## Protocol Section
### Identification Module
**NCT ID:** NCT00444379

**Acronym:** ARKS

**Brief Title:** Anti-Retrovirals for Kaposi's Sarcoma

**Official Title:** A Randomized Comparison of Protease Inhibitor-based Versus Non-nucleoside Reverse Transcriptase Inhibitor-based Antiretroviral Therapy for Initial Treatment of Individuals With AIDS-related Kaposi's Sarcoma in Sub-Saharan Africa

#### Organization Study ID Info
**ID:** NIH/NCI Grant #: R01 CA119903
#### Organization
**Class:** OTHER
**Full Name:** University of California, San Francisco
### Status Module
#### Completion Date
**Date:** 2012-07

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2014-08-20

**Type:** ESTIMATED

**Last Update Submit Date:** 2014-08-19

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2012-02

**Type:** ACTUAL

#### Start Date
**Date:** 2007-04

**Status Verified Date:** 2014-08

#### Study First Post Date
**Date:** 2007-03-07
**Type:** ESTIMATED
**Study First Submit Date:** 2007-03-06
**Study First Submit QC Date:** 2007-03-06
### Sponsor Collaborators Module

#### Collaborators

**Class:** NIH

**Name:** National Institutes of Health (NIH)

**Class:** INDUSTRY

**Name:** Gilead Sciences

**Class:** INDUSTRY

**Name:** Abbott

**Class:** INDUSTRY

**Name:** Merck Sharp & Dohme LLC

#### Lead Sponsor

**Class:** OTHER

**Name:** University of California, San Francisco

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The primary purpose of this study is to determine whether a protease inhibitor-based antiretroviral regimen is more efficacious than a non-nucleoside reverse transcriptase inhibitor-based antiretroviral regimen in promoting the regression of KS tumor burden in persons with AIDS-related KS in Africa.

**Detailed Description:** With the advent of the HIV epidemic, Kaposi's sarcoma (KS) is now the most common adult cancer in many parts of sub-Saharan Africa. In HIV-infected patients with KS in developed settings, the initiation of highly active anti-retroviral therapy (HAART) has been associated with regression of the tumor, in many but not all cases, even in the absence of conventional chemotherapy. However, it is not known which specific antiretroviral drugs or regimens are critical to convey HAART's anti-KS effect. In particular, it is not known whether the anti-KS effects of protease inhibitors (PI) in vitro and in animal models translate into improved clinical outcomes as compared to non-PI-based HAART regimens. To address this, we will determine whether a PI-based HAART regimen (lopinavir/ritonavir plus emtricitabine/tenofovir) is superior to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen (efavirenz plus emtricitabine/tenofovir) in promoting the regression of KS tumor burden in persons with AIDS-related KS in sub-Saharan Africa. We will enroll 224 patients with AIDS-related KS in Kampala, Uganda, randomly assign them to either a PI-based HAART or an NNRTI-based HAART regimen, and observe them for one year to determine the response in their KS to therapy.

### Conditions Module

**Conditions:**

- Kaposi's Sarcoma

- HIV Infections

**Keywords:**

- Kaposi's sarcoma

- KSHV

- AIDS

- HHV-8

- treatment naive

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 224

**Type:** ACTUAL

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** PI-based HAART regimen (lopinavir/ritonavir plus emtricitabine/tenofovir)

**Intervention Names:**

- Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir

**Label:** PI-based HAART regimen

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen (efavirenz plus emtricitabine/tenofovir)

**Intervention Names:**

- Drug: Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir

**Label:** non-nucleoside reverse transcriptase inhibitor

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- PI-based HAART regimen

- non-nucleoside reverse transcriptase inhibitor

**Description:** Lopinavir/ritonavir 200/50mg plus Emtricitabine/Tenofovir 200/300mg versus Efavirenz 600mg plus Emtricitabine/Tenofovir 200/300mg

