Chemotherapy for Lung Cancer in HIV-positive Patients (CHIVA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01296113
Recruitment Status : Completed
First Posted : February 15, 2011
Last Update Posted : September 20, 2017
Information provided by (Responsible Party):
Intergroupe Francophone de Cancerologie Thoracique

Brief Summary:
This is a phase II, multicenter, non-randomized, open-label study evaluating the combination of pemetrexed plus carboplatin in HIV-positive patients with lung cancer.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Hiv-positive Drug: Chemotherapy Phase 2

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Detailed Description:

The use of tritherapy in developed countries starting in 1996 led to a considerable reduction in AIDS mortality due to opportunistic infections and AIDS-defining cancers. However, increased life expectancies were accompanied by a diversification of the causes of death in HIV-infected individuals. In France between 2000 and 2005, non-AIDS-defining mortality rose from 53% to 64%: non-AIDS-defining cancers (apart from hepatocellular carcinoma) had the highest mortality rates, increasing from 11% to 17% in 2005, followed by liver disease (15% in 2005), cardiovascular disease (8% in 2005) and suicide (5%). Among all cancer-related deaths (AIDS- and non-AIDS-defining), the proportion due to non-AIDS-defining cancers (apart from hepatocellular carcinoma) increased from 38% to 50% and lung cancer (LC) accounted for 65% of deaths. Many epidemiological studies have demonstrated an elevated risk of LC in HIV-infected individuals HIV-positive subjects are younger at diagnosis of LC than the general population (45 versus 62 years). In the most recent studies, adenocarcinoma comprised 70% of cases. The prognosis of LC is worse in HIV-positive individuals. Some authors suggest that these poor outcomes may be related to interactions and additive toxicities of the cytotoxic and antiretroviral drugs. It is also likely that the disease is particularly aggressive. In the general population with a PS of 0 or 1 and under 70 years of age, bitherapy improves survival as compared to monotherapy. Survival is higher when the doublet comprises a platin. Since HIV-positive subjects with LC tend to be young, it is logical to offer them the best treatment which has demonstrated efficacy in the general population. In comparison to cisplatin, carboplatin causes less vomiting, nephrotoxicity and neurotoxicity. Survival is very slightly higher with cisplatin, but this comes at the cost of greater toxicity. Carboplatin is better tolerated in subjects with PS=2 or who are over 70 years of age

The HIV-positive population is specific in that:

  • PS is more often altered but the subjects are young, which calls for a platin-based doublet.
  • HAART is essential and its absorption should not be compromised by repeated vomiting which is more severe with cisplatin.
  • Nephropathy occurs in 15-38% of cases; the causes are multifactorial and include the HIV virus itself and the antiretroviral drugs (Tenofovir®).
  • Peripheral neuropathy is frequently related to HIV or to the antiretroviral treatments (especially didanosine or stavudine (2010 YENI report)).
  • Premature ageing is seen in HIV-positive subjects; this exposes them to increased cardiovascular risk and a higher frequency of heart disease which can restrict the hyper-hydration required when using cisplatin.
  • In 2010, virtually all patients are treated on an ambulatory basis whereas in the past they would have been hospitalized. Carboplatin is administered in the day hospital of all the centers, but not cisplatin.
  • It is important to preserve an optimal quality of life during the first line of therapy in these patients whose life expectancy is such that very few will be eligible for a second round of therapy.

Scagliotti published a phase III trial comparing cisplatin plus pemetrexed with cisplatin plus gemcitabine in subjects < 70 years old with advanced-stage NSCLC. Overall survival was identical in both arms but the toxicity profile was in favor of the pemetrexed arm. The combination of first-line carboplatin plus pemetrexed has been evaluated in several phase II trials, particularly in subjects with a poor PS. In contrast to the taxanes or vinorelbine, for example, pemetrexed is not metabolized by CYP450, which facilitates its use in combination with protease inhibitors and NNRTI, which respectively inhibit or induce the CYP450 system.

Ancillary study BIO-IFCT-1001 will be made. Since the samples will be small, focus will be on the biomarkers associated with multiple or specific resistance to platinum salts or to pemetrexed, particularly those more specifically found in NSCLC of nonsquamous histology. Similarly, biomarkers for which IFCT pathologists have acquired an expertise will also be favored. This expertise mainly involves, on the one hand, detecting K-Ras mutations (15-25% of ADC) and RasSF1 methylation as well as TubIII expression by immunohistochemistry (IHC) and testing for mucosecretion by PAS diastase-resistant staining, and on the other hand, evaluating ERCC1 and/or MSH2 expression and thymidylate synthase (TS) expression by IHC.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial Evaluating the Efficacy and Safety of Carboplatin Plus Pemetrexed in Human Immunodeficiency Virus Positive (HIV+) Patients With Stage III (Not Amenable to Radiation or Inoperable) or Stage IV Nonsquamous Non Small Cell Lung Cancer
Study Start Date : May 2011
Actual Primary Completion Date : January 2016
Actual Study Completion Date : July 2017

