Dose-Finding, Safety and Efficacy Study of RX-0201 Plus Everolimus in Metastatic Renal Cell Cancer

• Sponsor: Rexahn Pharmaceuticals, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02089334
• Collaborator: (none)
• Enrollment: 24
• Locations: 7
• Arm: 1
• Actual Duration (Months): 45.5
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the maximum tolerated dose of RX-0201, up to a target dose of 250 mg/m^2/day, when given in combination with everolimus (Stage 1), and to assess the safety and efficacy of RX-0201 plus everolimus, in subjects with metastatic renal cell cancer (Stage 2).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Cancer	Drug: RX-0201	Phase 1/Phase 2

Detailed Description

This multi-center, open-label, randomized, parallel group study of RX-0201 in combination with everolimus, versus everolimus alone to treat subjects with advanced renal cell carcinoma will be conducted in 2 stages. Stage 1 will be an open-label, dose-escalation study of RX-0201 to identify a safe and tolerable dose of RX-0201 up to a target dose of 250 mg/m^2/day when given in combination with everolimus. Stage 2 will be a randomized, open-label, 2-arm study of RX-0201 in combination with everolimus versus everolimus alone. Subjects will receive RX-0201, at the dose identified in Stage 1, in combination with everolimus or everolimus alone, for up to 8 cycles to determine safety and efficacy of the combination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label, Phase 1b/2 Study to Evaluate the Safety and Efficacy of RX-0201 in Combination With Everolimus to Treat Subjects With Advanced Renal Cell Carcinoma
• Actual Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: Apr 26, 2018
• Actual Study Completion Date: May 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RX-0201 plus everolimus (Stage 1 & 2) RX-0201 and everolimus will be taken together as described in the Interventions description.	Drug: RX-0201; RX-0201 will be administered in a dose up to 250mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. In Stage 2, RX-0201 will be administered the dose determined in Stage 1 as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles.; Other Names: Archexin

Outcome Measures

Primary Outcome Measures

1. Incidence of Dose-limiting Toxicities (DLTs) (Stage 1) [after 1 cycle (3 weeks) of treatment with RX-0201 and everolimus]

   Incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities

2. Progression Free Survival (Stage 2) [4 months of treatment with RX-0201 and everolimus]

   Median PFS. Progression determined by RECIST v1.1

Secondary Outcome Measures

1. Steady State Concentration (Css) of RX-0201 (Stage 1) [predose, 1, 2, 3, 4, 6, and 24 hours after start of Cycle 1 RX-0201 infusion, and then immediately prior to the end of Cycle 1 infusion (Day 15), 1, 2, 3, 4, 6, and 24 hours after infusion is stopped]

   Css of RX-0201 at the beginning and end of the 14 day continuous infusion

2. Incidence of Adverse Events, Changes in Clinical Laboratory Tests and Vital Signs Over Time (Stage 1 and Stage 2) [up to 24 weeks of treatment with RX-0201 plus everolimus and at least 30 days of safety follow up]

   safety of RX-0201 was evaluated through reporting using the grading system in the CTCAE version 4.03 for adverse events and laboratory abnormalities. All statistical methods for safety were descriptive in nature.

3. Best Overall Response as Determined by RECIST v1.1. [Baseline and at weeks 6, 12, 18, and 24]

   Best overall response as determined by RECIST v1.1. Not Evaluable included the subjects who had completed at least one treatment cycle but no overall response evaluation. Not Done included the subjects who dropped out from the study without completing any treatment cycle and overall response evaluation. The best overall response for each subject from all post-baseline time point overall responses was used. The best overall response was the best response recorded from the start of the treatment until disease progression/recurrence, or occurrence of intolerable toxicity, whatever came first.

Other Outcome Measures

1. Biomarker Concentrations in Blood [Baseline and at weeks 6, 12, 18, and 24]

   Exploratory analysis of AKT pathway biomarkers, tumor apoptosis biomarkers and other biomarkers in blood or tumor samples

2. RX-0201 Concentration in the Blood (Stage 2 Only) [After 2 weeks of treatment]

   Exploratory analysis of plasma concentrations of RX-0201 at the end of infusion

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females ≥ 18 years of age at screening

• Histological or cytological diagnosis of renal cell cancer with a clear-cell component

• Measurable or evaluable disease defined by Response Evaluation Criteria for Solid Tumors (RECIST) ver. 1.1

• Must have received at least one course of therapy with a VEGFR-targeting tyrosine kinase inhibitor (eg, sorafenib, sunitinib, axitinib, pazopanib or tivozanib) and progressed within 6 months of planned first dose of study treatment

• ECOG performance status of 0,1 or 2

• Life expectancy > 3 months

• Provide written informed consent

Exclusion Criteria:

• Brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before planned first dose of study drug

• Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before planned first dose of study drug. Systemic treatment with radionuclides within 6 weeks before planned first dose of study drug. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible

• Prior treatment with everolimus, or any other specific or selective TORC1/PI3K/AKT inhibitor (eg, temsirolimus)

• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before planned first dose of study drug

• Receipt of any type of anticancer antibody (including investigational antibody) within 4 weeks before planned first dose of study drug

• Taking strong inducers or inhibitors of CYP450s for subjects receiving everolimus

• Chronic treatment with corticosteroids or other immunosuppressive agents

• Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors

• Subjects with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients

• Major surgery within 2 months before planned first dose of study drug

• Myocardial infarction within the previous 6 months before planned first dose of study drug

• Active infection requiring parenteral antibiotics within 2 weeks before planned first dose of study drug

• Diagnosis of another malignancy within 2 years before planned first dose of study drug, except for superficial skin cancers, or localized, low grade tumors

• Prior or current history of hepatitis B, hepatitis C or human immunodeficiency virus

• Sexually active fertile subjects (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 30 days after the last dose of study treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rexahn Site	Tucson	Arizona	United States	85719
2	Rexahn Site	Duarte	California	United States	91010
3	Rexahn Site	Albuquerque	New Mexico	United States	87106
4	Rexahn Site	Bronx	New York	United States	10467
5	Rexahn Site	New York	New York	United States	10065
6	Rexahn Site	Salt Lake City	Utah	United States	84112
7	Rexahn Site	Seattle	Washington	United States	98101

Sponsors and Collaborators

• Rexahn Pharmaceuticals, Inc.

Investigators

• Study Director: Ely Benaim, MD, Rexahn Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Study Protocol - Mar 8, 2017
• Statistical Analysis Plan - Dec 7, 2018

More Information

Publications

None provided.

• Responsible Party: Rexahn Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02089334
• Other Study ID Numbers: RX-0201-P2-A-09
• First Posted: Mar 17, 2014
• Last Update Posted: Jun 30, 2020
• Last Verified: Jun 1, 2020

• Keywords provided by Rexahn Pharmaceuticals, Inc.: renal cell carcinoma; clear cell; renal cancer; metastatic renal cancer; Carcinoma, Renal Cell*/therapy; Humans; Kidney Neoplasms*/therapy
• Additional relevant MeSH terms: Carcinoma, Renal Cell

Study Results

Participant Flow

Arm/Group Title	125 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	200 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	250 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	250 mg/m^2/Day RX-0201 + Everolimus (Stage 2)
Arm/Group Description	RX-0201 was administered as 125 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 200 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 2 after determination of the maximum tolerated dose in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days
Period Title: Overall Study
STARTED	3	4	4	13
Received Study Drug	3	4	3	11
COMPLETED	3	4	3	6
NOT COMPLETED	0	0	1	7

Baseline Characteristics

Arm/Group Title	125 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	200 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	250 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	250 mg/m^2/Day RX-0201 + Everolimus (Stage 2)	Total
Arm/Group Description	RX-0201 was administered as 125 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 200 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 2 after the determination of MTD in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	Total of all reporting groups
Overall Participants	3	4	3	11	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.7 (10.79)	62.0 (12.83)	61.0 (15.87)	63.9 (6.30)	62.8 (7.87)
Sex: Female, Male (Count of Participants)
Female	0 0%	2 50%	1 33.3%	4 36.4%	7 33.3%
Male	3 100%	2 50%	2 66.7%	7 63.6%	14 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 25%	1 33.3%	1 9.1%	3 14.3%
Not Hispanic or Latino	3 100%	3 75%	2 66.7%	10 90.9%	18 85.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 25%	0 0%	1 9.1%	2 9.5%
Asian	0 0%	0 0%	0 0%	1 9.1%	1 4.8%
Native Hawaiian or Other Pacific Islander	0 0%	1 25%	0 0%	0 0%	1 4.8%
Black or African American	0 0%	1 25%	0 0%	1 9.1%	2 9.5%
White	3 100%	1 25%	2 66.7%	8 72.7%	14 66.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 33.3%	0 0%	1 4.8%
ECOG (Count of Participants)
ECOG = 0	1 33.3%	1 25%	1 33.3%	6 54.5%	9 42.9%
ECOG = 1	2 66.7%	3 75%	1 33.3%	5 45.5%	11 52.4%
ECOG = 2	0 0%	0 0%	1 33.3%	0 0%	1 4.8%

