Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Digestive System Diseases

Rare Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Fallopian Tube Neoplasms

Peritoneal Neoplasms

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

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Carboplatin

Folic Acid

Vitamin B Complex

Vitamin B 12

Hydroxocobalamin

Trace Elements

Folinic Acid

Methylcobalamin

Folate

Vitamin B9

Vitamin B12

Cobalamin

Cyanocobalamin

Given intravenously on Day 1 of each 28-day cycle

carboplatin

Given intravenously on Day 1 and Day 15 of each 28-day cycle.

pralatrexate

Given orally on a daily basis starting 7 days before the first dose of pralatrexate and continuing until 30 days after the last dose of pralatrexate.

Given vitamin B12 injection no more than 10 weeks prior to the first dose of pralatrexate and every 8-10 weeks after the first dose of pralatrexate.

Vitamin B12 Injection

Marcela G. del Carmen, MD, MPH

Pralatrexate is a type of antifolate drug which means is restrains the production of folic acid in the body. Folic acids are used by tumors to increase tumor cell growth and division. It is believed that reducing folic acid will hinder the rapid division of tumor cells, their growth and production. Carboplatin is an FDA approved chemotherapy drug for ovarian, fallopian tube and primary peritoneal cancer. Some antifolate drugs are used with other chemotherapy drugs to enhance cancer-fighting characteristics. It is believed that the study drug pralatrexate may improve the anti-tumor effect of carboplatin. In this research study we are looking for the highest dose of pralatrexate that can be given safely in combination with carboplatin.

* Since we are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects, not everyone who participates will receive the same dose of the study drug.
* Each study cycle will last 28 days. On Day 1, participants will receive carboplatin intravenously. On Days 1 and 15 of each cycle they will receive pralatrexate intravenously. Participants will also be asked to take folic acid orally on a daily basis starting 7 days before the first dose of pralatrexate and continuing until 30 days after the last dose of pralatrexate. They will also receive a vitamin B12 injection no more than 10 weeks prior to the first dose of pralatrexate and every 8-10 weeks after the first dose of pralatrexate.
* Participants will come to the clinic on Day 1 and 15 of each cycle and have the following tests/procedures performed: Medical history; Vital signs; Blood tests, assessment of the tumor (every two cycles) and an EKG (before the start of cycle 2).
* In addition, during Cycle 1, participants will come to the clinic weekly for blood tests.
* Pharmacokinetic (PK) blood samples (to monitor how the body absorbs and breaks down the study drug) will be done at the following time points during Cycle 1: Day 1-3 and Day 15-17.
* Participants will be asked to take the study drugs for up to 6 cycles. They may continue beyond 6 cycles as long as there is evidence that the tumor is not growing and they are not experiencing any unacceptable side effects.

Carboplatin/Pralatrexate in Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer

Phase I/II Study of Carboplatin and Pralatrexate in Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer

The maximum tolerated dose of Pralatrexate in combination with Carboplatin in this patient population. The unit is given in milligrams per square meter of body surface area. MTD was determined using a standard 3 + 3 dose escalation cohort, where 3 participants were enrolled on the starting dose of 30 mg/m2 and if no dose limiting toxicities (DLT) were experienced after a full cycle, 3 additional participants were enrolled at the next highest dose level. Each increase in dose level escalated the dose of Pralatrexate by 15 mg/m2. If during any dose level, 1 patient out of 3 develops a DLT, then 3 additional patients will be added to that dose level. If 2 out of the 3 patients placed on any dose level experience a DLT, the preceding dose is considered MTD. If 1/6 has a DLT, the next higher dose level will commence accrual (unless at level +5 and then accrual to the Phase I portion will stop). If ≥ 2 of 6 patients have a DLT, then the preceding dose will be considered MTD.

Summary of the best overall responses to treatment as assessed by RECIST (Response Evaluation Criteria In Solid Tumors).

* Complete Response (CR): Disappearance of all target lesions
* Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
* Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
* Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

The number of participants still alive at the given time points. The duration of time is measured from the start of treatment until death due to any cause, participants are censored at the date of the last evaluation. The number participants surviving at 6, 12, 18, and 24 months is shown.

The number of participants alive and without disease progression at the given time-points. Time is measured from the start of treatment. Progression is defined as having at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Summary of the treatment related adverse events experienced by participants as assessed by Common Terminology Criteria for Adverse Events (CTCAE 4). Adverse events were assessed from the start of treatment until 30 days after the last dose of study drug.

The maximum concentration of Pralatrexate at day 1 and 15 among phase 1 participants dosed at 105 milligrams per square meter of body surface area (mg/m2). The concentration is given in micrograms per milliliter.

Area under the plasma drug concentration-time curve (AUC) for phase 1 participants that were dosed at 105 mg/m2. AUC represents the actual body exposure to drug after administration of a dose of the drug and is expressed in micrograms \* hour per milliliter (ug\*h/mL).

Dana-Farber Cancer Institute

Brigham and Women's Hospital

National Comprehensive Cancer Network

Massachusetts General Hospital

MD, MPH

carboplatin: Given intravenously on Day 1 of each 28-day cycle

pralatrexate: Given intravenously on Day 1 and Day 15 of each 28-day cycle.

