to the modified RECIST criteria, adjusted based on current medical practices and on possible differences between ovarian cancer and other solid tumors. Participants were assigned to one of the categories of change in disease state; CR, PR, progressive disease (PD), stable disease ( S)D, or not evaluable (NE).

TTR was derived for those participants with objective evidence of CR or PR, and was defined as the time (in months) from the date of randomization to the first documentation of object tumor response (TR). Analysis was based on the Kaplan-Meier estimated percentage of responders. This statistical analysis method measures the effect of study drug on tumor response over a period of time.

Morphotek

Safety Analysis Set was defined as all randomized participants who received any dose of FAR or placebo, analyzed according to the test article received. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 was used to grade severity of AEs. Treatment-emergent adverse events were reported.

Farletuzumab (FAR) at 2.5 mg/kg was administered by intravenous (IV) infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles. Paclitaxel (80 mg/m\^2) was administered weekly by IV infusion over 1 hour following administration of FAR. During the 4-week cycle, Week 4 was to be a rest period with no study treatment (test article or paclitaxel) administered. All participants were required to be premedicated with steroids before paclitaxel administration, and with acetaminophen (650 mg orally) or clinically equivalent per clinic routine within 4 hours prior to test article infusion.

MORAb-003 (Farletuzumab) Plus Paclitaxel

An equivalent volume of placebo (0.9% normal saline) was administered by IV infusion weekly on Day 1 of Weeks 1 to 12 (Cycle 1) and then in 4-week cycles with treatment administered on Day 1 of Weeks 1 to 3 for all subsequent cycles. Paclitaxel (80 mg/m\^2) was administered weekly by IV infusion over 1 hour following administration of FAR. During the 4-week cycle, Week 4 was to be a rest period with no study treatment (test article or paclitaxel) administered. All participants were required to be premedicated with steroids before paclitaxel administration, and with acetaminophen (650 mg orally) or clinically equivalent per clinic routine within 4 hours prior to test article infusion.

Placebo (Normal Saline) Plus Paclitaxel

Total

Age, Continuous

Sex: Female, Male

Intent-to-Treat population included, the primary population for the evaluation of efficacy, was defined as all participant who were randomly assigned to test article, analyzed by the treatment assigned.

This study was prematurely terminated by the sponsor following results of the preplanned futility analysis showing the study was unlikely to meet its statistically-defined coprimary endpoints.

Eisai Medical Services

Intent-To-Treat (ITT) population included all participants who were randomly assigned to study drug, analyzed by treatment assignment.

Progression-Free Survival (PFS)

ITT population included all participants who were randomly assigned to study drug and analyzed by the treatment assigned.

Overall Survival (OS)

Complete response (CR)

Partial response (PR)

Best Overall Response

ITT population (Responders only) included all participants who were randomly assigned to study drug and analyzed by the treatment assigned.

Time to Tumor Response (TTR)

Progression Free Survival Based on Gynecologic Cancer InterGroup (GCIG)

Serologic Response Rate

Overall Study

Amino Acids

Bevacizumab

Erlotinib Hydrochloride

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

bevacizumab

erlotinib

David S Alberts, MD

The purpose of this project is to determine if a new combination of drugs, erlotinib (Tarceva™) and bevacizumab is safe and effective for treating women diagnosed with ovarian cancer whose cancer has progressed while on prior standard chemotherapy treatment with a taxane (paclitaxel or docetaxel) and a platinum (cisplatin or carboplatin).

Erlotinib and bevacizumab, novel biologics, offer a new regimen for the treatment of ovarian cancer in women who are refractory to standard drug regimens. Because bevacizumab is an anti-angiogenesis drug and erlotinib is an EGFR receptor inhibitor their combination would lead to the inhibition of multiple signal transduction pathways and the reversal of cancer progression in this difficult to treat population. The study seeks to determine the efficacy and safety of the EGFR receptor inhibitor, erlotinib plus the anti-angiogenesis VEGF ligand inhibitor bevacizumab in women with platinum and taxane refractory ovarian cancer.