Outcome Measures

1. Primary Outcome

Title	Incidence of Dose-limiting Toxicities (DLTs) (Stage 1)
Description	Incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
Time Frame	after 1 cycle (3 weeks) of treatment with RX-0201 and everolimus

Outcome Measure Data

Analysis Population Description

DLTs were only applicable to Stage 1.

Arm/Group Title	125 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	200 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	250 mg/m^2/Day RX-0201 + Everolimus (Stage 1)
Arm/Group Description	RX-0201 was administered as 125 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 200 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days
Measure Participants	3	4	3
Count of Participants [Participants]	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Progression Free Survival (Stage 2)
Description	Median PFS. Progression determined by RECIST v1.1
Time Frame	4 months of treatment with RX-0201 and everolimus

Outcome Measure Data

Analysis Population Description

Progression Free Survival (PFS) was determined only in the Stage 2 population.

Arm/Group Title	250 mg/m^2/Day RX-0201 + Everolimus (Stage 2)
Arm/Group Description	RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 2 after the determination of MTD in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days
Measure Participants	11
Median (Standard Deviation) [days]	NA (NA)

3. Secondary Outcome

Title	Steady State Concentration (Css) of RX-0201 (Stage 1)
Description	Css of RX-0201 at the beginning and end of the 14 day continuous infusion
Time Frame	predose, 1, 2, 3, 4, 6, and 24 hours after start of Cycle 1 RX-0201 infusion, and then immediately prior to the end of Cycle 1 infusion (Day 15), 1, 2, 3, 4, 6, and 24 hours after infusion is stopped

Outcome Measure Data

Analysis Population Description

Stage 1 subjects who had sufficient PK samples for analysis

Arm/Group Title	125 mg/m^2/ Day RX-0201 Plus Everolimus (Stage 1)	200 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	250 mg/m^2/Day RX-0201 + Everolimus (Stage 1)
Arm/Group Description	RX-0201 was administered as 125 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 200 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days
Measure Participants	2	1	1
Geometric Mean (Standard Deviation) [ng/ml]	1626 (1107.2)	3283 (NA)	5147 (NA)

4. Secondary Outcome

Title	Incidence of Adverse Events, Changes in Clinical Laboratory Tests and Vital Signs Over Time (Stage 1 and Stage 2)
Description	safety of RX-0201 was evaluated through reporting using the grading system in the CTCAE version 4.03 for adverse events and laboratory abnormalities. All statistical methods for safety were descriptive in nature.
Time Frame	up to 24 weeks of treatment with RX-0201 plus everolimus and at least 30 days of safety follow up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Best Overall Response as Determined by RECIST v1.1.
Description	Best overall response as determined by RECIST v1.1. Not Evaluable included the subjects who had completed at least one treatment cycle but no overall response evaluation. Not Done included the subjects who dropped out from the study without completing any treatment cycle and overall response evaluation. The best overall response for each subject from all post-baseline time point overall responses was used. The best overall response was the best response recorded from the start of the treatment until disease progression/recurrence, or occurrence of intolerable toxicity, whatever came first.
Time Frame	Baseline and at weeks 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

All enrolled subjects with subjects analyzed according to the treatment assigned at enrollment/ randomization.

Arm/Group Title	125 mg/m^2 RX-0201 + Everolimus (Stage 1)	200 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	250 mg/m^2/Day RX-0201 + Everolimus (Stage 1)	RX-0201 Plus Everolimus (Stage 2)
Arm/Group Description	RX-0201 was administered as 125 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 200 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days	RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 2 after determination of MTD in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days
Measure Participants	3	4	4	11
Complete Response (CR)	0 0%	0 0%	0 0%	0 0%
Partial Response (PR)	0 0%	0 0%	0 0%	0 0%
Stable Disease (SD)	2 66.7%	1 25%	1 33.3%	7 63.6%
Progressive Disease (PD)	0 0%	2 50%	0 0%	1 9.1%
Not Evaluable (NE)	0 0%	0 0%	1 33.3%	0 0%
Not Done (ND)	1 33.3%	1 25%	2 66.7%	3 27.3%

6. Other Pre-specified Outcome

Title	Biomarker Concentrations in Blood
Description	Exploratory analysis of AKT pathway biomarkers, tumor apoptosis biomarkers and other biomarkers in blood or tumor samples
Time Frame	Baseline and at weeks 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	RX-0201 Concentration in the Blood (Stage 2 Only)
Description	Exploratory analysis of plasma concentrations of RX-0201 at the end of infusion
Time Frame	After 2 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events were collected from the time of first dose until the 30 days after the last dose of study drug.
Arm/Group Title	125 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		200 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		250 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		RX-0201 Plus Everolimus (Stage 2)
Arm/Group Description	RX-0201 was administered as 125 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days		RX-0201 was administered as 200 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days		RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days		RX-0201 was administered as 250 mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 2 after determination of MTD in Stage 1. 10 mg everolimus was taken daily for a cycle of 21 days
All Cause Mortality
	125 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		200 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		250 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		RX-0201 Plus Everolimus (Stage 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)		0/3 (0%)		0/11 (0%)
Serious Adverse Events
	125 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		200 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		250 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		RX-0201 Plus Everolimus (Stage 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		1/4 (25%)		2/3 (66.7%)		4/11 (36.4%)
Blood and lymphatic system disorders
Heparin-induced thrombocytopenia	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Stomatitis	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		0/11 (0%)
General disorders
Oedema peripheral	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/11 (9.1%)
Pyrexia	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/11 (9.1%)
Infections and infestations
Pseudomonas infection	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/11 (9.1%)
Injury, poisoning and procedural complications
Gastroenteritis radiation	0/3 (0%)		1/4 (25%)		0/3 (0%)		0/11 (0%)
Metabolism and nutrition disorders
Hypocalcaemia	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		0/11 (0%)
Hyponatraemia	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		0/11 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		0/11 (0%)
Renal and urinary disorders
Renal failure acute	0/3 (0%)		1/4 (25%)		0/3 (0%)		0/11 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	0/3 (0%)		1/4 (25%)		0/3 (0%)		0/11 (0%)
Pulmonary embolism	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/11 (9.1%)
Skin and subcutaneous tissue disorders
Angioedema	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	125 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		200 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		250 mg/m^2/Day RX-0201 + Everolimus (Stage 1)		RX-0201 Plus Everolimus (Stage 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		4/4 (100%)		3/3 (100%)		11/11 (100%)
Blood and lymphatic system disorders
