Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Adenocarcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Papillary Renal Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Immunomodulating Agents

Sunitinib

Interferons

Trovax

Placebo

subcutaneous low dose IL-2, interferon-α or sunitinib

Standard of care therapy

The purpose of this study is to investigate whether TroVax, when added to first line standard of care therapy, improves survival for patients with locally advanced or metastatic clear cell renal adenocarcinoma.

This is an international, randomised, double blind, placebo controlled, parallel group study to investigate whether a minimum of three doses of TroVax® added to first-line standard of care therapy, prolongs the survival of patients with locally advanced or metastatic renal clear cell adenocarcinoma.

The primary endpoint is survival. The study is designed to be pragmatic, limiting additional study related investigations to a minimum. Protocol mandated scans and X-rays are limited to two time points (baseline and week 26) to permit comparison of the percentage of patients with progressive disease at 6 months as a secondary efficacy endpoint. Six months was selected based on review of published literature indicating that progressive disease was commonly observed by 26 weeks in patients with renal cancer. Endpoints such as tumour response by RECIST are considered of secondary importance to survival and will be determined by radiological examinations ordered at the discretion of the investigator based on the clinical status of the patient and will be based the interpretation of the patient's care-team (investigator and local radiologist).

After signing the study informed consent form and meeting the baseline enrolment criteria patients will be assigned by the investigator (their physician) to one of the following defined first-line standard of care regimens based on what is best for the patient and consistent with local practice:

1. subcutaneous low dose IL-2
2. interferon-α (excluding pegylated IFNα)
3. sunitinib

TroVax® is administered at a dose of 1E9TCID50/ml in 1ml by injection into the deltoid muscle of the upper arm at regular intervals up to 8 weeks apart up to a maximum of 13 doses.

TroVax Renal Immunotherapy Survival Trial

Randomised,Double-blind,Placebo-controlled,Parallel Group Study TroVax, Added to First-line Standard of Care, Prolongs Survival of Patients With Locally Advanced or Metastatic Clear Cell Renal Adenocarcinoma.

Sanofi

Oxford BioMedica

Vaccines

TroVax given as first or second line treatment in conjuntion with low dose IL-2.

TroVax

IL-2 250,000 U/kg S/C for cycle 1 and day 1 of subsequent cycles, 125,000U/kg S/C for days 2-5 of cycles 2-6

IL-2

Robert J Amato, MD

The purpose of this study is to assess the safety and tolerability of TroVax® investigational vaccine injections when given as first or second line treatment in conjunction with subcutaneous low dose IL-2 to patients with locally advanced or metastatic clear cell or papillary cell renal carcinoma.

TroVax® is the experimental product in this trial and its value as a medicine has not yet been proven. Interleukin-2 (IL-2) is a standard treatment for cancer, which means that it can be received even if one chooses not to participate in this study. TroVax® is being studied as a possible treatment for patients with cancer of the kidney.

TroVax® belongs to a class of medicines called vaccines. A vaccine helps the body's immune system to recognize and kill foreign invading organisms effectively. It is believed that one of the reasons why cancer can spread through the body is that the immune system cannot recognize cancer cells as being different from normal tissues and therefore cannot kill the cancer cells. A vaccine that alerts the immune system to the presence of cancer cells in the body could lead to the immune system being able to target and kill those cancer cells effectively. This trial is of a completely new way of trying to treat cancer in the future by the use of vaccination injections. TroVax® consists of a virus that has been changed so that it is no longer infectious and carries a gene for a protein called 5T4. This protein is carried by many kidney cancer cells. When the virus is injected, it makes the protein, and the body's immune system is then able to recognize this protein and kill the cells that have it (i.e. the cancer cells).

The purpose of this study is to assess the safety and tolerability of TroVax® injections and to understand whether TroVax® could make such an immune response happen in patients with renal cell cancer while receiving interleukin-2 (IL-2). This study will also observe and monitor any side effects experienced in patients who receive TroVax® while being treated with IL-2.

Objectives

Primary:

* To assess the safety and tolerability of TroVax® injections when given as first or second line treatment in conjunction with subcutaneous low dose IL-2 to patients with locally advanced or metastatic clear cell or papillary cell renal carcinoma.
* To assess the immune responses induced by treatment with TroVax® and subcutaneous low dose IL-2.

