Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Camptothecin

CRLX101 is administered at 15mg/m2 IV every other week

CRLX101

Best Supportive Care

NewLink Genetics

The purpose of this study is to compare median overall survival of patients with advanced non-small cell lung cancer (NSCLC) treated with CRLX101 to patients treated with best supportive care (BSC).

Lung cancer remains the leading cause of cancer-related mortality in men and women worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer. The development of targeted therapies has changed the approach to treating NSCLC significantly over the past decade with targeted therapies generally possessing safety advantages over traditional cytotoxic regimens. However, combination paradigms and resistance patterns complicate the use of these agents. CRLX101 is a nanoparticle comprised of camptothecin (CPT) conjugated to a cyclodextrin-based polymer. CRLX101 is designed to increase the exposure of tumor cells to CPT while minimizing side effects.

A Phase 2 Study of CRLX101(NLG207) in Patients With Advanced Non-Small Cell Lung Cancer

A Randomized, Phase 2, Study to Assess the Safety and Activity of CRLX101, a Nanoparticle Formulation of Camptothecin, in Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed One or Two Previous Regimens of Chemotherapy

Comparison of survival among patients treated with CRLX101 + best supportive care vs patients treated wiht best supportive care only.

Comparison of objective response rate in subjects treated with CRLX101+BSC versus subjects treated with BSC alone.

NewLink Genetics Corporation

15 mg/m2 CRLX101 infused IV over 60 minutes every other week + Standard therapy consisting of best supportive care, including at least blood and platelet transfusions, therapeutic radiation, and bone marrow support (granulocyte colony-stimulating factor \[G-CSF\]) as required.

CRLX101+BSC

Standard therapy consisting of best supportive care, including at least blood and platelet transfusions, therapeutic radiation, and bone marrow support (granulocyte colony-stimulating factor \[G-CSF\]) as required.

Best Supportive Care (BSC) Only

15 mg/m2 CRLX101 infused IV over 60 minutes every other week + Standard therapy consisting of best supportive care (BSC), including at least blood and platelet transfusions, therapeutic radiation, and bone marrow support (granulocyte colony-stimulating factor \[G-CSF\]) as required.

CRLX101 + BSC (Best Supportive Care)

Standard therapy consisting of best supportive care (BSC), including at least blood and platelet transfusions, therapeutic radiation, and bone marrow support (granulocyte colony-stimulating factor \[G-CSF\]) as required.

BSC (Best Supportive Care) Alone

Total

Age, Continuous

Sex: Female, Male

Russian Federation

Ukraine

Region of Enrollment

Intention-to-treat (ITT) and Patient Safety Population (PSP), includes all CRLX101 + BSC subjects who received at least 1 dose of study treatment and all randomized BSC alone subjects who attended at least 1 study visit.

Adrian Senderowicz

CRLX101: CRLX101 is administered at 15mg/m2 IV every other week

Best Supportive Care: best supportive care

Intention-to-treat (ITT) and Patient Safety Population (PSP), includes all CRLX101 + BSC subjects who received at least 1 dose of study treatment and all randomized BSC alone subjects who attended at least 1 study visit. (Confidence interval if insufficient data to estimate NE = 99999.99)

To Compare Overall Survival of Patients Treated With CRLX101 + BSC to Those Patients Treated With BSC Only

Assess Objective Response Rate (ORR) of CRLX101+ BSC Compared to BSC Only

Overall Study

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Bevacizumab

Leucovorin

Fluorouracil

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

Subjects will receive weekly infusion of CRLX101 alone. Starting dose is 12 mg/m\^2 and the next dose level is 15 mg/m\^2 (or 10 mg/m\^2 if 12 mg/m\^2 is not well tolerated. No other dose levels will be explored.

Subjects receive weekly infusion of CRLX101 in combination with bi-weekly bevacizumab (10 mg/kg. The starting dose is 12 mg/m\^2 and the next dose level is 15 mg/m\^2. No other dose levels will be explored.