The study design is a non-randomized, open label, single center Phase II trial using a Simon two stage design. Eligible patients are women who have a histologically or pathologically confirmed diagnosis of epithelial carcinoma of the ovary or primary peritoneal carcinoma who have relapsed or are refractory to therapy after primary treatment of their disease.

Patients will be treated with erlotinib 150 mg/day orally and bevacizumab 10mg/kg every two weeks plus or minus one day intravenously. Forty patients will be enrolled in the study. Initially 20 eligible patients will be accrued. If one or no confirmed response is observed, the trial will be closed and the agents considered inactive. Otherwise, 20 additional eligible patients will be accrued for a total of 40 patients. Eight or more responses out of 40 will be considered evidence warranting further study of the agents provided other factors, such as progression-free and overall survival, also appear favorable.

Previous studies of this combination in non-small cell lung cancer, renal cell carcinoma and metastatic breast cancer have indicated a potential synergistic effect for these two agents. Preliminary data for the use of bevacizumab in advanced ovarian cancer indicates that this agent has single-agent activity. As a result, the researchers are interested in exploring the role of the combination of erlotinib and bevacizumab in advanced ovarian cancer.

Bevacizumab and Erlotinib Study in Advanced Ovarian Cancer

Phase II Open-Label Trial of Erlotinib (Tarceva) and Bevacizumab in Women With Advanced Ovarian Cancer

Objective response was defined using standard RECIST criteria. CR(complete response)= disappearance of all target lesions PR(partial response)=30% decrease in the sum of the longest diameter of target lesions PD(progressive disease)=20% increase in the sum of the longest diameter of target lesions SD(stable disease)= small changes that do not meet above criteria

Response duration=time (in weeks) between date of measurable response and date of progression (progression=20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed or baseline, progression of non-measurable disease in opinion of treating physician, any new lesion/site, death due to disease)if known or the date the subject went off protocol if they were still considered responders (ie do not qualify as progression) or are stable (Does not qualify for CR, PR, progression or Symptomatic Deterioration)

PFS was defined as the time from the start of therapy to the time of the first documentation of progression(progression=20% increase in sum of longest diameters of target measurable lesions over smallest sum observed or baseline, progression of non-measurable disease in the opinion of treating physician, appearance of new lesion/site, Death due to disease), symptomatic deterioration (global deterioration of health status requiring discontinuation of treatment without objective evidence of progression), or death due to any cause;

Genentech, Inc.

University of Arizona

This is an open label study. All subjects received erlotinib 150 mg/day orally and bevacizumab 10 mg/kg intravenously every 2 weeks until disease progression. Progression free survival (PFS) was defined as the time from the start of therapy to the time of the first documentation of progression, symptomatic deterioration, or death due to any cause

Bevacizumab and Erlotinib

Age, Categorical

Age Continuous

United States

Region of Enrollment

Setsuko K. Chambers, M.D.

Complete Response

Partial Response

Stable Disease

Disease Progression

Population=subjects receiving 1 dose of intervention and one assessment post-baseline. One subject=not evaluable. Analysis-Enroll 40, initial accrual of 20. If ≤1 confirmed responses observed in 20=closure. If ≥2 responses=20 additional.

Objective Response (Complete Partial, Stable and Progression)

The population analyzed included all participants receiving at least 1 dose of study intervention and at least one assessment post-baseline. One subject was not evaluable. Analysis was per protocol

Progression Free Survival(PFS)

Responders

Stable

Median Response Duration (Weeks)

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Digestive System Diseases

Breast Neoplasms

Recurrence

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Breast Diseases

Skin Diseases

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Fallopian Tube Cancer

Antirheumatic Agents

Anti-Infective Agents

Dermatologic Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Analgesics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Cyclosporine

Cyclosporins

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Interleukin-2

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Clotrimazole

Miconazole

Antifungal Agents

Calcineurin Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

Antineoplastic Agents, Hormonal

Analgesics, Non-Narcotic

Patients receiving Cyclosporine (CsA) and Natural Killer (NK) cells infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 6 doses given post NK cell infusion.

