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

NCT01188876 | Completed Phase 1 Results DMC

• 1 other identifier: 10-113
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Keywords

carboplatin; recurrent; platinum sensitive; pralatrexate

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  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.

  1 year

• Best Overall Response

  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

  1 Year

Secondary Outcomes (5)

• Overall Survival

  6, 12, 18, and 24 months

• Progression Free Survival

  3 months, 6 months

• Treatment Related Adverse Events

  1 Year

• Maximum Concentration of Drug in Plasma (Cmax)

  Day 1 and Day 15

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

  Day 1 and Day 15

Study Arms (1)

Carboplatin/Pralatrexate

EXPERIMENTAL

Drug: carboplatin; Drug: pralatrexate; Drug: Folic Acid; Drug: Vitamin B12 Injection

Interventions

carboplatin DRUG

Given intravenously on Day 1 of each 28-day cycle

Carboplatin/Pralatrexate

pralatrexate DRUG

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

Carboplatin/Pralatrexate

Folic Acid DRUG

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.

Carboplatin/Pralatrexate

Vitamin B12 Injection DRUG

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.

Carboplatin/Pralatrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be diagnosed with a platinum-sensitive recurrence of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
• The following histologic subtypes are eligible: papillary serous, endometrioid, mucinous, clear cell, adenocarcinomas, transitional, and mixtures of the above.
• Patients must have at least one measurable lesion according to RECIST criteria via CT or MRI scan. CT of the chest should be performed if any known disease is present in the chest. Pleural effusions, ascites, bone metastases, CA125 tumor markers, and lesions located in previously radiated areas are not considered measurable.
• Patients must have received a platinum-containing regimen at initial diagnosis.
• ECOG Performance Status of 0, 1 or 2
• Patients may have received up to 2 prior chemotherapy regimens in the recurrent cancer setting
• years of age or older
• Life expectancy of greater than 12 weeks
• Baseline laboratory values must meet what is outlined in the protocol
• Patients must receive vitamin B12 and folic acid prior to starting treatment
• Complete recovery from previous chemotherapy or biologic therapy
• During the Phase II of the study, patients with significant ascites and/or pleural effusions will undergo consideration of drainage of these areas prior to starting carboplatin and pralatrexate.
• Women of childbearing potential must have a negative pregnancy test within 7 days prior to initiating chemotherapy on trial and must agree to practice effective method of birth control during the study and for six months after their last treatment.
• Patients must have a normal QTc interval

You may not qualify if:

• Prior pelvic radiotherapy to greater than 25% of bone marrow
• Any uncontrolled medical problem that in the opinion of the investigator would preclude safe administration of the study drugs.
• Past history of bone marrow transplantation or stem cell support
• Patient with known history of CNS metastasis is ineligible unless the patient has had treatment with surgery or radiation therapy, is neurologically stable, and does not require oral or intravenous corticosteroids or anticonvulsants.
• A history of prior malignancy except for adequately treated carcinoma in situ of the uterine cervix, incidental stage I endometrial cancer, basal cell or squamous cell skin cancer, or breast cancer (invasive or ductal carcinoma in situ) for which the patient has been disease-free for at least three years.
• Routine prophylactic use of G-CSF or GM-CSF within two weeks prior to study entry.
• Clinically significant cardiac disease
• Uncontrolled hypercalcemia or diabetes mellitus
• Any signs of intestinal obstruction that interfere with bowel function and/or nutrition
• Grade 2 or greater peripheral neuropathy
• Participation in an investigational study within three weeks prior to study entry.
• History of anaphylactic shock to prior platinum chemotherapy that would preclude safe administration of study carboplatin.
• History of psychiatric disability or other central nervous system disorder as judged by the principal investigator that would be considered significant and that would preclude informed consent, safe administration of study medications and affecting ability to comply with study procedures.
• Doses of ibuprofen in excess of 400mg QID.
• Interval cytoreductive surgery planned for while subject is on-study.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• Brigham and Women's Hospital: collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Recurrence

Interventions

Carboplatin; 10-propargyl-10-deazaaminopterin; Folic Acid; Vitamin B 12

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Marcela del Carmen, MD, MPH
• Organization: Massachusetts General Hospital

MDELCARMEN@mgh.harvard.edu

617-724-4800

Study Officials

• Marcela G. del Carmen, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MPH

Study Record Dates

• First Submitted: August 24, 2010
• First Posted: August 26, 2010
• Study Start: August 1, 2010
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2017
• Last Updated: January 19, 2018
• Results First Posted: January 19, 2018

Record last verified: 2017-12

Locations

US (2)