Secondary:

* To assess tumour response rates, time to progression, survival and progression free survival at 6, 12 and 24 months after commencement of treatment with subcutaneous low dose IL-2.
* To assess the ability of the reintroduction of low dose subcutaneous IL-2 to induce further disease responses or stabilisation in patients being treated with TroVax® alone.

Study design:

This will be an open label evaluation in patients with clear cell or papillary cell renal carcinoma requiring immunotherapy for locally advanced or metastatic disease. A single dose level of TroVax® in combination with a clinically accepted regimen of subcutaneous low dose IL-2 will be tested in 25 evaluable patients and their immunological responses to TroVax® (antibody and cellular) will be assessed. If immunological activity is observed after two cycles of TroVax®/IL-2 in 70% or more of these patients, further randomised trials will be undertaken to determine the clinical efficacy of TroVax® in this group of patients.

The dosage schedule of subcutaneous low dose IL-2 will be an initial dose schedule of 250,000 U/kg/dose for 5 days in week 1 followed by 125,000 U/kg/dose for 5 days in each of weeks 2 though 6 inclusive. There will then be a two-week recovery period before the next cycle commences. The dosage regimen of TroVax® will be injections given prior to the first cycle on two occasions (weeks -2 and 1), and one injection given at the beginning of week 4 of the first cycle. In subsequent cycles, booster injections of TroVax® will be given at week 1 only, prior to commencement of subcutaneous IL-2 therapy. After the first and second cycles of combined treatment, patients will be evaluated by CT scan for their response to treatment. If their disease has progressed after the second cycle, they will be withdrawn from the trial if they require alternative therapy (deterioration of one level of the Karnofsky score or appearance of disease in a new site). If they are experiencing progressive disease that does not require alternative therapy or stable disease or better, they will be treated with cycles of TroVax®/IL-2 as described above for up to a further four cycles. The tumour status will be evaluated by CT scan after every cycle.

All patients will be monitored for up to 6 cycles (48 weeks) to assess tolerability, induction of humoural and cellular immunity to 5T4 cell surface antigen, immune response to the vector, tumour response rates, survival, time to progression and progression free survival. Patients who are intolerant of further treatments with subcutaneous IL-2 during this part of the study will be withdrawn from the study.

Patients who are still stable or experiencing a tumour response at 48 weeks will be offered further boosts with TroVax® without IL-2 every three months at weeks 52, 64, 76, 88 and 100. During this period, if disease progression recurs, two further cycles with subcutaneous IL-2 as described above may be given in combination with TroVax® as described above with the objective of inducing further disease response or stabilisation.

Following termination of all patients' participation in the trial (including those with progressive disease after two cycles of TroVax®/IL-2), contact will be kept by the Investigators with their families in order to determine the date of death.

A total of 25 patients will be enrolled.

Withdrawal criteria from the trial:

1. Non-compliance with the protocol.
2. Patient withdraws consent.
3. Progressive disease with new sites of disease demonstrated on CT scan and/or requiring other cancer treatment (deterioration in Karnofsky performance score of 10% or more).
4. Death.
5. Serious IL-2 related adverse events or lack of tolerance to further treatment with IL-2
6. Serious TroVax® related adverse events (DLT).

   Treatment plan and methods:

   Patients complying with the entry criteria will be invited to enter the study. After giving fully informed consent, patients will be subjected to a physical examination to document general fitness to proceed with the trial. Vital signs will be recorded. Performance status (Karnofsky) will be documented. At that time, metastases will be documented using chest, abdominal and pelvic CT scans and an MRI scan of the brain will be obtained. Blood samples will also be obtained for clinical pathology (10 mL; safety testing). A urine sample will be tested for protein and blood (safety testing). A 12 lead ECG and echocardiogram will be obtained. This screen should not occur more than two weeks before treatment with TroVax® begins. If available, tumour tissue from earlier biopsies will be obtained and tested for the presence of tumour antigens, e.g. 5T4. CT scans must be compared with scans obtained within the previous three months in order to determine that the disease is progressing.

   Week -2, day 1:

   Obtain blood sample for HLA testing and immunological evaluation, (antibody and T-cell responses to the vector and the 5T4 surface antigen; 100 mL).