Subjects receive weekly infusion of CRLX101 for 3 of every 4 weeks in combination with bi-weekly mFOLFOX6 (oxaliplatin 85 mg/m\^2, leucovorin 400 mg/m\^2 and 5FU 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous infusion). The starting dose is 12 mg/m\^2 and the next dose level is 15 mg/m\^2.

infusion weekly CRLX101 + bevacizumab biweekly

infusion weekly CRLX101 for 3 or every 4 weeks and in combination with bi-weekly mFOLFOX6

mFOLFOX6

NewLink Ge

The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of weekly dosing of CRLX101 (both as monotherapy; (Schedule 1) and in combination with bevacizumab every 2 weeks (Schedule 2) and weekly with a 3 week on / 1 week off schedule in combination with mFOLFOX6 (Schedule 3) to affirm the dose for future clinical studies.

This is an open-label, dose escalation study. Subjects enrolled in Schedule 1 will receive weekly CRLX101 alone. The starting dose for Schedule 1 is 12 mg/m\^2 and the next dose level is 15 mg/m\^2 (or 10 mg/m\^2 if 12 mg/m\^2 is not well tolerated). No other dose levels in Schedule 1 will be explored.

Subjects enrolled in Schedule 2 will receive weekly CRLX101 in combination with bi-weekly bevacizumab (10 mg/kg) The starting dose for Schedule 2 is 12 mg/m\^ and the next dose is 15 mg/m\^2. No other dose levels in Schedule 2 will be explored

Subjects enrolled in Schedule 3 will receive weekly CRLX101 for 3 of every 4 weeks in combination with bi-weekly mFOLFOX6 (oxaliplatin 85 mg/m\^2, leucovorin 400 mg/m\^2 and 5FU (fluorouracil) 400 mg/m\^2 bolus followed by 2400 mg/m\^2 continuous infusion). The starting dose for Schedule 3 is 12 mg/m\^2 and the next dose is 15 mg/m\^2.

In the absence of dose-limiting toxicities (DLTs) additional subjects may be enrolled (expansion cohort) at the same, intermediate or lower dose levels following consultation between the Investigator and Sponsor.

Enrollment of 6-8 subjects will occur in each cohort for all 3 Schedules.

The MTD is defined as the highest dose level at which fewer than 2 out of 6 subjects experience a DLT. RP2D will be selected based on overall tolerability data from all subjects treated at different dose cohorts in this study.

No intra-patient dose escalation is allowed.

Approximately 61 evaluable subjects are anticipated to be enrolled: 15 subjects in Schedule 1, 15 subjects in Schedule 2 and approximately 31 subjects are anticipated in Schedule 3 (approximately 16 in the dose escalation cohort and up to 15 in the expansion cohort).

The exact number of subjects is dependent on the actual number of subjects enrolled per cohort and the number of cohorts investigated.

Alternative Dosing for CRLX101(NLG207) Alone, With Avastin and With mFOLFOX6 in Advanced Solid Tumors

Evaluation of an Alternative Schedule for CRLX101 Alone in Combination With Bevacizumab and in Combination With mFOLFOX6 in Subjects With Advanced Solid Tumor Malignancies

To determine the maximum tolerated dose (MTD) / recommended Phase 2 dose (RP2D) of CRLX101 when administered by intravenous (IV) infusion every week (QW) alone (Schedule 1), (QW) in combination with bevacizumab (Q2W) (Schedule 2) and weekly with a 3-week on / 1-week off schedule in combination with mFOLFOX6 (Q2W) (Schedule 3) in subjects with advanced solid tumor malignancies

Will be determined by reported AEs, SAEs, physical exam findings, vital sign measurements,12-lead ECG readings, clinical lab evaluations, and treatment discontinuation due to toxicity.

Urine samples will be collected to evaluate the urinary excretion of total and unconjugated drug before, during, and after infusion. PK parameters in urine will include the maximum concentration (Cmax), amount of drug in the urine, % of drug eliminated in the urine. PK parameters will be calculated using non-compartmental analysis. Actual sampling times will be used to calculate PK parameters in this study.

Plasma PK parameters will include clearance (CL) for both total and unconjugated drug.