Carboplatin/Pralatrexate

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black or African American

Other

Race/Ethnicity, Customized

United States

Region of Enrollment

Eastern Cooperative Oncology Group (ECOG) score

* 0: Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction)
* 1: Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work)

ECOG Performance Status

Primary Site

Histology Subtype

Marcela del Carmen, MD, MPH

The participants that participated in the phase 1 dose escalation portion of the study

Maximum Tolerated Dose (MTD)

Best Overall Response

6 Months

12 Months

18 Months

24 Months

Overall Survival

3 Months

Progression Free Survival

Constipation

Mucositis

Nausea

Vomiting

Diarrhea

Anemia

Thrombocytopenia

Neutropenia

Febrile neutropenia

Hypersensitivity reaction

Hypomagnesemia

Pruritis

Rash

Fatigue

Treatment Related Adverse Events

Day 1

Day 15

Participants that required a dose reduction due to an adverse event were excluded from the day 15 evaluation

Maximum Concentration of Drug in Plasma (Cmax)

Area Under the Plasma Drug Concentration-Time Curve (AUC)

Overall Study

Carcinoma

Carcinoma, Transitional Cell

Urinary Bladder Neoplasms

Disease Progression

Ureteral Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urologic Diseases

Male Urogenital Diseases

Ureteral Diseases

Transitional Cell Carcinoma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Pemetrexed

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Folic Acid Antagonists

Drug: Pemetrexed Maintenance therapy: 500 mg/m\^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation.

Drug: folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment

Drug: vitamin B12 injection 1000 μg IM 7 days prior to treatment initiation and the every then every 3 cycles until the end of treatment

Drug: dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment

observation group will be observed with best supportive care until progressive disease

Pemetrexed 500 mg/m2mixed in normal saline 100 mL as a 10 minute IV infusion on day 1 of each 21 day cycle

pemetrexed

folic acid 1000 μg daily orally from 7 days prior to treatment initiation until the end of treatment

vitamin B12 1000 μg IM 7 days prior to treatment initiation and the end of treatment

Dexamethasone 4 mg twice orally for 3 days beginning the day before treatment until the end of treatment to minimize cutaneous reactions

Jae-Lyun Lee, MD, PhD

MiRan Kim

Ho Young Kim

Jin Young Kim, MD

Jung Lim Lee

Hyo Jin Lee, MD, PhD.

Soo Jung Hong

Hyun Ae Jung

Inkeun Park, MD

Suee Lee

Il-Hwan Kim

Hyo Jung Kim

Hee Joon Kim, MD

Byeong Seok Sohn

Yun-Gyoo Lee

Yoon Ji Choi

Bhum Suk Keam

In-Ho Kim

Sang Joon Shin

Byoung Yong Shim

Yoon Ho Ko

Kwonoh Park

This study aims to verify superiority of pemetrexed maintenance to observation for patient without disease progression after 1 st line cisplatin-based chemotherapy.

Patients with unresectable locally advanced, recurrent, or metastatic urothelial carcinoma of bladder, ureter, or renal pelvis who do not experience disease progression after 4 to 6 cycles of 1 st line chemotherapy administration.

After completion of 4-6 cycles, patients without disease progression on CT which is taken within 3 weeks after administration of the last chemotherapy will be randomized within 4 weeks after administration of the last chemotherapy to assign either maintenance group or observation group.

Pemetrexed 500 mg/m 2 mixed in normal saline 100 mL as a 10 minute IV infusion on day 1 of each 21 day cycle, with vitamin supplementation (folic acid 1000μg daily orally from 7 days prior to treatment initiation and vitamin B12 1000 μg IM 7 days prior to treatment initiation and then every 3 cycles). Thereafter, vitamin B12 can be injected on the same day of pemetrexed infusion. Dexamethasone 4 mg orally twice daily for 3 days beginning the day before treatment to minimize cutaneous reactions.

Treatment continues until occurrence of disease progression or intolerable toxicities upto maximum of 16 cycles.

Pemetrexed Maintenance in Patients With Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy

A Prospective Randomized Phase III Trial of Maintenance Pemetrexed Versus Observation in Patients With Recurrent or Metastatic Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy Without Disease Progression

Time between randomization and disease progression or death from any causes, whichever came first. Alive patients free of progression will be censored at the last follow-up

Objective response rate will be measured according to RECIST 1.1

Safety assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03

Time interval between randomization and death (all causes). Alive patients will be censored at the last date of news or data cut off

QoL will be assessed by EORTC QLQ-C30 core questionaire

Korean Cancer Study Group

Asan Medical Center

Associated Professor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Carboplatin/Pralatrexate in Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer	NCT01188876	Ovarian Cancer Fallopian Tube ... Peritoneal Canc...	carboplatin pralatrexate Folic Acid Vitamin B12 Inj...	18 Years -	Massachusetts General Hospital
Pemetrexed Maintenance in Patients With Urothelial Carcinoma Who Completed First Line Platinum-based Chemotherapy	NCT03193788	Bladder Cancer Ureter Cancer Transitional Ce...	pemetrexed Folic Acid Vitamin B12 Inj... Dexamethasone	20 Years -	Asan Medical Center

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