   Safety testing (blood, 10 mL and urine) TroVax® injection i.m. 1 mL

   Cycle 1, Week 1 day 1:

   Karnofsky score Vital signs TroVax® injection i.m. 1 mL (time 0) Vital signs (1 hour) / Vital signs (3 hours) IL-2 subcutaneous injection (250,000 U/kg/dose) safety testing

   Cycle 1, Week 1, days 2-5:

   IL-2 subcutaneous injection (250,000 U/kg/dose)

   Cycle 1, Week 2, day 1:

   Obtain samples for immunological evaluation (100 mL blood) and safety testing (blood 10 mL and urine) IL-2 subcutaneous injection (125,000 U/kg/dose).

   Week 2, days 2-5:

   IL-2 injection subcutaneous (125,000 U/kg/dose).

   Week 3, days 1-5:

   Safety testing (blood and urine; day 1 only) IL-2 subcutaneous injection (125,000 U/kg/dose).

   Week 4, day 1:

   Safety testing Vital signs TroVax® injection i.m. 1 mL (time 0) Vital signs (1 hour) / Vital signs (3 hours) IL-2 subcutaneous injection (125,000 U/kg/dose).

   Week 4, days 2-5:

   IL-2 subcutaneous injection (125,000 U/kg/dose).

   Week 5, days 1-5:

   Obtain sample for immunological evaluation (blood) and safety testing (blood 10 mL and urine; day 1 only) IL-2 subcutaneous injection (125,000 U/kg/dose).

   Week 6, days 1-5:

   Obtain sample for safety testing (blood 10 mL and urine; day 1 only) IL-2 subcutaneous injection (125,000 U/kg/dose).

   Week 8 day 1:

   CT scan for information. Physician examination. Safety blood (10 mL) and urine

   Cycles 2-6 week 1, day 1:

   Obtain sample for safety testing (blood 100 mL and urine) Vital signs Karnofsky score TroVax® injection i.m. 1 mL (time 0) Vital signs (1 hour) / Vital signs (3 hours) IL-2 subcutaneous injection (250,000 U/kg/dose)

   Cycle 2-6, week 1, days 2-5:

   IL-2 subcutaneous injection (250,000 U/kg/dose)

   Cycles 2-6, Week 2, day 1:

   Obtain sample for immunological evaluation (blood) and safety testing (blood and urine).

   IL-2 subcutaneous injection (125,000 U/kg/dose).

   Cycles 2-6, Week 2, days 2-5:

   IL-2 subcutaneous injection (125,000 U/kg/dose).

   Cycles 2-6, Weeks 3-6, days 1-5:

   Safety testing (blood 10 mL and urine day 1 only) IL-2 subcutaneous injection (125,000 U/kg/dose)

   Cycles 2-6, Week 8, day 1:

   Obtain blood for safety testing (blood and urine) CT scan. Physician examination.

   At the end of cycle 2 to 6 inclusive, if disease has progressed and requires other treatment (deterioration in Karnofsky performance score by 10% or more, disease appears in a new site), withdraw patient from trial. Also withdraw patient if intolerant of subcutaneous low dose IL-2 at the lowest permissible dose or if the patient experiences DLT. Patients withdrawing before they receive the first four doses of TroVax® and give blood for immunology testing in cycle 2, week 2 will be replaced.

   If disease is stable, responding or progressing (but Karnofsky score unchanged, no new disease sites) and patient is tolerant of treatment, continue with further therapy.

   After six cycles of combined study drugs (48 weeks), assess with CT scan at week 48 day 1:

   If disease has progressed and requires alternative treatment (deterioration in Karnofsky performance score by 10% or more or disease appears in a new site), withdraw patient from trial.

   If disease is stable or responding or progressing (but Karnofsky score stable and no new disease sites) and patient is tolerant of treatment, continue with further therapy. This therapy will be TroVax® injection every three months, on weeks 52, 64, 76, 88, 100. Perform physician examination on each occasion and assess Karnofsky score prior to injection. Obtain samples for safety testing (blood 10 mL and urine) and immunological evaluation (10 mL sample only for antibody testing) prior to each injection. A further 10 mL sample for immunological evaluation will be obtained one week after each TroVax® injection. CT scans will be obtained at weeks 63, 75, 87, 99. At each CT scan, assess:

   If disease has progressed, recommence subcutaneous low dose IL-2 treatment (6 weeks on, two weeks off IL-2) at week 64, 76, 88 as appropriate and give a further 2 cycles of subcutaneous low dose IL-2.

   If IL-2 restarted at week 64 (76, 88), schedule is:

   Week 64 (or 76, 88), day 1:

   Safety testing (blood 10 mL and urine) TroVax® injection i.m. 1 mL Karnofsky score IL-2 subcutaneous injection (250,000 U/kg/dose) Physical examination

   Week 64 (or 76, 88), days 2-5:

   IL-2 subcutaneous injection (250,000 U/kg/dose)

   Week 65 (or 77, 89), days 1-5:

   Safety testing (blood 10 mL and urine, day 1 only). Immunological evaluation, 10 mL sample only (day 1 only) IL-2 subcutaneous injection (125,000 U/kg/dose).

   Weeks 66-69 (or 78-81, or 90-93), days 1-5:

   Safety testing (blood 10 mL and urine, day 1 only). IL-2 subcutaneous injection (125,000 U/kg/dose).

   Week 71 (or 83 or 95) day 1:

   Physician examination. CT scan.

   Second Cycle:

   Week 72 (or 84, 96), day 1:

   Safety testing (blood 10 mL and urine) TroVax® injection i.m. 1 mL Karnofsky score IL-2 injection (250,000 U/kg/dose)

   Week 72 (or 84, 96), days 2-5:

   IL-2 injection (250,000 U/kg/dose)

   Week 73 (or 85, 97), days 1-5:

   Safety testing (blood 10 mL and urine, day 1 only). Immunological evaluation, 10 mL sample only (day 1 only) IL-2 subcutaneous injection (125,000 U/kg/dose).

   Weeks 74-77 (or 86-89, or 98-101), days 1-5:

   Safety testing (blood and urine, day 1 only). IL-2 subcutaneous injection (125,000 U/kg/dose).

   Week 79 (or 91 or 103) day 1:

   Physician examination. CT scan.

   After the second cycle of IL-2, if disease has progressed and requires other treatment (deterioration in Karnofsky score by 10% or more, disease appears in a new site), withdraw patient from trial.

   If the treatment cycles with IL-2 end before week 104 and the patient is responding, stable or progressing but not in need of alternative therapies (Karnofsky stable, no new disease sites), recommence TroVax® on the original schedule (see Flow Chart). If disease is progressing and requires further therapy (deterioration in Karnofsky score by 10% or more, disease appears in a new site), withdraw patient from trial.

   Four weeks after the final treatment, all patients will, if possible, attend for a final follow up visit. The following will be obtained:

   Physical examination. Karnofsky score Safety testing (blood 10 mL and urine).

   All study visits must occur within +/- 3 days of the day stipulated in the protocol.

   If patients withdraw at any time during the trial, a final follow up visit, if possible, will be obtained four weeks after withdrawal.

   Concomitant medication and adverse events will be recorded at each visit.

Safety and Biological Activity of TroVax® Vaccine Given With IL-2 in Renal Cell Carcinoma

Safety, Immunology, and Biological Activity Evaluation of TroVax® in Treatment of Patients With Locally Advanced or Metastatic Renal Carcinoma

To assess the safety and tolerability of TroVax injections when given as first or second line treatment in conjunction with subcutaneous low dose IL-2 to patients with locally advanced or metastatic clear cell or papillary cell renal carcinoma.

To assess the immune responses induced by treatment with TroVax and subcutaneous IL-2

To assess tumour response rates, time to progression, surgival and progression free surgival at 6, 12 and 24 months after commencement of treatment with subcutaneous low dose IL-2.

To assess the ability of the reintroduction of low dose subcutaneous IL-2 to induce further disease responses or stabilisation in patients being treated with TroVax alone.

The Methodist Hospital Research Institute

ORION Clinical Services

Analgesics

Interleukin-2

Analgesics, Non-Narcotic

TroVax: Intramuscular into the deltoid muscle of the upper arm, 10x dose (6.83 x 108 pfu/ml). IL 2: High dose IL 2, 600,000 IU/kg intravenously every 8 hours up to a maximum of 15 injections.

