Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle.

NOX66 treatment given to 3 cohorts of 4 patients as 1 of 3 doses, 400mg, 800mg and 1200 mg.

Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.

NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle.

NOX66 dose will be either one of 3 doses 400mg, 800mg and 1200 mg based on interim analyses of safety data and tumour response at WEEK 6 of 3 dose cohorts of 12 total patients. The Safety Steering Committee will inform on dose for cohort expansion.

Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.

NOX66

Irradiation Therapy

Marinella Messina, PhD

The study is intended as a Proof of Concept and dose confirmation study. The primary objective of this study is to observe safety and tolerability of idronoxil (NOX66) in combination with radiotherapy (at palliative doses) in patients with metastatic castrate-resistant prostate cancer (CRPC) and to confirm dose in order to progress to Phase 2/3.

This study will investigate three escalating doses of NOX66 in combination with palliative dose of radiation therapy to establish safety profile and / or obtain efficacy signals and to determine the optimal dose for future radiation therapy combination studies.

The key hypotheses to be tested in this study are:

1. That NOX66 can be safely added to palliative dose radiation therapy.
2. That NOX66 may sensitise tumours to palliative doses of radiation therapy
3. That NOX66 in combination with radiation therapy may trigger or augment an abscopal effect

Participants will have a minimum of 1 symptomatic lesion amenable to radiation therapy.

Radiation therapy will be delivered at a 20Gy dosage over 5 fractions. NOX66 will be taken on 13 consecutive days starting 1 day prior to radiotherapy.

The response of irradiated and non-irradiated target tumour lesions will be measured by CT/MRI scan and RECIST1.1 criteria at three time points post treatment. Pain response will be evaluated using the Brief Pain Inventory-Short Form (BPI-SF) instrument at five time points post treatment.

Patients will be suitable for the study as they become indicated for palliative radiation therapy for management of their cancer.

This study will enrol up to 24 patients in 3 NOX66 dose level cohorts of 4 patients (n=12) and an expansion cohort of 12 patients. Dose escalation decisions will be based on patients who experience adverse events directly related to NOX66 treatment.

Following the review of accumulated safety data, disease status and treatment efficacy signals at WEEK 6 for the first 12 patients, the Study Steering Committee will determine the dose at which to continue treatment for the expansion patient Cohort 4 in the study. A further 12 patients will be recruited at this dose level.

Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer

NOX66 and Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer - a Phase 1b Proof of Concept and Dose Confirmation Study

De-identified individual participant data for primary and secondary outcome measure will be made available within 12 months after study completion.

Safety will be assessed through reported incidence of treatment emergent adverse events (AEs), including SAEs, dose limiting toxicities, AEs leading to withdrawal, events of at least CTCAE Version 4.03 Grade 2 in severity. Treatment emergent AEs are those with an onset on or after the initiation of therapy. Timepoints for AE /SAE assessment are Day 2 (start of radiation therapy treatment and one day after start of NOX66 treatment), Day 6, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.

Other safety endpoints include laboratory results which are assessed at Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.

Further safety endpoints include laboratory results and ECG findings which are assessed Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.

RECIST response in target irradiated and non-irradiated lesions based on radiographic CT/MRI scan. RECIST 1.1 criteria are Complete Response (CR), Partial Response (PR), Stable Disease(SD) and Progressive Disease (PD)

RECIST 1.1 assessment of response in Non-target lesions

Overall RECIST 1.1 response based on combined assessment criteria for target, non-target and new lesions lesions as Complete Response (CR), Partial Response (PR), Stable Disease(SD) and Progressive Disease (PD)

Change from baseline in pain score based on responses to BPI-SF

Noxopharm Limited

Blood and Lymph Conditions

Immune System Diseases

Infections

Rare Diseases

Lymphoma

Acquired Immunodeficiency Syndrome

HIV Infections

Hodgkin Disease

Lymphoma, AIDS-Related

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Lymphoma AIDS Related

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

Etoposide

Cytarabine

Cyclophosphamide

Carboplatin

Rituximab

Melphalan

Cyclosporine

Cyclosporins

Ifosfamide

Lenograstim

Etoposide phosphate

Carmustine

Isophosphamide mustard

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Non Hodgkin's Lymphoma patients treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF.

Patients with Hodgkin's lymphoma treated with cyclosphosphamide, carmustine, etoposide, peripheral blood stem cell transplantation and G-CSF.

Non Hodgkin's Lymphoma patients infected with HIV, treated with cyclophosphamide, total body irradiation therapy, peripheral blood stem cell transplantation and G-CSF.

Patients with non Hodgkin's lymphoma ineligible to receive total body irradiation because of prior radiation and are not candidates for high dose cyclophosphamide will be treated with carmustine, etoposide, cytarabine, and melphalan followed by peripheral blood stem cell transplantation and G-CSF (called BEAM conditioning).

carmustine

NHL with radiation: Cyclophosphamide 60 mg/kg intravenous (IV) over two hours daily x 2 days.

HL without radiation: Cyclophosphamide, Days - 6 through -3, 1.5 gm/m\^2 over 2 hours daily x 4 days.

Cyclophosphamide will be dosed based on actual body weight (ABW) unless the patient is 20% or more of ideal body weight (IBW). If more than 20% of ideal body weight, an adjusted ideal body weight (AIBW) will be used for dosing.

cyclophosphamide

NHL without radiation and cyclophosphamide: Etoposide 100 mg/m2 IV over 2 hours twice daily on Day -5 through -2.

HL without radiation: 150 mg/m\^2 intravenously over 4 hours every 12 hours for 6 total doses on Days -6 through -4.

etoposide

Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF alone (filgrastim) or using ifosfamide/carboplatin/etoposide and with or without rituximab. Leukapheresis is to begin on Day 5.

peripheral blood stem cell transplantation

Patients undergo total body irradiation (TBI) twice daily on days -4 to -1.

* \> 1000 cGy to whole lung, kidney, or abdominal bath.
* \> 3000 cGy to spinal cord, myocardium, mediastinum, lumbar periaortic lymph nodes.
* \> 3600 cGy to whole brain.

irradiation therapy

Day 5: Begin G-CSF 5μg/kg/day subcutaneously (SQ) rounded to the nearest vial size.

Continue G-CSF until absolute neutrophil count (ANC) \> 1500/μl x 3 consecutive days.

If ANC falls \<1000/μL, restart G-CSF.

G-CSF

100 mg/m\^2 over one hour BID on days -6 through -2 of BEAM conditioning regimen.

Veronika Bachanova, MD

RATIONALE: Drugs used in chemotherapy, such as ifosfamide, etoposide, and carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the patient's bone marrow to the blood so they can be collected and stored for peripheral stem cell transplant. Giving more chemotherapy, such as cyclophosphamide, carmustine, and etoposide, and total-body irradiation prepares the patient's bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy. More radiation therapy is given after transplant to kill any remaining cancer cells.

PURPOSE: This phase II trial is studying how well autologous peripheral stem cell transplant works in treating patients with non-Hodgkin's lymphoma or Hodgkin's lymphoma.

OBJECTIVES:

Primary

* Determine the disease-free survival and overall survival of patients with non-Hodgkin's or Hodgkin's lymphoma treated with autologous peripheral blood stem cell transplantation (PBSCT).
* Verify the safety and efficacy of autologous PBSCT in patients with HIV disease and relapsed lymphoma.

Secondary

* Evaluate immune reconstitution in HIV-positive patients undergoing autologous PBSCT and compare to immune reconstitution in HIV-negative patients.
* Predict the adequacy of peripheral blood stem cell (PBSC) harvest prior to flow analysis of a PBSC yield.
* Determine the time to engraftment for neutrophils and platelets.