Patients receiving Cyclosporine (CsA), methylprednisolone and natural killer cells (NK) infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 6 doses given post NK cell infusion.

Patients receiving Cyclosporine (CsA), methylprednisolone and natural killer (NK) cells infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 6 doses given post NK cell infusion.

Patients receiving Cyclosporine (CsA), no methylprednisolone, eliminating IL-2 doses 4-6 and receiving Natural Killer (NK) cells infusion (created from donor lymphapheresis) after preparative regimen of Fludarabine and Cyclophosphamide. Interleukin-2 (IL-2) 6 million units 3 times a week x 3 doses given post NK cell infusion.

Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).

Administered intravenously, 60 mg/kg, days -5 and -4.

Administered intravenously, CsA 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14

Administered by infusion over less than 1 hour, no more than 8.0 x 10\^7 cells/kg will be given.

Natural killer cells

Will be given subcutaneously at 9 million units 3 times a week for a total of 6 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, will be given at 5 million units/m\^2 3 times per week for 6 doses).

IL-2

Administered intravenously (IV) 10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9

Administered intravenously (IV) 1 mg/kg Days -2 to +9

Will be given subcutaneously at million units 3 times a week for a total of 3 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, will be given at 3 million units/m\^2 3 times per week for 6 doses).

Melissa Geller, MD

This is a single center phase II trial designed to optimize a clinical platform of lymphodepleting chemotherapy and T-cell suppression to promote the persistence, function, and expansion of allogeneic natural killer (NK) cells in patients with recurrent ovarian, fallopian tube, primary peritoneal cancer and advanced metastatic breast cancer.

The donor NK cells are infused on day 0, after a non-myeloablative preparative regimen of cyclophosphamide and fludarabine plus a cyclosporine A (CsA) based immunosuppressive therapy. Subcutaneous interleukin-2 (IL-2) is started the evening of the NK infusion and continued three times a week for 6 doses total.

Up to 4 sequential immunosuppressive platforms will be tested (Arms 1 and 2 are currently closed) to identify a platform where patients have the potential for successful NK cell expansion (defined as an absolute circulating donor derived NK cell count of \> 100 cells/μl 14 days after NK cell infusion). Once a clinical platform is determined, the platform will be expanded to a total of 18 patients. The primary goal of this extended phase is to obtain preliminary efficacy information.

Follow-up for disease response is for 1 year from the NK cell infusion, with the possibility of re-treatment for patients who experience at least a clinical benefit who progress after 6 months.

Allogeneic Natural Killer (NK) Cells for Ovarian, Fallopian Tube, Peritoneal and Metastatic Breast Cancer

Lymphodepleting Chemotherapy and T-Cell Suppression Followed By Allogeneic Natural Killer Cells and IL-2 in Patients With Recurrent Ovarian, Fallopian Tube, Primary Peritoneal Cancer and Advanced Metastatic Breast Cancer (MT2009-30)

Response includes Complete Response (CR), Partial Response (PR), and Stable Disease (SD) as defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v.1.1) for target lesions and assessed by CT or MRI. Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease.

Time from study entry until progressive disease or data collection cutoff.

Masonic Cancer Center, University of Minnesota

Fludarabine: Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).

Cyclophosphamide: Administered intravenously, 60 mg/kg, days -5 and -4.

Cyclosporine (CsA): Administered intravenously, 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14

Natural Killer cells: Administered by infusion over less than 1 hour; no more than 8.0 x 10\^7 cells/kg will be given.

Interleukin- 2 (IL-2): Given subcutaneously at 9 million units 3 times a week for a total of 6 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, IL-2 will be given at 5 million units/m\^2 3 times per week for 6 doses).

Arm 1: CsA

Fludarabine: Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).

Cyclophosphamide: Administered intravenously, 60 mg/kg, days -5 and -4.

Cyclosporine (CsA): Administered intravenously, 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14

Natural Killer cells: Administered by infusion over less than 1 hour; no more than 8.0 x 10\^7 cells/kg will be given.

Interleukin- 2 (IL-2): Given subcutaneously at 9 million units 3 times a week for a total of 6 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, IL-2 will be given at 5 million units/m\^2 3 times per week for 6 doses).

Methylprednisolone: Administered intravenously,10 mg/kg Days -2 to +4 and 1 mg/kg Days +5 to +9.

Arm 2: CsA/Methylprednisolone (10mg)/6 Doses of Interleukin-2

Fludarabine: Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).

Cyclophosphamide: Administered intravenously, 60 mg/kg, days -5 and -4.

Cyclosporine (CsA ): Administered intravenously, 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14

Natural Killer cells: Administered by infusion over less than 1 hour; no more than 8.0 x 10\^7 cells/kg will be given.

Interleukin- 2 (IL-2): Given subcutaneously at 9 million units 3 times a week for a total of 6 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, IL-2 will be given at 5 million units/m\^2 3 times per week for 6 doses).

Methylprednisolone: Administered intravenously, 1 mg/kg Days -2 to +9

Arm 3: CsA/Methylprednisolone (1mg)/6 Doses of Interleukin-2

Dr. Melissa Geller

Response Rate

Number of participants with progressive disease at one year:

Arm 1: 2 out of 3; Arm 2: 1 out of 3; Arm 3: 5 out of 7

Time to Disease Progression

Number of Participants With Progressive Disease at One Year

Overall Survival

Fludarabine: Administered intravenously, 25 mg/m\^2, days -6 through -2 (5 days).

Cyclophosphamide: Administered intravenously, 60 mg/kg, days -5 and -4.

Cyclosporine (CsA ): Administered intravenously, 1.5 mg/kg for target dose range of 150-250 ng/mL day -3 through day +14

Natural Killer cells: Administered by infusion over less than 1 hour; no more than 8.0 x 10\^7 cells/kg will be given.

Interleukin-2 (IL-2): Given subcutaneously at 9 million units 3 times a week for a total of 3 doses, beginning 4 hours after NK cell infusion. (For patients weighing less than 45 kilograms, IL-2 will be given at 3 million units/m\^2 3 times per week for 3 doses).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Efficacy and Safety Study of MORAb-003 in Platinum-Resistant or Refractory Relapsed Ovarian Cancer	NCT00738699	Ovarian Cancer	MORAb-003 (farl... 0.9% Saline Paclitaxel	18 Years - 99 Years	Morphotek
Bevacizumab and Erlotinib Study in Advanced Ovarian Cancer	NCT00130520	Ovarian Neoplas...	bevacizumab erlotinib	18 Years -	University of Arizona
Allogeneic Natural Killer (NK) Cells for Ovarian, Fallopian Tube, Peritoneal and Metastatic Breast Cancer	NCT01105650	Ovarian Cancer Fallopian Tube ... Primary Periton... Breast Cancer	Fludarabine Cyclophosphamid... Cyclosporine Natural killer ... IL-2 Methylprednisol... Methylprednisol... Interleukin-2	18 Years -	Masonic Cancer Center, University of Minnesota
Allogeneic Natural Killer (NK) Cells for Ovarian, Fallopian Tube, Peritoneal and Metastatic Breast Cancer	NCT01105650	Ovarian Cancer Fallopian Tube ... Primary Periton... Breast Cancer	Fludarabine Cyclophosphamid... Cyclosporine Natural killer ... IL-2 Methylprednisol... Methylprednisol... Interleukin-2	18 Years -	Masonic Cancer Center, University of Minnesota
An Efficacy and Safety Study of MORAb-003 in Platinum-Resistant or Refractory Relapsed Ovarian Cancer	NCT00738699	Ovarian Cancer	MORAb-003 (farl... 0.9% Saline Paclitaxel	18 Years - 99 Years	Morphotek

Spots Global Cancer Trial Database for refractory ovarian cancer