The plasma PK parameters will include volume of distribution (Vd)

Plasma PK parameters will include half-life (t1/2)

Plasma PK parameters will include maximum concentration (Cmax)

Plasma PK parameters will include area under the concentration versus time curve (AUC)

To further explore preliminary signs of anti-tumor activity of CRLX101 when administered alone (Schedule 1) and in combination with bevacizumab (Schedule 2), and in combination with mFOLFOX6 (Schedule 3)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Kennedy Disease

Androgens

Androgen Receptor Antagonists

Combination treatment of increasing dose of CRLX101 (formerly IT-101) with enzalutamide

Tolerable dose of CRLX101 (formerly IT-101) in combination with enzalutamide (8 participants, expandable to 21 total participants)

enzalutamide is an androgen receptor (AR) antagonist that is standard care therapy for metastatic prostate cancer

enzalutamide

CRLX101 is a nanoparticle-drug conjugate (NDC) comprised of a linear cyclodextrin-polyethylene glycol-base polymer conjugated to multiple 2 (S)-camptothecin (CPT) molecules (Poly-CD-PEG-Camptothecin)

Ravi A Madan, M.D.

Background:

Some prostate cancer keeps growing even when testosterone in the body drops to very low levels. This is called castrate-resistant prostate cancer. One treatment is enzalutamide. This is a modern hormonal therapy. But it only works for a certain amount of time and then the cancer becomes resistant to it. Researchers want to see if adding the treatment CRLX101 (formerly IT-101) could make enzalutamide work again for people who have already had it.

Objective:

To test a new way of treating prostate cancer using CRLX101 plus enzalutamide in people with certain prostate cancer who already had enzalutamide treatment.

Eligibility:

Adults ages 18 years and older with metastatic, castration-resistant prostate cancer who have had enzalutamide treatment

Design:

Participants will be screened with a medical history and physical exam. They will have blood and urine tests. They will have a scan of the chest/abdomen/pelvis. They will have a bone scan.

Participants will get treatment in cycles. A cycle lasts 28 days. They will take enzalutamide by mouth once a day. They will get CRLX101 through an intravenous (IV) every 1 or 2 weeks.

Participants will repeat screening tests throughout the study.

Participants will have a follow-up visit 3-4 weeks after they stop taking the study drug. They will repeat most screening tests and have an electrocardiogram.

Background:

* Enzalutamide is established as first-line hormonal therapy in participants with metastatic castration resistant prostate cancer (mCRPC). However, it is increasingly recognized that acquired resistance to therapy (e.g., androgen receptor (AR) overexpression, androgen receptor variant 7 (AR-V7) could limit the durability of response to therapy
* Upregulation of Hypoxia-inducible factor 1-alpha (HIF-1Alpha) in hypoxic tumor cells provides a mechanism of acquired resistance to current hormonal therapies and chemotherapies. Acquired resistance increases angiogenesis and metastasis, leading to disease progression
* Targeting the hypoxia driven tumor microenvironment (e.g., down-regulation of HIF-1Alpha) in addition to the androgen receptor (e.g., enzalutamide) has synergistic activity against prostate cancer cell line models (e.g., LNCaP, 22Rv1).
* CRLX101 is a nanoparticle drug conjugate composed of 20(S)-camptothecin (a potent and highly selective topoisomerase I inhibitor with anti-HIF-1Alpha properties) conjugated to a linear, cyclodextrin-polyethylene glycol-based polymer
* CRLX101 has been shown to be safe, tolerable, and efficacious in numerous Phase II clinical investigations in a variety of tumor subtypes.
* Preclinical and clinical studies have shown CRLX101 significantly down-regulates HIF-1alpha, impacting tumor-driven angiogenesis.
* The treatment combination of CRLX101 and enzalutamide provides a reasonable approach to re-sensitizing prostate cancer cells to hormonal therapy via synergistic antitumor activity and inhibition of acquired resistance

Objectives:

-Primary Objective: To evaluate the anti-tumor activity of CRLX101 at the recommended phase II dose (RP2D) in combination with enzalutamide with respect to treatment response, defined as greater than or equal to 50% PSA decline or stable disease on imaging following 5 months of treatment.

Eligibility:

* Patients must have progressive mCRPC per Prostate Cancer Working Group 3(PCWG3)
* Patients must be at least 18 years of age and able to give informed consent
* Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2
* Evaluable metastatic disease on bone scan or measurable disease on computed tomography (CT) Scan per PCWG3 and/or Response Evaluation Criteria in Solid Tumors (RECIST)
* Patients must have had disease progression while receiving prior enzalutamide treatment

Design:

* The study will be conducted using an optimal two stage Phase II design (8 participants, expandable to 21 participants total) aimed to determine the percentage of participants with a prostate-specific antigen (PSA) decline of greater than 50% or stable disease at 5 months.
* The first 3 to 6 participants enrolled on study will follow a lead-in dosing scheme to confirm the safety of the combination (CRLX101 12 mg/m(2) every 2 weeks for the first two cycles, followed by CRLX101 15 mg/m(2) every 2 weeks at the start of cycle 3, with enzalutamide 160 mg administered once daily starting on cycle 1 day 2) prior to initiation of the optimal two stage study design.
* For participants enrolled on study following the lead-in, the confirmed tolerable dose of CRLX101 will be administered via intravenous (IV) infusion every 2 weeks. Enzalutamide 160 mg will be administered orally once daily beginning on cycle 1 day 2.
* Blood and urine will be collected at multiple time points for pharmacokinetic (PK) and pharmacodynamic (PD0 analyses.
* Tumor assessments will be made using Technetium-99 (99Tc) bone scintigraphy and/or CT scan (chest, abdomen, and pelvis) at baseline, prior to Cycle 3 and every 3 cycles thereafter.
* The accrual ceiling for the study is set at 30 participants.

Combining CRLX101, a Nanoparticle Camptothecin, With Enzalutamide in People With Progressive Metastatic Castration Resistant Prostate Cancer Following Prior Enzalutamide Treatment

A Single Arm Phase II Study Combining CRLX101, a Nanoparticle Camptothecin, With Enzalutamide in Patients With Progressive Metastatic Castration Resistant Prostate Cancer Following Prior Enzalutamide Treatment

All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

All collected IPD will be shared with collaborators under the terms of collaborative agreements.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Anti-tumor activity is \>=50% prostate-specific antigen (PSA) decline or stable disease on imaging following 5 months of treatment in participants with progressive metastatic castration resistant prostate cancer (mCRPC) following enzalutamide treatment. Stable disease (SD) is neither sufficient shrinkage to qualify for partial response (at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters) nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study).

Proportion of participants with a sustained \>30% decline in prostate-specific antigen (PSA) from baseline based on all evaluable participants.

OS is defined as the duration of time from the start of treatment to the time of death estimated based on all evaluable participants.

Number of participants with a change in measurable disease as determined by RECIST. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

Number of participants with a change in measurable disease as determined by the Prostate Cancer Working Group 3 (PCWG3). PSA values will be captured at each visit and PSA declines and progression (by radiographic evidence or clinical symptoms) will be followed. Radiographic disease progression is considered if a minimum of two new lesions is observed on bone scan. Clinical disease progression is the need for chemotherapy or other change in therapy based on increased cancer related symptoms.

National Cancer Institute (NCI)

Principal Investigator

Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+

1/Lead-In Safety: CRLX101 With Enzalutamide

Age, Categorical

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Normal PSA is variable. Higher above the normal range often means more cancer.

Median Prostate-Specific Antigen (PSA)

Prior lines of therapy refers to the multiple lines of treatment given to a participant for their disease. First treatment, second treatment, third treatment, and so forth.

Median Prior Lines of Therapy

Dr. Ravi Madan

>=50% prostate-specific antigen (PSA) decline

Stable Disease

Percentage of Participants With Anti-tumor Activity

Proportion of Participants With a Sustained >30% Decline in Prostate-specific Antigen (PSA)

3/4 participants were analyzed because one participant was lost to follow-up.