OUTLINE:

* Peripheral blood stem cell (PBSC) mobilization with filgrastim (G-CSF) alone: Patients not requiring further disease reduction receive G-CSF subcutaneously (SC) once daily on days 1-8. Patients undergo PBSC collection by leukapheresis on days 5-8. Patients who do not adequately mobilize with G-CSF alone proceed to chemo-mobilization.
* Chemo-mobilization: Patients requiring further disease reduction receive 1 of 2 chemo-mobilization regimens.

  * Patients with CD20+ non-Hodgkin's lymphoma (NHL) or lymphocyte predominant Hodgkin's lymphoma: Patients receive rituximab intravenously (IV) over 6-8 hours on day 1, ifosfamide IV over 2 hours and etoposide IV over 30 minutes on days 2-4, and carboplatin IV over 1 hour on day 2. Patients receive G-CSF SC once daily beginning on day 5 and continuing until leukapheresis is completed. Patients undergo PBSC collection by leukapheresis on days 12-15.
  * All other patients: Patients receive ifosfamide IV over 2 hours and etoposide IV over 30 minutes on days 1-3 and carboplatin IV over 1 hour on day 1. Patients receive G-CSF SC once daily beginning on day 4 and continuing until leukapheresis is completed. Patients undergo PBSC collection by leukapheresis on days 12-15.
* Autologous PBSC transplantation (PBSCT) (Patients with NHL undergoing irradiation): Patients receive cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total body irradiation (TBI) twice daily on days -4 to -1. Patients undergo autologous PBSCT on day 0. Patients receive G-CSF SC once daily beginning on day 5 and continuing until blood counts recover.
* Autologous PBSCT (Patients with Hodgkin's lymphoma or NHL not undergoing irradiation and cyclophosphamide): Patients receive camustine IV over 2 hours on days -6, etoposide IV over 2 hours twice daily on days -5 to -2, and melphalan over 1 hour on day -1. Patients undergo autologous PBSCT on day 0. Patients receive G-CSF SC once daily beginning on day 5 and continuing until blood counts recover.
* Autologous PBSC transplantation (PBSCT) (Patients with HL not undergoing irradiation): Patients receive cyclophosphamide IV over 2 hours on days -6 to -3, camustine IV over 2 hours on day -6, and etoposide IV over 4 hours twice daily on days -6 to -4. Patients undergo autologous PBSCT on day 0. Patients receive G-CSF SC once daily beginning on day 5 and continuing until blood counts recover.
* Post-transplant irradiation: Patients undergo post-transplant irradiation beginning on day 28. Persisting nodal masses ≥ 2 cm are treated with additional localized external beam irradiation.
* Post-transplant Rituximab therapy: patients with CD20+ NHL may undergo Rituximab maintenance starting between day +45 and +90 and being repeated at day +180 ± 14 days.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.

Autologous Peripheral Stem Cell Transplant in Treating Patients With Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma

Autologous Peripheral Blood Stem Cell Transplant for Patients With Lymphoma

Progression is defined using the Response Criteria for Non-Hodgkin's Lymphoma given by NCI Sponsored International Working Group.The definition is as follows:

At least a 50% increase from nadir of any previously identified abnormal node. Appearance of any new lesion during or at the end of therapy.

Progression is determined using Response Criteria for Non-Hodgkin's Lymphoma given by NCI Sponsored International Working Group.

Definition is as follows:

At least a 50% increase from nadir of any previously identified abnormal node. Appearance of any new lesion during or at the end of therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer	NCT03307629	Cancer	NOX66 Irradiation The...	18 Years -	Noxopharm Limited
Autologous Peripheral Stem Cell Transplant in Treating Patients With Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma	NCT00345865	Lymphoma	carmustine cyclophosphamid... etoposide peripheral bloo... irradiation the... G-CSF Cytarabine	- 75 Years	Masonic Cancer Center, University of Minnesota
Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer	NCT03307629	Cancer	NOX66 Irradiation The...	18 Years -	Noxopharm Limited

Spots Global Cancer Trial Database for irradiation therapy