Anaemia	1/3 (33.3%)		4/4 (100%)		2/3 (66.7%)		4/11 (36.4%)
Leukopenia	0/3 (0%)		1/4 (25%)		0/3 (0%)		1/11 (9.1%)
Neutropenia	0/3 (0%)		2/4 (50%)		0/3 (0%)		2/11 (18.2%)
Thrombocytopenia	1/3 (33.3%)		4/4 (100%)		0/3 (0%)		7/11 (63.6%)
Eye disorders
Eye swelling	0/3 (0%)		1/4 (25%)		0/3 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Abdominal pain	0/3 (0%)		1/4 (25%)		1/3 (33.3%)		0/11 (0%)
Constipation	2/3 (66.7%)		0/4 (0%)		3/3 (100%)		3/11 (27.3%)
Diarrhoea	0/3 (0%)		1/4 (25%)		2/3 (66.7%)		3/11 (27.3%)
Dry mouth	0/3 (0%)		1/4 (25%)		0/3 (0%)		2/11 (18.2%)
Faeces discoloured	0/3 (0%)		2/4 (50%)		0/3 (0%)		1/11 (9.1%)
Nausea	0/3 (0%)		2/4 (50%)		3/3 (100%)		7/11 (63.6%)
Stomatitis	2/3 (66.7%)		1/4 (25%)		3/3 (100%)		5/11 (45.5%)
Vomiting	0/3 (0%)		0/4 (0%)		2/3 (66.7%)		4/11 (36.4%)
General disorders
Asthenia	0/3 (0%)		1/4 (25%)		1/3 (33.3%)		0/11 (0%)
Chills	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/11 (18.2%)
Face oedema	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		1/11 (9.1%)
Fatigue	2/3 (66.7%)		1/4 (25%)		1/3 (33.3%)		7/11 (63.6%)
Influenza like illness	0/3 (0%)		1/4 (25%)		0/3 (0%)		1/11 (9.1%)
Oedema peripheral	1/3 (33.3%)		0/4 (0%)		1/3 (33.3%)		4/11 (36.4%)
Pain	0/3 (0%)		1/4 (25%)		0/3 (0%)		2/11 (18.2%)
Pyrexia	0/3 (0%)		1/4 (25%)		0/3 (0%)		3/11 (27.3%)
Infections and infestations
Sinusitis	0/3 (0%)		1/4 (25%)		1/3 (33.3%)		0/11 (0%)
Injury, poisoning and procedural complications
Contusion	1/3 (33.3%)		2/4 (50%)		0/3 (0%)		2/11 (18.2%)
Investigations
Blood creatinine increased	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		1/11 (9.1%)
Lipase increased	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/11 (18.2%)
Weight decreased	1/3 (33.3%)		0/4 (0%)		2/3 (66.7%)		3/11 (27.3%)
Metabolism and nutrition disorders
Decreased appetite	1/3 (33.3%)		0/4 (0%)		3/3 (100%)		6/11 (54.5%)
Hyperglycaemia	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/11 (18.2%)
Hyperkalaemia	0/3 (0%)		0/4 (0%)		2/3 (66.7%)		0/11 (0%)
Hypokalaemia	0/3 (0%)		0/4 (0%)		0/3 (0%)		3/11 (27.3%)
Hyponatraemia	1/3 (33.3%)		1/4 (25%)		2/3 (66.7%)		1/11 (9.1%)
Hypophosphotaemia	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		2/11 (18.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/3 (0%)		1/4 (25%)		0/3 (0%)		2/11 (18.2%)
Back pain	0/3 (0%)		1/4 (25%)		1/3 (33.3%)		3/11 (27.3%)
Bone pain	0/3 (0%)		1/4 (25%)		1/3 (33.3%)		0/11 (0%)
Musculoskeletal chest pain	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		2/11 (18.2%)
Musculoskeletal stiffness	1/3 (33.3%)		0/4 (0%)		1/3 (33.3%)		0/11 (0%)
Myalgia	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		1/11 (9.1%)
Nervous system disorders
Dizziness	0/3 (0%)		2/4 (50%)		0/3 (0%)		4/11 (36.4%)
Dysgeusia	0/3 (0%)		1/4 (25%)		0/3 (0%)		4/11 (36.4%)
Headache	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		2/11 (18.2%)
Psychiatric disorders
Anxiety	0/3 (0%)		1/4 (25%)		1/3 (33.3%)		1/11 (9.1%)
Insomnia	1/3 (33.3%)		0/4 (0%)		1/3 (33.3%)		4/11 (36.4%)
Renal and urinary disorders
Haematuria	2/3 (66.7%)		0/4 (0%)		0/3 (0%)		1/11 (9.1%)
Nocturia	1/3 (33.3%)		1/4 (25%)		0/3 (0%)		1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		2/11 (18.2%)
Epistaxis	1/3 (33.3%)		1/4 (25%)		1/3 (33.3%)		7/11 (63.6%)
Haemoptysis	0/3 (0%)		0/4 (0%)		0/3 (0%)		3/11 (27.3%)
Hiccups	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		1/11 (9.1%)
Nasal congestion	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		2/11 (18.2%)
Oropharyngeal pain	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		1/11 (9.1%)
Wheezing	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		1/11 (9.1%)
Skin and subcutaneous tissue disorders
Dermatitis bullous	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/11 (18.2%)
Night sweats	0/3 (0%)		1/4 (25%)		1/3 (33.3%)		1/11 (9.1%)
Pruritus	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		6/11 (54.5%)
Rash maculo-papular	0/3 (0%)		0/4 (0%)		0/3 (0%)		4/11 (36.4%)
Vascular disorders
Hypotension	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/11 (18.2%)

Limitations/Caveats

Early termination lead to small numbers of subjects analyzed. Missing samples and technical problems with the bioanalysis resulted in uninterpretable PK data.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.