Howard L Kaufman, MD

The purpose of this study is to test the safety of an investigational vaccine called TroVax when given in conjunction with Interleukin-2 (IL-2) treatment. TroVax is the experimental product in this trial and its value as a medicine has not yet been proven. Interleukin-2 (IL-2) is standard treatment for your cancer, which means that you could receive it even if you choose not to participate in this study. TroVax is being studied as a possible treatment for patients with cancer of the kidney.

TroVax belongs to a class of medicines called a vaccine. A vaccine helps the body's immune system to recognize and kill foreign invading organisms effectively. It is believed that one of the reasons why cancer can spread through the body is that the immune system cannot recognize them as being different from normal tissues and therefore cannot kill the cancer cells. A vaccine that alerts the immune system to the presence of cancer cells in the body could lead to the immune system being able to target and kill those cancer cells effectively. This trial is of a completely new way of trying to treat cancer in the future by the use of vaccination injections. TroVax consists of a virus that has been changed so that it is no longer infectious and carries a gene for a protein called 5T4. This protein is carried by many kidney cancer calls. When the virus is injected, it makes the protein, and the body's immune system is then able to recognize this protein and kill the cells that have it (i.e. the cancer cells).

The purpose of this study is to assess the safety and tolerability of TroVax injections and to understand whether TroVax could make such an immune response happen in patients with renal cell cancer while receiving Interleukin-2 (IL-2). This study will also observe and monitor any side effects experienced in patients who receive TroVax while being treated with IL-2.

Objectives

Primary

* To assess the safety and tolerability of TroVax injections when given as a therapeutic vaccine to patients with metastatic renal cell cancer
* To assess the immune responses induced by treatment with TroVax

Secondary

* To assess the impact of treatment with TroVax on tumour response rates, time to disease progression and two year survival.

Study design This will be an open label evaluation of the combination of TroVax with IL-2. The dosage regimen will be injections of TroVax given at three weekly intervals commencing before treatment with IL-2 (one treatment) and then in conjunction with IL-2 for up to four treatments. Following completion of treatment with IL-2, booster injections of TroVax will be given at three monthly intervals for a further three injections to patients whose disease responds or stabilises after treatment with IL-2 and TroVax.

The first dose of TroVax will be given alone to allow an initial safety assessment. The second dose will be given with the standard institutional regimen of high dose IL-2. IL-2 will be given for 5 consecutive days every three weeks for two or more (typically four) cycles provided that the patients are responding to treatment (i.e. tumour response or stabilisation). The first dose of IL-2 will be given starting on the same day as the second TroVax injection. If the patient does not tolerate treatment with IL-2, dosing with TroVax will continue on a three weekly cycle until a total of 5 injections has been given (week 12). Following this, TroVax boosters will be given every at six, nine and 12 months providing that the disease remains stable or responding. The total treatment period may last for up to 12 months with a further follow up period of up to 12 months (total study period 24 months).

All patients will be followed up to assess tolerability, induction of humoural and cellular immunity to 5T4 cell surface antigen and immune response to the vector. The tumour will be restaged after every two cycles of IL-2 treatment by CT scans, in accordance with current institutional and clinical guidelines. Once treatment with IL-2 has stopped, boosting and restaging will occur every 3 months for a total treatment period of up to one year. Once this treatment has stopped, patients will be followed for a further twelve months, with CT scans every 3 months (standard of care). If at the end of that period, the patient still has stable or responding disease, that patient will be followed at three monthly intervals until disease progression occurs.

If the patients' disease progresses at any stage or serious or severe adverse drug reactions relating to TroVax occur, treatment with TroVax will cease but patients should be kept on study and followed three monthly until they have been on study for 24 months. Other treatments for the cancer will be recorded in the CRF.

A total of 25 patients will be enrolled.