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: A Drug: Chemotherapy

Pemetrexed + Carboplatin

On D1 of a 21-day cycle:

  • Pemetrexed 500 mg/m² IV in 10 minutes followed 30 minutes later by:
  • Carboplatin AUC 5 in 30 minutes in 100 ml sterile water or 5% glucose or physiological serum. The carboplatin dose will be calculated by the Calvert formula with a target AUC of 5 mg/mL.min as follows:

Carboplatin dose in mg = 5 x (GFR + 25) GFR is estimated according to the MDRD equation for creatinine clearance

• 4 cycles total

Primary Outcome Measures :
  1. Disease-Control rate after 4 cycles [ Time Frame: 3-weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • NSCLC histologically (highly recommended) and/or cytologically confirmed, stage III (non-irradiable or inoperable) or stage IV (according to 2009 TNM classification), with other than predominantly squamous histology
  • HIV seropositivity (previous or inaugural), irrespective of CD4 count or viral load
  • Presence of at least one measurable lesion (RECIST v1.1)
  • Subject having signed the informed consent form,
  • Subject who, in the investigator's opinion, will be able to comply with the requirements and constraints of the study
  • Age ≥ 18 years ≤ 75 years,
  • WHO performance status: 0, 1 or 2
  • Weight loss ≤ 10% of total body weight in the month before inclusion
  • Estimated life expectancy ≥ 1 month,
  • Covered by health insurance

Exclusion Criteria:

  • Bronchial cancer already treated (other than endoscopic deobstruction)
  • Cancer which is amenable to surgery or radiation (curative),
  • Squamous cell lung cancer or mixed small cell and non-small cell cancer, small cell lung cancer
  • Creatinine clearance (MDRD) < 45 mL/min
  • Severe hypersensitivity to any of the study products or excipients
  • Severe disease or uncontrolled systemic disease (unstable or decompensated respiratory disease, cardiac, hepatic or renal disease, uncontrolled opportunistic infection)
  • Significant abnormality in CBC-platelets (Hb <9 g/dL, PNN <1500 / mm3, platelets < 100,000 / mm3)
  • Significant abnormality in liver tests (AST, ALT > 3x ULN, and <5 in case of liver metastases),
  • Women of childbearing age without effective contraception; pregnant or breastfeeding women
  • Subject who cannot take vitamin B12, folic acid or corticosteroids
  • Diffuse interstitial pneumonia
  • Any geographical situation or psychological condition that precludes full understanding and compliance with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01296113

Centre Hospitalier du Pays d'Aix
Aix-en-Provence, France
Annemasse - CH
Ambilly, France, 74100
Annecy - CH
Annecy, France, 74374
Avignon - CH
Avignon, France
CH de la Côte Basque
Bayonne, France
CHU Besancon - Pneumologie
Besancon, France, 25000
Caen - CHU Côte de Nacre
Caen, France, 14000
CH Cahors
Cahors, France
Clermont-Ferrand, France
Colmar, France
CH Compiègne - Pneumologie
Compiègne, France
Créteil - CHI
Créteil, France, 94000
CHU Grenoble - pneumologie
Grenoble, France, 38000
Le Mans - Centre Hospitalier
Le Mans, France, 72000
Longjumeau, France
Hôpital de la Croix Rousse
Lyon, France
Hôpital Louis Pradel
Lyon, France
APHM - Hôpital Nord
Marseille, France, 13000
Montpellier - CHRU
Montpellier, France, 34295
Nevers - CH
Nevers, France, 58033
Centre Antoine Lacassagne
Nice, France
CHR d'Orléans La Source
Orléans, France
APHP - Hopital Tenon - Pneumologie
Paris, France, 75020
GH Paris Saint-Joseph
Paris, France
Hôpital Saint Antoine
Paris, France
Paris - Pitié-salpêtrière
Paris, France
Pau - CH
Pau, France, 64046
Centre François Magendie - hôpital du Haut-Lévèque
Pessac, France
HCL - Lyon Sud (Pneumologie)
Pierre Bénite, France, 69495
Reims - CHU
Reims, France, 51092
Rennes - CHU
Rennes, France, 35033
Saint Brieuc - CHG
Saint Brieuc, France, 22000
NHC - Pneumologie
Strasbourg, France, 63000
Suresnes - Hopital Foch
Suresnes, France, 92151
Thonon les bains - CH
Thonon les bains, France, 74200
Toulon - CHI
Toulon, France, 83000
CHU Toulouse - Pneumologie
Toulouse, France
Tourcoing - CH
Tourcoing, France, 59208
Tours - CHU
Tours, France, 37000
CH Valence
Valence, France
Sponsors and Collaborators
Intergroupe Francophone de Cancerologie Thoracique
Principal Investigator: Armelle LAVOLE, MD AP-HP, Hôpital Tenon

Additional Information:
Responsible Party: Intergroupe Francophone de Cancerologie Thoracique Identifier: NCT01296113     History of Changes
Other Study ID Numbers: IFCT-1001
First Posted: February 15, 2011    Key Record Dates
Last Update Posted: September 20, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
HIV Seropositivity
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors