Pharmacy and Poisons Board
Protocol No: ECCT/13/07/04 Date of Protocol: 07-08-2012
Study Title:

A Randomized Comparison of Three Regimens of Chemotherapy with Compatible Antiretroviral Therapy for Treatment of Advanced AIDS-KS in Resource-Limited Settings

Title remains the same.

Study Objectives:

To compare the effects of randomized treatment on serum levels of inflammatory cytokines and/or molecules associated with angiogenesis.

To determine whether serum levels of cytokines and angiogenesis-associated molecules are associated with clinical response, immunological response (assessed by measuring CD4+ lymphocyte cell count), virological responses (assessed by measurement of HIV-1 and HHV8 viral load), and the development of IRIS.

 

 
Laymans Summary:

Acquired immuno deficiency syndrome related Kaposi’s sarcoma (AIDS-KS) occurs in
persons who are co-infected with HIV-1 and human herpes virus 8 (HHV-8 or KSHV).
Although highly active ART alone may lead to regression of limited-stage (T0) AIDSKS,
patients with advanced or rapidly progressive AIDS-KS are usually treated with
concomitant ART and chemotherapy. While a number of single chemotherapeutic agents
and drug combinations have proven effective in inducing regression of AIDS-KS, the
most effective regimens to use in combination with ART have not been well defined,
because many of the drugs used to treat KS were tested prior to the introduction of highly
active ART. Current Kenya ministry of health guidelines recommends the use of
vincristine and bleomycin with or without non liposomal doxorubicin. Because there is
no single chemothepeutic agent that has proven superior to others in combination with
ART and because availability of chemotherapeutic agent and the current standards for
treatment of AIDS KS differ in different resource limited settings, a randomized
comparison of PTX with either BV or oral ET is justified. The primary objective of this
study is to compare the clinical efficacy of two regimens, oral etoposide plus ART and
Bleomycin vincristin plus ART, to Paclitaxel plus ART for initial treatment of advanced
stage AIDS-KS. This is a prospective, randomized, active- controlled clinical trial. The
participants (male and female) must be 18 years and above with documented HIV-1
infection and must have a biopsy diagnostic of KS. They must not have used radiation
and chemotherapy treatment for KS, are currently not receiving ART or are pregnant and
they must also have advanced KS stage T1. At study entry participants will be
randomized 1:1:1 to oral etoposide (ET) plus antiretroviral therapy (arm 1A), bleomycin
and vincristine (arm 1B) plus ART, or Paclitaxel(PTX) plus ART (arm 1C). The Kericho
site will recruit 40-60 participants from Kericho District hospital and nearby health
facilities. The site accrual will be approximately 4 participants per month; hence
estimated duration of accrual of 10-15 months. Participants will be followed for 5-7
years depending on the randomization or assignment to the last step they enter. Scant data
is available to guide the optimal use of chemotherapy in combination with ART. Results
from this study will try to define the potential benefits of adjunctive chemotherapy in
treatment of advanced
KS in the era of HAART and will inform on treatment guidelines.
Abstract of Study:

Acquired immuno deficiency syndrome related Kaposi’s sarcoma (AIDS-KS) occurs in
persons who are co-infected with HIV-1 and human herpes virus 8 (HHV-8 or KSHV).
Although highly active ART alone may lead to regression of limited-stage (T0) AIDSKS,
patients with advanced or rapidly progressive AIDS-KS are usually treated with
concomitant ART and chemotherapy. While a number of single chemotherapeutic agents
and drug combinations have proven effective in inducing regression of AIDS-KS, the
most effective regimens to use in combination with ART have not been well defined,
because many of the drugs used to treat KS were tested prior to the introduction of highly
active ART. Current Kenya ministry of health guidelines recommends the use of
vincristine and bleomycin with or without non liposomal doxorubicin. Because there is
no single chemothepeutic agent that has proven superior to others in combination with
ART and because availability of chemotherapeutic agent and the current standards for
treatment of AIDS KS differ in different resource limited settings, a randomized
comparison of PTX with either BV or oral ET is justified. The primary objective of this
study is to compare the clinical efficacy of two regimens, oral etoposide plus ART and
Bleomycin vincristin plus ART, to Paclitaxel plus ART for initial treatment of advanced
stage AIDS-KS. This is a prospective, randomized, active- controlled clinical trial. The
participants (male and female) must be 18 years and above with documented HIV-1
infection and must have a biopsy diagnostic of KS. They must not have used radiation
and chemotherapy treatment for KS, are currently not receiving ART or are pregnant and
they must also have advanced KS stage T1. At study entry participants will be
randomized 1:1:1 to oral etoposide (ET) plus antiretroviral therapy (arm 1A), bleomycin
and vincristine (arm 1B) plus ART, or Paclitaxel(PTX) plus ART (arm 1C). The Kericho
site will recruit 40-60 participants from Kericho District hospital and nearby health
facilities. The site accrual will be approximately 4 participants per month; hence
estimated duration of accrual of 10-15 months. Participants will be followed for 5-7
years depending on the randomization or assignment to the last step they enter. Scant data
is available to guide the optimal use of chemotherapy in combination with ART. Results
from this study will try to define the potential benefits of adjunctive chemotherapy in
treatment of advanced
KS in the era of HAART and will inform on treatment guidelines.
6
Acquired immunodeficiency syndrome related Kaposi’s sarcoma (AIDS-KS) occurs in
persons who are co-infected with HIV-1 and human herpes virus 8 (HHV-8 or KSHV).
Although highly active ART alone may lead to regression of limited-stage (T0) AIDSKS,
patients with advanced or rapidly progressive AIDS-KS are usually treated with
concomitant ART and chemotherapy. While a number of single chemotherapeutic agents
and drug combinations have proven effective in inducing regression of AIDS-KS, the
most effective regimens to use in combination with ART have not been well defined,
because many of the drugs used to treat KS were tested prior to the introduction of highly
active ART. Current Kenya ministry of health guidelines recommends the use of
vincristine and bleomycin with or without non-liposomal doxorubicin. Because there is
no single chemotherapeutic agent that has proven superior to others in combination with
ART and because availability of chemotherapeutic agent and the current standards for
treatment of AIDS KS differ in different resource limited settings, a randomized
comparison of PTX with either BV or oral ET is justified. The primary objective of this
study is to compare the clinical efficacy of two regimens, oral etoposide plus ART and
bleomycin vincristine plus ART, to Paclitaxel plus ART for initial treatment of advanced
stage AIDS-KS. This is a prospective, randomized, active- controlled clinical trial. The
participants (male and female) must be 18 years and above with documented HIV-1
infection and must have a biopsy diagnostic of KS. They must not have used radiation
and chemotherapy treatment for KS, are currently not receiving ART or are pregnant and
they must also have advanced KS stage T1. At an interim review in March 2016, the
DAIDS Co-infections and Complications Data Safety Monitoring Board (CCDSMB)
found that the ET plus ART arm was less effective than the paclitaxel (PTX) plus ART
arm. Per the CCDSMB recommendation, enrollment into this arm and all initiation of ET
in subsequent steps were discontinued in March 2016. At study entry participants will be
randomized 1:1 to bleomycin and vincristine (arm 1B) plus ART, or Paclitaxel (PTX)
plus ART (arm 1C). The Kericho site will recruit 40-60 participants from Kericho
District hospital and nearby health facilities. The site accrual will be approximately 4
participants per month; hence estimated duration of accrual of 10-15 months. Participants
who received etoposide (ET) while on study will be followed for 144 weeks after
beginning the last cycle of ET. Participants who did not receive ET while on study, who
are randomized only to Step 1 and who do not enter Step 2 or 3 will be followed for 96
weeks from Step 1 entry. Participants who did not receive ET who are randomized to
Step 2 and/or 3 will be followed for 48 weeks after entry into the last step that they enter.
Scant data is available to guide the optimal use of chemotherapy in combination with
ART. Results from this study will try to define the potential benefits of adjunctive
chemotherapy in treatment of advanced KS in the era of HAART and will inform on
treatment guidelines.