Study population Inclusion criteria

1. Metastatic renal clear cell adenocarcinoma, histologically proven by biopsy of the primary tumour and/or a metastasis. If a fresh specimen is obtained for diagnostic purposes, it may be frozen and stained for 5T4. Prior nephrectomy is not required.
2. Requiring treatment with IL-2 and able to tolerate a high dose schedule per institutional standards.
3. Aged 18 years or more.
4. Performance status (ECOG) 0 or 1.
5. Expected survival longer than three months.
6. No clinically active autoimmune disease.
7. Total white cell count ≥ 3 x 109/l.
8. Platelet count ≥ 90,000/mm3.
9. Serum creatinine 1.6 mg/dl or less.
10. Total bilirubin 1.6 mg/dl or less.
11. Serum AST/ALT ≥ three times the upper limit of normal or 5 times upper limit of normal if liver metastases are present.
12. Able to give written informed consent and to comply with the protocol.
13. Women must be either post menopausal, rendered surgically sterile or practising a reliable form of contraception (hormonal, intrauterine device or barrier). Men must practise an effective form of birth control, such as barrier protection.
14. Normal cardiac stress test if the patients are older than 50 years of age or have symptoms of cardiac disease.
15. Normal pulmonary function tests if the patient is a smoker or is known to have primary lung disease.

Exclusion criteria

1. Pregnancy, lactation or lack of effective contraception in fertile men and women of childbearing potential.
2. Intercurrent serious infections within the 28 days prior to entry to the trial.
3. Known to be HIV positive because HIV infection can lead to serious adverse events with vaccination and/or high-dose IL-2.
4. Life threatening illness unrelated to cancer.
5. Cerebral metastases.
6. History of allergic response to previous vaccinia vaccinations.
7. Participation in any other clinical trial within the previous 30 days .
8. Previous malignancies within the last two years other than successfully treated squamous carcinoma of the skin or in situ carcinoma of the cervix treated with cone biopsy.
9. Previous history of major psychiatric disorder requiring hospitalisation or any current psychiatric disorder that would impede the patient's ability to provide informed consent or to comply with the protocol.
10. Corticosteroids unless used as an antiemetic.
11. Family contact with active eczema, exfoliative skin disorder, pregnancy or other cause of immunocompromise.

Withdrawal criteria

1. Non-compliance with the protocol.
2. Patient request.
3. Physician decision.
4. Concurrent involvement in a clinical trial of any other drug. Treatment plan and methods This will be an open label evaluation of the combination of TroVax with IL-2. The dosage regimen will be three injections of TroVax given every three weeks. The first vaccine will be given alone. The second and third vaccine will be given at weeks 3 and 6 with IL-2 commencing immediately after vaccination. If there is no evidence of disease progression on the week 9 CT scans (chest, abdomen, pelvis), an additional two cycles of TroVax and IL-2 will be given at weeks 9 and 12. Following completion of treatment with IL-2, booster injections of TroVax will be given at three monthly intervals for a further three injections, provided patients have stable or responding disease.

Patients complying with the entry criteria will be invited to enter the study. After giving fully informed consent, patients will be subjected to a medical history and physical examination to document general fitness to proceed with the trial. Previous exposure to small pox vaccine will be noted. The diagnosis should be confirmed histologically from the patient's records. If possible, a retained sample will be obtained to stain for 5T4. If a fresh sample is taken, it may be cryopreserved and also examined for 5T4. At that time, metastases will be documented using relevant CT scans (chest, abdomen, pelvic). An MRI scan of the brain will be obtained. A cardiac stress test and pulmonary function tests will be obtained in appropriate patients.

Blood will also be drawn for haematology and clinical chemistry, full blood count with differential white cell and platelet counts, urea and electrolytes, liver function tests (total bilirubin, AST, ALT, GGT, alkaline phosphatase), serum proteins, calcium, phosphate, glucose and creatinine), pituitary hormone screen (ACTH, TSH, LH, FSH;), antinuclear and anti-skeletal muscle antibodies and immunological testing (antibodies to 5T4 and vector, cellular responses to 5T4; 100 ml). In potentially fertile women, a pregnancy test will be obtained. A urine sample will be obtained for urinalysis for protein and blood. This screen should not occur more than two weeks before the immunisation schedule begins.

At week 0, the patients will be immunised with a single intramuscular injection of 1 ml of TroVax 10x. This dose will be given without IL-2. Then, every three to four weeks for four injections, TroVax will be given in the morning. These doses may be given in conjunction with IL-2. Immediately before each injection, blood will be drawn for immunological testing (100 ml). Before the injection, blood will also be drawn for clinical pathology (full blood count and clinical chemistry). A urine sample will be obtained for urinalysis for protein and blood.