**Name:** Lopinavir/ritonavir plus Emtricitabine/Tenofovir versus Efavirenz plus Emtricitabine/Tenofovir

**Other Names:**

- Lopinavir/ritonavir Aluvia (ALUABT)

- Efavirenz Stocrin (EFVBMM)

- Emtricitabine/Tenofovir Truvada (TRUGLD)

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** survival

**Measure:** Blinded assessment of the change in the burden of KS lesions

#### Secondary Outcomes

**Measure:** CD4+ T cell count and HIV plasma HIV RNA levels

**Measure:** KSHV DNA levels in saliva and blood

**Measure:** Humoral and cellular KSHV immune response markers

**Measure:** Quality-of-life assessment

**Measure:** Incidence of Kaposi's sarcoma-associated Immune Reconstitution Inflammatory Syndrome (KS-IRIS)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Age 18 years or older
* HIV-1 infection
* No prior antiretroviral therapy of any duration, including prior use to prevent perinatal transmission within prior six months.
* No prior chemotherapy or radiotherapy for KS
* Presence of Kaposi's sarcoma, documented by biopsy by the Pathology Department at Mulago Hospital, with at least one mucocutaneous lesion (including oral or genital mucosal lesions), each at least 0.6 x 0.6 cm in perpendicular diameters.
* Laboratory values obtained within 21 days prior to randomization: absolute neutrophil count equal to or more than 1000/mm3; hemoglobin \> 9.0 g/dL; platelet count \> 50,000/mm3; creatinine \< 2 times upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 times ULN; and alkaline phosphatase and total bilirubin \< 2 times ULN.
* In women, negative urine pregnancy test within 28 days of randomization and just before randomization.
* If a woman of child-bearing potential (i.e., not yet reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation), must be willing to use at least two of the following methods of contraception, to be provided by the study: condoms (male or female), IUD, or hormone-based therapy, e.g., contraceptive pills, Norplant or Depo-Provera.
* Candidate currently resides within Uganda and does not intend to relocate away from current geographical area of residence for the duration of study participation.
* Karnofsky performance score of 70 or more

Exclusion Criteria:

* Extensive degree of mucocutaneous KS, which would typically require chemotherapy or radiotherapy. This is defined by any of the following:

  * One or more bulky cutaneous lesions, defined as at least 5.0 cm in greatest diameter across the surface of the skin and at least 3 cm in height
  * One or more mucocutaneous lesions exhibiting ulceration
  * One or more oral lesions that interfere with swallowing
* Suggestion of pulmonary or gastrointestinal visceral KS, as evidenced by any of the following:

  * Abnormal chest x-ray within 21 days prior to randomization which is otherwise unexplained, unless the x-ray is unchanged compared with at least 60 days earlier
  * Positive occult blood stool testing within 21 days prior to randomization or history of overt bleeding from the mouth or rectum in the 21 days prior to randomization
* Facial lymphedema or lymphedema in any other body region which causes symptoms (e.g., pain) or functional disability (e.g., any less than 85% active range of motion in a large joint)
* Evidence of currently active, untreated opportunistic infection or malignancy (not including Kaposi's sarcoma); or unexplained temperature which is \> 38.5 degrees C
* Use of drugs, within the prior 28 days, contraindicated while taking lopinavir/ritonavir or efavirenz because of effects on the cytochrome P450 system. These include propafenone, astemizole, terfenadine, rifampin, rifapentine, ergot derivatives, cisapride, lovastatin, simvastatin, pimozide, midazolam, and triazolam.
* Active drug or alcohol use that, in the investigators' opinion, would interfere with study participation
* Breastfeeding

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Kampala

**Country:** Uganda

**Facility:** Infectious Diseases Institute, Mulago Hospital

#### Overall Officials

**Official 1:**

**Affiliation:** University of California, San Francisco

**Name:** Dr. Jeffrey N Martin, MD, MPH

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** MRC/UVRI and LSHTM Uganda Research Unit

**Name:** Dr. Edward K Mbidde, MBChB, MMed

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### See Also Links

**Label:** Medline Plus- Health Information

**URL:** http://www.nlm.nih.gov/medlineplus/kaposissarcoma.html

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000018204

- Term: Neoplasms, Connective and Soft Tissue

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000007239

- Term: Infections

- ID: D000014777

- Term: Virus Diseases

- ID: D000006566

- Term: Herpesviridae Infections

- ID: D000004266

- Term: DNA Virus Infections

- ID: D000009383

- Term: Neoplasms, Vascular Tissue

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M3522

- Name: Acquired Immunodeficiency Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M18250

- Name: HIV Infections

- Relevance: LOW

- As Found: Unknown

- ID: M15327

- Name: Sarcoma

- Relevance: HIGH

- As Found: Sarcoma

- ID: M15332

- Name: Sarcoma, Kaposi

- Relevance: HIGH

- As Found: Kaposi's Sarcoma

- ID: M20350

- Name: Neoplasms, Connective and Soft Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M17522

- Name: Virus Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9643

- Name: Herpesviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M7442

- Name: DNA Virus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M12328

- Name: Neoplasms, Vascular Tissue

- Relevance: LOW

- As Found: Unknown

- ID: T5284

- Name: Soft Tissue Sarcoma

- Relevance: HIGH

- As Found: Sarcoma

- ID: T3199

- Name: Kaposi Sarcoma

- Relevance: HIGH

- As Found: Kaposi's Sarcoma

### Condition Browse Module - Meshes

- ID: D000012514

- Term: Sarcoma, Kaposi

- ID: D000012509

- Term: Sarcoma

### Intervention Browse Module - Ancestors

- ID: D000017320

- Term: HIV Protease Inhibitors

- ID: D000084762

- Term: Viral Protease Inhibitors

- ID: D000011480

- Term: Protease Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000019380

- Term: Anti-HIV Agents

- ID: D000044966

- Term: Anti-Retroviral Agents

- ID: D000000998

- Term: Antiviral Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000065692

- Term: Cytochrome P-450 CYP3A Inhibitors

- ID: D000065607

- Term: Cytochrome P-450 Enzyme Inhibitors

- ID: D000018894

- Term: Reverse Transcriptase Inhibitors

- ID: D000019384

- Term: Nucleic Acid Synthesis Inhibitors

- ID: D000065688

- Term: Cytochrome P-450 CYP2C9 Inhibitors

- ID: D000065689

- Term: Cytochrome P-450 CYP2C19 Inhibitors

- ID: D000065695

- Term: Cytochrome P-450 CYP2B6 Inducers

- ID: D000065693

- Term: Cytochrome P-450 Enzyme Inducers

- ID: D000065701

- Term: Cytochrome P-450 CYP3A Inducers

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M21394

- Name: Ritonavir

- Relevance: HIGH

- As Found: Left

- ID: M296

- Name: Tenofovir

- Relevance: HIGH

- As Found: 1000

- ID: M294

- Name: Emtricitabine

- Relevance: HIGH

- As Found: Sampling

- ID: M29837

- Name: Lopinavir

- Relevance: HIGH

- As Found: Mg/kg/day

- ID: M20935

- Name: Reverse Transcriptase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M340137

- Name: Efavirenz

- Relevance: HIGH

- As Found: See

- ID: M19609

- Name: HIV Protease Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M14343

- Name: Protease Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M25428

- Name: Anti-Retroviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M448

- Name: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

- Relevance: HIGH

- As Found: Scaling

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M21350

- Name: Anti-HIV Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M30564

- Name: Cytochrome P-450 CYP3A Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M30537

- Name: Cytochrome P-450 Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000019438

- Term: Ritonavir

- ID: D000061466

- Term: Lopinavir

- ID: D000068698

- Term: Tenofovir

- ID: D000068679

- Term: Emtricitabine

- ID: D000069480

- Term: Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

- ID: C000098320

- Term: Efavirenz

### Misc Info Module

- Version Holder: 2024-05-24