Overall Survival (OS)

Lead-in Dosing: CRLX101 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+

Number of Participants With a Change in Measurable Disease From Baseline as Determined by Response Evaluation Criteria in Solid Tumors (RECIST)

Number of Participants With a Change in Measurable Disease as Determined by the Prostate Cancer Working Group 3 (PCWG3)

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

Tolerable dose of CRLX101 (formerly IT-101) in combination with enzalutamide (8 participants, expandable to 21 total participants)

enzalutamide: enzalutamide is an androgen receptor (AR) antagonist that is standard care therapy for metastatic prostate cancer

CRLX101: CRLX101 is a nanoparticle-drug conjugate (NDC) comprised of a linear cyclodextrin-polyethylene glycol-base polymer conjugated to multiple 2 (S)-camptothecin (CPT) molecules (Poly-CD-PEG-Camptothecin)

2/Efficacy: CRLX101 With Enzalutamide

Symptoms and General Pathology

Gland and Hormone Related Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

CRLX101 and weekly paclitaxel administered by IV on days 1 and 15 of a 28 day cycle. Paclitaxel only is administered by IV on day 8.

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.

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.

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

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

AEs, changes in clinical status, vital signs, and laboratory data

PFS per RECIST 1.1 with scans every 2 cycles

The highest dose with \<2 patients with DLTs out of 6 DLT-evaluable patients

Digestive System Diseases

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Fallopian Tube Cancer

Richard Penson, MD, MRCP

This research study is a Phase II clinical trial. In addition to studying safety, Phase II clinical trials test if the investigational drug is effective and whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved CRLX101 for your type of cancer.

Camptothecin is a chemical extracted from plants that is the basis for the standard FDA-approved chemotherapy drugs irinotecan and topotecan. Camptothecin works by interfering with the way cells divide and multiply. The investigational drug CRLX101 is a formulation of camptothecin and a large molecule (nanoparticle)that appears to allow more of the camptothecin to get into tumors and stay in tumors. The persistence of the CRLX101 in the tumor may increase the probability that the tumor cells will be damaged.

CRLX101 has been well tolerated in the laboratory and in participants with different kinds of cancer.

Bevacizumab (Avastin) is a VEGF inhibitor which has activity in many kinds of cancer. Bevacizumab has been successfully combined with many chemotherapy partners.

It has been hypothesized that the combination of bevacizumab with CRLX101 might have unique clinical activity in combination in the treatment of this disease due to the simultaneous inhibition of distinct steps along the HIF → (CAIX) → VEGF → VEGFR2 pathway. Specifically, it is hypothesized that CRLX101-mediated inhibition of HIF-1α carries with it the potential to interrupt hypoxia and HIF-1α-associated resistance to VEGFR inhibitors. It is hoped that this combination will work to treat your type of cancer.

You will receive CRLX101 and bevacizumab through an intravenous (IV) infusion once every 14 days. Each cycle is 28 days. You will continue to receive both drugs until you and/or the research doctor decides it may not be in your best interest to continue.

You will receive premedication including decadron, zantac and benadryl to help prevent an allergic reaction and nausea prior to your CRLX101 infusion.You will also receive IV fluid before and after the study drug administration to keep you hydrated. It will be important for you to drink water regularly in between study visits.You will be treated as an outpatient. At every clinic visit, you will undergo the following assessments: Medical history, physical examination, vital signs, performance status, routine blood tests, urine tests, assessment for any new side effects, CT evaluation (every 8 weeks).

You will have an end of study visit within 30 days of your last dose.

CRLX101 in Combination With Bevacizumab for Recurrent Ovarian/Tubal/Peritoneal Cancer

A Phase II, 2-stage Trial of CRLX101 in Combination With Bevacizumab in Recurrent Platinum-Resistant Ovarian, Tubal and Peritoneal Cancer

Progression free survival at 6 months (PFS6) using RECIST 1.1

Analysis of ovarian tumor biopsies and ascites of the presence or absence of CRLX101 or the active drug, camptothecin

Massachusetts General Hospital

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Rectal Diseases

Herbal and Botanical

Capecitabine

Antimetabolites

Cola

During Phase Ib, we will evaluate the safety and determine the MTD/RP2D of CRLX101 + capecitabine (Cape) and radiation therapy (XRT) in patients with rectal cancer using the traditional 3+3 dose escalation design. Adverse events (AEs) will be evaluated via the CTCAE version 4.0. Patients in Phase Ib will also be followed for pathological response if they have resectable disease.

In Phase II, CRLX101 will be administered at the RP2D in combination with capecitabine and radiation in patients with locally advanced rectal cancer for a total of 5-6 weeks, depending on the total radiation dose. A total of 3 doses of CRLX101 will be administered every other week. Surgery will take place at least 6 weeks after the completion of chemoradiotherapy.

CRLX101 is an experimental nanoparticle formulation of the anticancer agent camptothecin manufactured by Cerulean Pharma Inc..

Capecitabine is an oral fluoropyrimidine pro-drug, metabolically converted to 5-fluorouracil after administration. It is indicated as adjuvant treatment in patients with stage III colorectal cancer (Dukes' C colon cancer), and as first-line treatment of metastatic colorectal cancer.

This protocol allows physician discretion as to the use of Intensity Modulated Radiation Therapy (IMRT) or 3D conformal planning techniques.

Radiation begins on Day1 of neoadjuvant chemotherapy and continues for 28 (if \<T4) or 30 (T4 disease) consecutive weekdays. Patient will receive 1.8 Gy daily fractions of radiotherapy without a break except for weekends and holidays.

Dose is to be prescribed to an isodose surface that encompasses the planning target volume (PTV) and that satisfies the dose uniformity guidelines below. The minimum dose to PTV 1 and PTV 2 shall be no less than 95% of the protocol specified dose for that volume.

Radiotherapy

Surgery will take place at least 6 weeks post completion of chemoradiotherapy in patients with resectable disease; tissue from surgical resection will be preserved for correlative studies in those patients who do not achieve a pCR.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 2 Study of CRLX101(NLG207) in Patients With Advanced Non-Small Cell Lung Cancer	NCT01380769	Non-Small Cell ...	CRLX101 Best Supportive...	18 Years -	Lumos Pharma
Alternative Dosing for CRLX101(NLG207) Alone, With Avastin and With mFOLFOX6 in Advanced Solid Tumors	NCT02648711	Solid Tumors	CRLX101 Bevacizumab mFOLFOX6	18 Years -	Lumos Pharma
Alternative Dosing for CRLX101(NLG207) Alone, With Avastin and With mFOLFOX6 in Advanced Solid Tumors	NCT02648711	Solid Tumors	CRLX101 Bevacizumab mFOLFOX6	18 Years -	Lumos Pharma
Combining CRLX101, a Nanoparticle Camptothecin, With Enzalutamide in People With Progressive Metastatic Castration Resistant Prostate Cancer Following Prior Enzalutamide Treatment	NCT03531827	Metastatic Cast... Prostate Neopla...	enzalutamide CRLX101	18 Years -	National Institutes of Health Clinical Center (CC)
A Study of CRLX101(NLG207) in Combination With Weekly Paclitaxel in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer	NCT02389985	Ovarian Cancer	CRLX101 Paclitaxel	18 Years -	Lumos Pharma
CRLX101 in Combination With Bevacizumab for Recurrent Ovarian/Tubal/Peritoneal Cancer	NCT01652079	Ovarian Cancer Fallopian Tube ... Primary Periton...	CRLX101	18 Years -	Massachusetts General Hospital
Neoadjuvant Chemoradiotherapy With CRLX-101 and Capecitabine for Rectal Cancer	NCT02010567	Rectal Cancer	CRLX101 Capecitabine Radiotherapy Surgery	18 Years -	UNC Lineberger Comprehensive Cancer Center

Spots Global Cancer Trial Database for crlx101

Every month we try and update this database with for crlx101 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for crlx101

Every month we try and update this database with for crlx101 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for crlx101 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.