IL-2 will be given intravenously (IV) in a dose of 600,000 IU/kg every eight hours for up to 15 injections in each cycle. The first dose will be given in the afternoon of the same day as the second TroVax injection. These cycles of TroVax and IL-2 will be repeated every 3-4 weeks depending upon patient tolerance and clinical response. Cycles of IL-2 will always commence in the afternoon after TroVax has been given in the morning. If IL-2 is not tolerated, it may be suspended but treatment with TroVax will be continued so long as it is well tolerated. TroVax may be given for up to three months (i.e. injection 5) to patients with progressive disease so long as no other anticancer treatment (i.e. chemotherapy, interferon alpha or radiotherapy) is considered indicated for them.

CT scans (chest abdomen, pelvis) will be obtained to restage the disease at weeks 9-10 and 15-16 (i.e. after two and four doses of IL-2 and/or 3 and 5 doses of TroVax).

A blood sample for immunological testing (100 ml) will be obtained three and eight weeks after the fifth TroVax injection (4 and 5 months).

Following the CT scan at 15-16 weeks patients will be followed at three monthly intervals, commencing at six months. Patients whose disease is progressing at this point may not be treated further with TroVax but may be kept on study and observed at three monthly intervals. Patients whose disease has stabilised or responded will be offered three further injections of TroVax at months 6, 9 and 12. Patients whose disease progresses or who experience serious or severe adverse events related to TroVax will stop treatment with TroVax but may be kept on study and reviewed at three monthly intervals. If the patient requires further treatment with established anticancer agents, these will be recorded in the CRF.

At each visit, from week 12 to month 12, regardless of disease status, blood will be obtained (prior to the injection of TroVax, if indicated) for clinical pathology, pituitary hormone screen, autoantibodies and immunological testing (100 ml). A urine sample will be obtained for urinalysis for protein and blood. The disease will be restaged using CT scans (chest abdomen, pelvis).

When TroVax is being administered, patients will return 3 weeks after each TroVax injection for immunological testing (100 ml).

After month 12, patients will return at three monthly intervals for a further 12 months. At each visit, the disease will be restaged using CT scans (chest abdomen, pelvis) in accordance with current institutional guidelines. Blood (100 ml) will be obtained for immunological testing, autoantibodies and pituitary function tests. A urine sample will be obtained for urinalysis for protein and blood. Patients, who at the end of this period, have stable or responding disease may be followed at three monthly intervals until disease progression occurs.

A Study of TroVax Vaccine Given in Conjunction With IL-2 for Treatment of Stage IV Renal Cell Cancer

Clinical Trial Phase II (Single Centre Study) : A Preliminary Study of the Safety, Immunogenicity, and Clinical Efficacy of TroVax Given in Conjunction With Interleukin 2 (IL-2) in the Treatment of Stage IV Renal Cell Cancer

incidence of adverse events, laboratory tests and occurrence of dose limiting toxicity

positive antibody response for the vector (MVA) / tumour (5T4)

Columbia University

Symptoms and General Pathology

Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

Neoplastic Processes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Hematinics

Liver Extracts

Robert Hawkins, MD, Prof

This study will test the safety and efficacy of TroVax in patients undergoing surgical resection of colorectal cancer with liver metastases.

TroVax potentially works by encouraging the immune system to react against the 5T4 protein on the surface of bowel cancer cells. The immune system is then able to recognise 5T4 and kill cells that carry it. The hope is that if tumour cells started to grow again after the main tumour has been surgically removed, the immune system would be able to find and destroy them.

Treatment of metastatic colorectal cancer depends on the site of disease. The prognosis for patients is poor although cure can be obtained if disease is localised and operable. Patients with metastatic disease confined to the liver may achieve a cure rate of between 20% and 60% if these metastases are resited, but there is a risk that micrometastatic disease will persist post-operatively.

TroVax consists of a highly attenuated vaccinia virus (modified vaccinia Ankara) containing the human tumour associated antigen ST4.

The human oncofetal antigen 5T4 a surface glycoprotein expressed by placental tissue, but also by a wide range of human carcinomas including most colorectal and renal carcinomas. 5T4 exhibits only low level expression in normal tissue and is thus a suitable target for immune therapy of cancer.

This study will evaluate for the first time in man the immunological effects of the TroVax vaccine locally within a target tumour and in peripheral blood. Tolerability of the vaccine will also be assessed.

