RNActive®-Derived Therapeutic Vaccine

• Sponsor: University of Florida (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00906243
• Collaborator: CureVac AG (Industry)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 19
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a Phase I/IIa open, uncontrolled, prospective study, to be conducted in an out-patient setting. The present study is one of two clinical trials of the RNActive®-derived vaccine CV9103 being conducted concurrently in the US and Europe, which represent the first clinical trials conducted for this novel vaccine.

The Phase I part of the study consists of a staggered inclusion of subjects in two cohorts of 3, to confirm the safety of the intended dose (320 µg RNA per antigen), with a lower dose to be considered in case of dose-limiting toxicity (DLT) being reported in greater than or equal to 2 out of 3-6 subjects; in this way, the recommended dose (RD) for the Phase IIa part of the study will be established. In the Phase IIa part of the study, additional subjects will be included at the RD, to confirm the safety and explore the activity of that dose.

Condition or Disease	Intervention/Treatment	Phase
Hormone Refractory Prostate Cancer	Biological: CV9103	Phase 1/Phase 2

Detailed Description

Medical Need:

At present, no curative therapy is available for subjects with advanced or metastatic prostate cancer. Approximately 1 of every 3 men present with advanced or metastatic disease; therefore, current standard therapies are ineffective and new therapeutic approaches are warranted. There is ample evidence that active immunotherapy against cancer is safe and capable of stimulating potentially therapeutic immune responses in the cancer patient. Moreover, several Phase II immunotherapy trials have suggested clinical benefit by reducing the tumor mass or prolonging time to progression in subjects with advanced prostate cancer.

Potential Benefits:

CV9103 is an mRNA-based vaccine for the treatment of human prostate cancer that is based on CureVac's RNActive® technology. CV9103 encodes for 4 prostate specific antigens. Because these antigens are present in prostate cancer cells, they are appropriate targets for intervention. These antigens have been shown to correlate frequently with the progression of prostate cancer, and are known to be immunogenic in humans, where they induce antigen specific T-cell or B cell expansion.

As an RNA-based vaccine, CV9103 features several advantages over other approaches: it is highly specific, there is no restriction to the patient's MHC genotype, and it does not need to cross the nuclear membrane to be active. Finally, in the absence of reverse transcriptase, RNA can not be integrated into the genome.

CV9103 will be administered in 5 doses.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/IIa Study of RNActive®-Derived Therapeutic Vaccine in Advanced or Metastatic Hormone Refractory Prostate Cancer
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CV9103 CV9103 will be applied intradermally on three (3) or five (5) time points. Treatment with CV9103 is administered over a period of either seven (7) or twenty-three (23) weeks.	Biological: CV9103; CV9103 encodes for 4 prostate specific antigens.

Outcome Measures

Primary Outcome Measures

1. Phase I: Assessment of Safety and Tolerability of the Trial Regimen [At Nine Weeks with Follow Up at One Year]

   Dose Limiting Toxicity (DLT) is defined as the following treatment-related adverse events or laboratory abnormalities, graded according to NCI-CTCAE version 3.0: All Categories equal or greater than grade 3 Allergy/autoimmunity equal or greater than grade 2 Dosing delay greater than 48 hours due to toxicity All adverse events will be graded and documented according to Common Terminology Criteria for Adverse Events version 3.0.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with documented history of hormone refractory prostate cancer as evidenced by three consecutive increases in serum PSA despite continued androgen ablative therapy. Serum testosterone levels must be less than 50 ng/dl

• Signed informed consent in accordance with Good Clinical Practice (GCP) and local regulatory requirements prior to trial participation

• Age greater than or equal to 18 yrs (Phase I and IIa) and less than or equal to 75 yrs (Phase IIa only)

• ECOG (Eastern Cooperative Oncology Group) Grade of 0 or 1

• Adequate Hematologic Function with:

• WBC ≥ 3000 mm3

• hemoglobin ≥ 10mg/dl

• platelets ≥ 100,000/mm3

• Adequate Renal and Hepatic Function with:

• serum creatinine ≤ 1.5 x Upper Limit of Normal

• bilirubin < 2.0 mg/dl

• Adequate Coagulation Parameters with:

• Prothrombin INR < 1.5

• Partial Thromboplastin Time < 1.5 x Institutional Upper Limit of Normal

• Subjects will be advised to use barrier contraception while enrolled in the study and for one month after the last immunization.

• Life Expectancy > 6 month

Exclusion Criteria:

• Subjects who have received radiation therapy within 8 weeks of pretreatment evaluation. (There must be at least 12 weeks if prior therapy included 89-Strontium between any prior therapy and study entry.)

• Subjects who have received chemotherapy, radiation therapy or biologic regimens within 8 weeks of pretreatment evaluation.

• Subjects treated with any investigational agent within the past 30 days are excluded.

• Subjects who have received active immunotherapy, such as Antigen Loaded Dendritic Cells, are excluded (Phase I only). In Phase IIa, Subjects who have received an active immunotherapy based on any of the antigens used in this study either as DNA, RNA or a protein/peptide-based vaccines are excluded. Subjects who have received any other active immunotherapy, such as Antigen Loaded Dendritic Cells, within 6 months prior to study entry are also excluded.

• Subjects who have not recovered from radiation, chemotherapy, or immunotherapy toxicities.

• Subjects with either previously irradiated or new CNS (central nervous system) metastases. (Pre-enrollment head CT is not required.)

• Subjects with a history of autoimmune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis.

• Subjects with serious intercurrent chronic or acute illness such as pulmonary [asthma or chronic obstructive pulmonary disease (COPD)] or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment.

• Medical or psychological impediment to probable compliance with the protocol.

• Concurrent second malignancy other than non-melanoma skin cancer, or controlled superficial bladder cancer. In the event of prior malignancies treated surgically, the subject must be considered NED (no evidence of disease) for a minimum of 3 years prior to enrollment.

• Subjects on steroid therapy (or other immunosuppressive agents such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression. Subjects must have had 8 weeks of discontinuation of any steroid therapy prior to enrollment.

• Presence of an active acute or chronic infection, including symptomatic urinary tract infection, HIV (as determined by ELISA and confirmed by Western Blot) or viral hepatitis (as determined by HBsAg and Hepatitis C serology).

• Subjects with penicillin allergies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida, College of Medicine	Gainesville	Florida	United States	32610

Sponsors and Collaborators

• University of Florida
• CureVac AG

Investigators

• Principal Investigator: Johannes Vieweg, MD FACS, Univeristy of Florida, College of Medicine

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Department Website

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT00906243
• Other Study ID Numbers: CV-9103-002
• First Posted: May 21, 2009
• Last Update Posted: Apr 4, 2012
• Last Verified: Feb 1, 2012

• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	A total of 6 subjects entered Phase 1 of the study between June 2009 and December 2009.

Arm/Group Title	CV9103
Arm/Group Description	CV9103 will be applied intradermally on three (3) or five (5) time points. Treatment with CV9103 is administered over a period of either seven (7) or twenty-three (23) weeks.
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	CV9103
Arm/Group Description	CV9103 will be applied intradermally on three (3) or five (5) time points. Treatment with CV9103 is administered over a period of either seven (7) or twenty-three (23) weeks.
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 33.3%
>=65 years	4 66.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.1 (9.58)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	6 100%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Phase I: Assessment of Safety and Tolerability of the Trial Regimen
Description	Dose Limiting Toxicity (DLT) is defined as the following treatment-related adverse events or laboratory abnormalities, graded according to NCI-CTCAE version 3.0: All Categories equal or greater than grade 3 Allergy/autoimmunity equal or greater than grade 2 Dosing delay greater than 48 hours due to toxicity All adverse events will be graded and documented according to Common Terminology Criteria for Adverse Events version 3.0.
Time Frame	At Nine Weeks with Follow Up at One Year

Outcome Measure Data

Analysis Population Description

Phase 1 consisted of cohort 1 with 3 subjects and cohort 2 with three subjects.

Arm/Group Title	CV9103
Arm/Group Description	CV9103 will be applied intradermally on three (3) or five (5) time points. Treatment with CV9103 is administered over a period of either seven (7) or twenty-three (23) weeks.
Measure Participants	6
Number [events]	6

Adverse Events

Arm/Group Title	CV9103
Arm/Group Description	CV9103 will be applied intradermally on three (3) or five (5) time points. Treatment with CV9103 is administered over a period of either seven (7) or twenty-three (23) weeks.
All Cause Mortality
	CV9103
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	CV9103
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	CV9103
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Endocrine disorders
Hypothyroidism	1/6 (16.7%)	1
Gastrointestinal disorders
Constipation	1/6 (16.7%)	1
General disorders
Erythema	6/6 (100%)	6
Induration	6/6 (100%)	6
Fatigue	2/6 (33.3%)	2
Influenza Like Illness	1/6 (16.7%)	1
Oedema Peripheral	1/6 (16.7%)	1
Infections and infestations
Oral Fungal Infection	1/6 (16.7%)	1
Rhinitis	1/6 (16.7%)	1
Investigations
Weight Decreased	1/6 (16.7%)	1
Metabolism and nutrition disorders
Anorexia	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
Myalgia	2/6 (33.3%)	2
Arthraligia	1/6 (16.7%)	1
Back Pain	1/6 (16.7%)	1
Nervous system disorders
Headache	2/6 (33.3%)	2
Peripheral motorneuropathy	1/6 (16.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/6 (16.7%)	1
Ordpharyngeal pain	1/6 (16.7%)	1
Skin and subcutaneous tissue disorders
Pruitus	1/6 (16.7%)	1
Rash	1/6 (16.7%)	1
Surgical and medical procedures
Skin Neopasm Excision	1/6 (16.7%)	1

Limitations/Caveats

This study was terminated early by decision of the Sponsor after 6 subjects had been enrolled in the Phase I part of the study. No efficacy evaluations were planned during the Phase I part of the study.

More Information

Certain Agreements

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

This was a Phase 1 and Phase 2 study. The study was terminated after completion of Phase 1 under terms of a settlement agreement that restricts disclosure to limited Phase 1 results only.