A Study of CRLX101(NLG207) in Combination With Weekly Paclitaxel in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Ovarian Cancer Clinical Trial

Official title:

A Phase Ib/II Study of CRLX101 in Combination With Weekly Paclitaxel in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02389985
• Other study ID #: CRLX101-209
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: July 2015
• Est. completion date: October 18, 2018

Study information

• Verified date: May 2020
• Source: Lumos Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to estimate the maximum tolerated doses (MTD) of CRLX101 when administered in combination with weekly paclitaxel in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer.

Determine through pharmacokinetic evaluation(sometimes described as what the body does to a drug, refers to the movement of drug into, through and out of the body-the time and course of its absorption, bioavailability, distribution, metabolism, and excretion) whether or not the disposition of paclitaxel is affected by the concurrent administration of CRLX101.

Description:

Recurrent ovarian cancer represents a therapeutic challenge. Patients with resistant disease, showing progression within six months of platinum-containing therapy, have a poor prognosis, with median overall survival (OS) approximately 12 months.Ultimately most patients with recurrent disease ultimately develop platinum resistance, and novel strategies are needed.

In this setting the most active agents are pegylated liposomal doxorubicin (PLD), paclitaxel and topotecan. Multiple trials have demonstrated that combination therapy produces increased toxicity without improved efficacy.

This study proposes to examine the combination of CRLX101 in combination with weekly paclitaxel. Preclinical studies show synergistic activity in the SKOV3 human ovarian cancer xenograft ovarian cancer cell lines (14), as well as in vivo (15,16), perhaps via an antiangiogenic mechanism.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: October 18, 2018
• Est. primary completion date: June 4, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Histologic documentation of the original primary tumor is required via the pathology report.

2. Patient must have measurable disease or detectable (non-measurable) disease:

Measurable disease will be defined by RECIST 1.1.

3. Patients must have adequate bone marrow, renal, hepatic, and neurologic functions

4. Patients should be free of active infection requiring parenteral antibiotics.

5. Any other prior therapy directed at the malignant tumor, including chemotherapy, bevacizumab or other biologic or targeted agents and immunologic agents, must be discontinued at least 21 days (three weeks) prior to registration.

6. Any prior radiation therapy must be discontinued at least four weeks prior to registration.

7. Major surgery within 28 days (four weeks) prior to registration.

8. Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease.

9. Patients must have a GOG performance status of 0 or 1.

10. Patients who will be enrolled under protocol amendment # 2 must have previously received bevacizumab, either discontinued due to intolerability, or progressed after at least 2 cycles of bevacizumab

Exclusion Criteria:

1. Patients who have had previous treatment with:

• CRLX101 or with any topoisomerase I therapy;

• Weekly paclitaxel for recurrent or persistent disease.

2. Patients with a history of other invasive malignancies, with the exception of non-melanoma skin, are excluded if:

• There is any evidence of other malignancy being present within the last three years;

• Previous cancer treatment contraindicates this protocol therapy.

3. Patients with known active hepatitis or HIV.

4. Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first dose of study drug.

5. Patients with clinically significant cardiovascular disease.

6. Patients with serous non-healing wound, ulcer, or bone fracture.

7. Patients with active bleeding or pathologic conditions that carry high risk of bleeding

8. Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition.

9. Patients with active infection requiring parenteral antibiotics.

Related Conditions & MeSH terms

• Ovarian Cancer

Intervention

Drug:
• CRLX101

• Paclitaxel

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	The Ohio State University	Columbus	Ohio
United States	University of Oklahoma / Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	Washington University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
NewLink Genetics Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	2. To assess the overall safety and tolerability of CRLX101 in combination with weekly paclitaxel.	AEs, changes in clinical status, vital signs, and laboratory data	6 months
Other	To assess the anti-tumor activity of CRLX101 when administered concomitantly with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian fallopian tube or primary peritoneal cancer.	PFS per RECIST 1.1 with scans every 2 cycles	6 months
Primary	1. To estimate the maximum tolerated doses (MTD) of CRLX101 when administered in combination with weekly paclitaxel in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer.	The highest dose with <2 patients with DLTs out of 6 DLT-evaluable patients	6 months
Secondary	Comparison of pharmacokinetic perimeters including max concentration (Cmax), time to maximum concentration (Tmax), AUC, elimination half-life for CRLX101 and paclitaxel	PK	6 months