Patients receive 2 intramuscular injections of TroVax at a 2 week interval followed by surgery 10 days later. Two further vaccinations are given at 4 and 8 weeks after surgery. Patients who show a response to the first four vaccinations are given 2 additional vaccinations 20 and 28 weeks post surgery.

Effect of TroVax in Patients Having Colorectal Cancer With Liver Metastases Removed

A Phase 2 Study Immunologically Evaluating 5T4-MVA (TroVax) in Patients Undergoing Surgical Resection of Colorectal Liver Metastases

Cancer Research UK

Prostatic Neoplasms

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Prostatic Diseases

Androgens

Hormones

Molgramostim

Sargramostim

Immunologic Factors

11 Intramuscular injection of TroVax® over 45 weeks. A single dose of 5 x 108 pfu/ml, will be given by an intramuscular injection into the deltoid muscle of the upper arm.

168 subcutaneous GM-CSF injections over 45 weeks. Administered every day as a subcutaneous injection at a dose of 250mcg/m2/d (maximum 500 mcg) in weeks 1 and 2 of each 28 day cycle (total of 14 days per cycle with a total of 12 cycles).

GM-CSF

Robert J Amato, DO

To evaluate the efficacy and safety of Trovax and GM-CSF in patients with prostate cancer.

Prostate cancer is the second leading cause of cancer death in American men. Hormonal ablation, in the form of medical or surgical castration is the cornerstone of management for metastatic prostate cancer however, treatment options for a patient in whom androgen ablation fails are limited. Second-line hormonal agents are generally associated with low response rates and no documented survival benefit.

Historically, chemotherapy was not considered to have significant activity in hormone refractory prostate cancer (HRPCa). This view has changed within the past 10 years, partly because of the availability of prostate-specific antigen (PSA) measurements to monitor tumor burden. Although it seems that chemotherapy, either as a single agent or combination of agents may lead to clinical responses, reduction in PSA measurements, pain control, or improved quality of life, no benefit in overall survival has been definitively proven. The current standard of care for the treatment of metastatic prostate cancer is hormone therapy (androgen blockade).3,4 When this strategy is no longer effective, few good treatment options are left. For this reason, prostate cancer research has aimed to identify new therapeutic modalities to increase the impact of these parameters as well as prolong patient survival.

A total of 24 men with prostate cancer ranging from non-metastatic rising PSA only disease to bony metastatic disease will be enrolled in the study. All patients will have failed androgen treatment and at least one prior taxane chemotherapy or have refused chemotherapy.

Out of the 24 patients, 12 patients will be treated using TroVax® and 12 will be treated using TroVax® plus GM-CSF.

Activity of TroVax® Alone vs. TroVax® Plus GM-CSF in Patients With Prostate Cancer

A Phase II Trial to Assess the Activity of TroVax® Alone vs. TroVax® Plus Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) in Patients With Progressive Hormone Refractory Prostate Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
TroVax Renal Immunotherapy Survival Trial	NCT00397345	Clear Cell Rena...	Trovax Placebo Standard of car...	18 Years -	Oxford BioMedica
Safety and Biological Activity of TroVax® Vaccine Given With IL-2 in Renal Cell Carcinoma	NCT00325507	Carcinoma, Rena...	TroVax IL-2	18 Years -	Oxford BioMedica
A Study of TroVax Vaccine Given in Conjunction With IL-2 for Treatment of Stage IV Renal Cell Cancer	NCT00083941	Carcinoma, Rena...	TroVax Interleukin-2	18 Years -	Oxford BioMedica
Effect of TroVax in Patients Having Colorectal Cancer With Liver Metastases Removed	NCT00259844	Colorectal Neop...	TroVax	18 Years -	Cancer Research UK
Activity of TroVax® Alone vs. TroVax® Plus GM-CSF in Patients With Prostate Cancer	NCT00448409	Prostatic Neopl...	TroVax GM-CSF	18 Years -	The Methodist Hospital Research Institute
Effect of TroVax in Patients Having Colorectal Cancer With Liver Metastases Removed	NCT00259844	Colorectal Neop...	TroVax	18 Years -	Cancer Research UK

Spots Global Cancer Trial Database for trovax

Every month we try and update this database with for trovax 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 trovax

Every month we try and update this database with for trovax 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 trovax 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.