Panitumumab and Gemcitabine in Relapsed Ovarian Cancer (PanGem)

A Phase II Evaluation of Panitumumab and Gemcitabine as Treatment for Women With Recurrent Epithelial Ovarian Cancer.

This is a study to find out if the study drug, panitumumab, when given with gemcitabine works in treating ovarian cancer and to find out what side effects occur when they are given together.

Study Overview

• Status: Terminated
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer
• Intervention / Treatment: Biological: Panitumumab

Detailed Description

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality in women, with more than 22,000 deaths per year in the United States alone. Due to the lack of effective screening strategies and subtle early symptoms, eighty percent of newly diagnosed patients have disease that is advanced. Despite cytoreductive surgery and adjuvant paclitaxel-based and platinum-based chemotherapy, 5-year survival rates continue to be less than 40%. For patients who become resistant to the platinum compounds (defined as progressive disease while on a platinum-based chemotherapy regimen (refractory) or within 6 months of completing a platinum-based chemotherapy regimen (resistant)),the outlook is particularly poor, and often heralds multi-drug resistant disease.

At the present time, the management of ovarian cancer in the platinum refractory disease state is limited to palliative intent. Patients with advanced, bulky tumors, poor performance status and nutritional compromise are unlikely to respond to therapy and may be best served by supportive care. The clinical management of refractory disease requires both patience and persistence. A patient with platinum refractory disease is begun on one of the agents with activity and an evaluation of response is made every 6-8 weeks of therapy. As long as the patient shows no signs of disease progression, the therapy can be continued unless there is unacceptable toxicity. When progressive disease is observed, another of the list of available agents can be used. It is likely that patients will receive multiple single agents during the chronic phase of their illness. Every effort should be made to balance disease response with toxicity and quality of life.

Based on this rational, this trial will be conducted to evaluate the safety and efficacy of panitumumab, a human antibody targeted to the EGF-R, and Gemcitabine, in treating women with recurrent platinum-refractory/resistant EOC. Our aim is to determine the safety and feasibility of gemcitabine and panitumumab therapy in this population and once completed, to proceed with an efficacy study using an expanded cohort.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women & Infants' Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of metastatic, advanced, or recurrent platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancer.
• Prior first line therapy with a platinum and taxane based combination as adjuvant therapy
• Measurable disease defined by RECIST criteria
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• age > 18
• Karnofsky performance status > 70
• Up to three prior lines of cytotoxic therapy in the setting of recurrent disease.
• Estimated life expectancy of at least 3 months
• Women of child-bearing potential must have a negative pregnancy test

• Adequate hematopoietic function defined as:

  • ANC ≥ 1500/mm3
  • Platelets ≥ 100,000/mm3
  • Hemoglobin ≥ 9 g/dL
  • Magnesium ≥ lower limit of normal
  • Calcium ≥ lower limit of normal

• Adequate renal and hepatic function defined as:

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT ≤ 3 times ULN
  • Alanine aminotransferase (ALT) ≤3xULN (if liver metastases ≤5xULN)
  • Alkaline phosphatase ≤ 3 times ULN
  • Creatinine ≤ 1.5 mg/dL times ULN
  • Creatinine clearance ≤ 50 mL/min

Exclusion Criteria:

• Prior anti-EGFr antibody therapy (e.g., cetuximab) or treatment with small molecule EGFr inhibitors (e.g., gefitinib, erlotinib, lapatinib)
• Prior treatment with gemcitabine
• Radiotherapy ≤ 14 days prior to enrollment.
• More than three lines of systemic chemotherapy for recurrent or advanced disease. Prior hormonal therapy is allowed.
• Prior immunotherapy, or experimental or approved proteins/antibodies
• Female subject is pregnant or breast-feeding.
• Patient has received other investigational drugs within 28 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Prior treatment with panitumumab
• Concurrent uncontrolled illness
• Ongoing or active infection
• History or active secondary cancer within the last 5 years, except for superficial basal cell skin cancers, curatively resected non-melanoma skin cancer
• Psychiatric illness or social situation that would preclude study compliance.
• History or known presence of central nervous system (CNS) metastasis
• Subjects requiring chronic use of immunosuppressive agents (e.g., methotrexate, cyclosporine)
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) < 1 year before randomization
• History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan
• Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection
• Major surgery within 28 days or minor surgery within 14 days of study enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panitumumab and Gemcitabine	Biological: Panitumumab; Panitumumab 2.5 mg/kg on D1, D8, D15, and D22 and Gemcitabine 800 mg/m2 on D1, D8, and D15 of each 28 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate, Measured by RECIST Criteria	Documentation of known measurable or evaluable disease parameters after every 2 cycles of treatment. If any patient is withdrawn for the study prior to completion of therapy a repeat evaluation will be done at that time.	Every 8 weeks while on-study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events, Measured by Active Version of the NCI Common Toxicity Criteria	Adverse events (AEs) will be recorded during the duration of the trial, whether or not the events are considered related to medication. All AEs considered to be related to trial therapy will be followed for resolution, including into the post-treatment period.	Every 4 weeks while on-study, up to 24 weeks

Collaborators and Investigators

• Sponsor: Women and Infants Hospital of Rhode Island
• Collaborators: Amgen
• Investigators: Principal Investigator: Carolyn McCourt, MD, Women & Infants' Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: February 9, 2011
• First Submitted That Met QC Criteria: February 11, 2011
• First Posted (Estimate): February 15, 2011

Study Record Updates

• Last Update Posted (Estimate): August 25, 2015
• Last Update Submitted That Met QC Criteria: July 28, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: recurrent ovarian cancer; platinum-refractory ovarian cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Antineoplastic Agents; Antineoplastic Agents, Immunological; Panitumumab
• Other Study ID Numbers: WIH 20050782